GORE TAG THORACIC ENDOPROSTHESIS

P040043S051 · W. L. Gore & Associates, Inc. · MIH · Sep 10, 2013 · Cardiovascular

Device Facts

• Record ID: P040043S051
• Device Name: GORE TAG THORACIC ENDOPROSTHESIS
• Applicant: W. L. Gore & Associates, Inc.
• Product Code: MIH · Cardiovascular
• Decision Date: Sep 10, 2013
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic, Real-World Evidence

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
P040043S051 · Sep 10, 2013	GORE TAG THORACIC ENDOPROSTHESIS	W. L. Gore & Associates, Inc.	Peer-reviewed clinical literature reporting on endovascular treatment of chronic Type B dissections	The sponsor used a literature review of clinical outcomes for chronic Type B dissection patients to support the expansion of the device indication to include all lesions of the descending thoracic aorta, as clinical data for chronic dissections were not generated in the primary pivotal study.	Literature review; Chronic Type B dissection; Clinical outcomes; Real-world clinical cohorts

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Literature Review for Endovascular Treatment of Chronic Type B Dissections; Literature review of peer-reviewed clinical studies; Follow-up/Duration: 13 to 60 months	Patients with chronic Type B aortic dissections; Sample Size: 178 (combined across 5 studies); Number of Sites: Not applicable	Not applicable for this study	Operative mortality, mid-term survival

Indications for Use

The GORE® TAG® Thoracic Endoprosthesis is intended for endovascular repair of all lesions of the descending thoracic aorta, including: Isolated lesions in patients who have appropriate anatomy, including: Adequate iliac / femoral access Aortic inner diameter in the range of 16-42 mm ≥ 20 mm non-aneurysmal aorta proximal and distal to the lesion Type B dissections in patients who have appropriate anatomy, including: Adequate iliac / femoral access ≥ 20 mm landing zone proximal to the primary entry tear; proximal extent of the landing zone must not be dissected Diameter at proximal extent of proximal landing zone in the range of 16-42 mm

Device Story

Flexible, self-expanding nitinol wire frame stent graft covered with ePTFE/FEP; constrained on delivery catheter; deployed via femoral access. Used in OR by physicians for DTA lesions/dissections. Input: patient anatomy (CTA imaging). Operation: catheter-based delivery; deployment unlaces sleeve to expand graft against vessel wall. Output: physical exclusion of aortic lesion/entry tear. Benefit: minimally invasive repair of DTA pathologies; promotes false lumen thrombosis; restores true lumen perfusion. Clinical decision-making: used for acute complicated Type B dissection (malperfusion/rupture) or isolated lesions; requires post-op imaging for monitoring.

Clinical Evidence

Prospective, non-randomized, multi-center, single-arm pivotal study (TAG 08-01) of 50 subjects with acute complicated Type B dissection. Primary safety endpoint: 30-day all-cause mortality (met performance goal of 25%, p < 0.01). Primary effectiveness endpoint: 1-month primary entry tear exclusion (97.5% success). Secondary endpoints: false lumen thrombosis (73.3% complete at last follow-up), additional intervention rate (14%), aortic rupture (4%). Bench testing incorporated by reference from previous PMA supplements.

Technological Characteristics

Materials: ePTFE, FEP, Nitinol, Gold. Self-expanding stent graft. Dimensions: 21-45 mm diameter, 10-20 cm length. Delivery system: 18-24Fr catheter, 0.035" guidewire compatible. Deployment: sewn sleeve with leash lines. Sterilization: not specified. Connectivity: none.

Indications for Use

Indicated for endovascular repair of descending thoracic aorta (DTA) lesions, including isolated lesions and Type B dissections, in patients with adequate iliac/femoral access and appropriate aortic anatomy (16-42 mm diameter). Contraindicated in patients with known material sensitivities or conditions threatening graft infection.

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA

## I. General Information

Device Generic Name: Endovascular Graft

Device Trade Name: GORE® TAG® Thoracic Endoprosthesis

Device Procode: MIH

Applicant's Name and Address: W.L. Gore & Associates, Inc. (Gore)
3450 West Kiltie Lane
Flagstaff, Arizona 86001

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P040043/S051

Date of FDA Notice of Approval: September 10, 2013

Expedited: Not applicable

The GORE® TAG® Thoracic Endoprosthesis original PMA (P040043) was approved on March 23, 2005 for endovascular repair of aneurysms of the descending thoracic aorta (DTA). The indications for use were expanded to include the treatment of isolated lesion (excluding dissections) of the DTA in patients who have appropriate anatomy via P040043/S40 on January 13, 2012, based on the submission of data for the treatment of traumatic transections. The Summaries of Safety and Effectiveness Data (SSED) to support the original approval and the expanded indication are available on the CDRH website and are incorporated by reference here. The current supplement was submitted to further expand the indication for the GORE® TAG® Thoracic Endoprosthesis to include the treatment of all lesions of the DTA, including Type B dissections.

The data presented in this PMA supplement were for use of a modified device design, referred to as the conformable GORE® TAG® Thoracic Endoprosthesis (CTAG Device), as compared to the original PMA device; however, data from studies of this modified device were used to support approval of P040043/S39 and S40, for the treatment of aneurysms of the DTA and isolated lesions of the DTA (excluding dissections), respectively. Therefore, the modified device is currently marketed and this supplement was submitted to expand the indications for the device. The distinction is made because the conformable GORE® TAG® Thoracic Endoprosthesis is referred to as the CTAG Device throughout this

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document in order to distinguish this new device design from previous iterations of the device.

When necessary, previous design iterations are referred to as the TAG Device for clarity. All versions of the device continue to be marketed as the GORE® TAG® Thoracic Endoprosthesis under PMA P040043.

It is important to point out that all previously submitted clinical data were considered with the acute complicated Type B aortic dissection data presented in S51 to support the indication for the CTAG Device to include treatment of all lesions of the DTA.

## II. Indications for Use

The GORE® TAG® Thoracic Endoprosthesis is intended for endovascular repair of all lesions of the descending thoracic aorta, including:

- Isolated lesions in patients who have appropriate anatomy, including:
- Adequate iliac / femoral access
- Aortic inner diameter in the range of 16-42 mm
- ≥ 20 mm non-aneurysmal aorta proximal and distal to the lesion
- Type B dissections in patients who have appropriate anatomy, including:
- Adequate iliac / femoral access
- ≥ 20 mm landing zone proximal to the primary entry tear; proximal extent of the landing zone must not be dissected
- Diameter at proximal extent of proximal landing zone in the range of 16-42 mm

### III. Contraindications

The GORE® TAG® Thoracic Endoprosthesis is contraindicated in:

- Patients with known sensitivities or allergies to the device materials (see Table 1)
- Patients who have a condition that threatens to infect the graft

### IV. Warnings and Precautions

See Warnings and Precautions in the labeling (Instructions for Use).

The following information in this section is important in understanding the anatomical limitations described in the Indications for Use for the treatment of dissections:

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When treating Type B dissections, the proximal extent of the intended proximal landing zone must not be dissected. For example, if the dissection or any hematoma in the proximal extent of the dissection extends up to the LSA, then coverage of the LSA would ensure the proximal end of the device lands in non-dissected tissue. Landing the proximal end of the device in dissected tissue could increase the risk of damage to the septum and could lead to new septal tears, aortic rupture, retrograde dissection, or other complications.

This clarification is needed because of the differences between neck limitations for aneurysms and landing zone limitations for dissections. Healthy neck lengths with the specified characteristics are needed in the treatment of aneurysms, but the landing zones do not need to be completely free of dissection. Additionally, the specific length of non-dissected aorta needed to avoid complications has not been demonstrated.

# V. Device Description

The GORE® TAG® Thoracic Endoprosthesis provides endovascular repair of the DTA. The GORE® TAG® Thoracic Endoprosthesis may be used as a single device or in multiple device combination to accommodate the intended treatment site.

This device is a flexible, self expanding endoprosthesis that is constrained on the leading end of a delivery catheter. The device consists of the two parts, the endoprosthesis and the delivery system (Figures 1 and 2). Endoprosthesis sizes range in diameter 21 to 45mm and in length from 10 to 20cm. The compressed profile of these devices on a delivery catheter ranges from 18 to 24Fr.

The endoprosthesis consists of an ePTFE/FEP graft supported over its entire length by a nitinol wire frame (stent). A radiopaque gold band is embedded in the graft material at each end for device imaging. The stent is attached to the external surface of the graft by laminated ePTFE/FEP bonding tape. The proximal end of the endoprosthesis (stent graft) consists of exposed stent apices called partially uncovered stents, while the distal end of the stent is in line with the graft material. An ePTFE sealing cuff is attached over the stent to each end. For delivery, the endoprosthesis is mounted onto the delivery system. Table 1 lists the materials in the GORE® TAG® Thoracic Endoprosthesis.

Table 1. GORE TAG Thoracic Endoprosthesis Materials

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| Materials |
| --- |
| ePTFE (polytetrafluoroethylene) |
| FEP (fluoroethylpropylene) |
| Nitinol (Nickel, Titanium) |
| Gold |

The delivery system consists of a catheter and a sewn deployment sleeve. The catheter is compatible with a 0.035' guidewire. Leading and trailing olives longitudinally restrain and protect the endoprosthesis during introduction. The leading olive contains a radiopaque marker band and a radiopaque soft tip to facilitate device placement. The trailing olive is constructed using a radiopaque material to facilitate device placement. The endoprosthesis is constrained by the sewn deployment sleeve and is mounted on the leading end of the catheter. Two leash lines attached to the olives and looped through the deployment line on either end of the constrained device prevent the device from rotating on the catheter. Pulling the deployment knob, which is attached to the deployment line system (not shown in **Figure 2**), unlaces the sleeve from the center out and allows the self expanding endoprosthesis to deploy. The sleeve is secured to the stent graft and remains implanted between the endoprosthesis and the vessel wall.


**Figure 1. Conformable GORE® TAG® Thoracic Endoprosthesis**

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Leading End

Trailing End


Figure 2. Delivery System

## VI. Alternative Practices and Procedures

There are several other alternatives for treatment of the descending thoracic aorta including endovascular repair using another endovascular grafting system, surgical implantation of a synthetic graft within the aortic vessel, and medical management. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

## VII. Marketing History

Outside the United States, the GORE TAG Device has been marketed for nearly fifteen years for use in the endovascular repair of the descending thoracic aorta. The Conformable GORE TAG Device (CTAG Device) design iteration has been commercially distributed outside the US since 2009.

Besides the U.S., the CTAG Device is available in the following regions / countries: European Union, Canada, Australia, New Zealand, the Middle East, and Brazil.

The CTAG Device has not been withdrawn from the market for any reason.

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### VIII. Potential Adverse Effects of the Device on Health

Complications associated with the use of the CTAG Device may include, but are not limited to:

- Access, delivery and deployment events (e.g., access failure; deployment difficulties/failures; failure to deliver the stent graft; and insertion or removal difficulty)
- Adynamic ileus
- Allergic reaction (e.g., to contrast, anti-platelet therapy, stent graft material)
- Amputation
- Anesthetic complications
- Aortic expansion (e.g., aneurysm, false lumen, landing zone, lesion)
- Aortic rupture
- Angina
- Atelectasis/pneumonia
- Bleeding (procedural and post-treatment)
- Bowel (e.g., ileus, transient ischemia, infarction, necrosis)
- Branch vessel occlusion or obstruction
- Cardiac (e.g., arrhythmia, myocardial infarction, congestive heart failure, hypotension or hypertension)
- Catheter breakage
- Change in mental status
- Coagulopathy
- Contrast toxicity
- Death
- Dissection, perforation, or rupture of the aortic vessel & surrounding vasculature
- Edema (e.g., leg)
- Embolism (micro and macro) with transient or permanent ischemia
- Endoleak
- Endoprosthesis: improper placement; incomplete deployment; migration; material failure; occlusion; infection; stent fracture; dilatation; perigraft flow
- Erectile dysfunction
- Erosion
- Excessive or inappropriate radiation exposure
- Femoral neuropathy
- Fever and localized inflammation
- Fistula (e.g., aortoeneteric, arteriovenous, aortoesophageal, aortobronchial)
- Genitourinary (e.g., ischemia, erosion, fistula, incontinence, hematuria, infection)
- Hematoma
- Infarction
- Infection (e.g., aneurysm, device or access sites)
- Lymphocele/lymph fistula
- Myocardial infarction
- Neurological damage, local or systemic (e.g., stroke, paraplegia, paraparesis)
- Nerve injury
- Peripheral malperfusion or ischemia
- Persistent false lumen flow
- Post-implant syndrome
- Prosthesis dilatation/rupture
- Prosthetic thrombosis
- Pseudoaneurysm
- Pulmonary complications (e.g., pneumonia, respiratory failure)
- Pulmonary embolism
- Renal (e.g., artery occlusion, contrast toxicity, insufficiency, failure)
- Reoperation
- Restenosis
- Surgical conversion
- Thrombosis
- Transient ischemic attack
- Vascular spasm or vascular trauma (e.g., ilio-femoral vessel dissection, bleeding, rupture)
- Wound (e.g., infection, dehiscence)

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## **IX. Summary of Preclinical Studies**

The SSED containing the preclinical studies to support the indication for the previous TAG Device design is available on the CDRH website and is incorporated by reference here. Approval of the CTAG Device for the treatment of aneurysms included review of new preclinical studies. These data were reviewed under S39 and found adequate to support the broader indication of the treatment of isolated lesions under S40 and Type B dissection of the DTA under S51.

## **X. Summary of Primary Clinical Study**

One primary clinical study (TAG 08-01) and one additional study (TAG 04-01) were conducted to support the expanded indication of all lesions of the DTA for the CTAG Device. Key characteristics of the clinical studies are provided in **Table 2**.

It should be noted that the safety of the CTAG Device for the treatment of all lesions of the DTA was not based on the TAG 08-01 (dissection) and TAG 04-01 (complex pathology including dissection) clinical studies alone, but rather on all the available data for the TAG and CTAG Devices to date, including data from TAG 08-03 (aneurysm) and TAG 08-02 (transection) that was reviewed under previous PMA supplements for the CTAG Device (P040043/S39 and P040043/S40, respectively). Further discussion of the supplementary information considered along with relevant factors regarding the patient populations covered under the indication of all lesions of the DTA will be provided subsequently along with clinical background information on Type B dissections.

**Table 2. Clinical Studies**

| Clinical Study | Study Design | Objective | Number of Sites | Number of Subjects |
| --- | --- | --- | --- | --- |
| TAG 08-01 (Acute Complicated Type B Dissection Pivotal Study) | Prospective, non-randomized, multi-center, single arm | Determine the safety and effectiveness of the CTAG Device for treatment of subjects with acute complicated Type B aortic dissection | Maximum of 50 sites approved for participation. A total of 26 sites enrolled subjects in the study cohort. | 50 enrolled subjects 50 subjects included in primary endpoint analysis. |
| TAG 04-01 (DTA Complex Aortic Pathologies Feasibility Study) | Prospective, non-randomized, multi-center | Assess the initial feasibility of treating complex aortic pathologies with the TAG Device | 14 sites | 59 total (19 acute Type B dissection subjects) |

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# **TAG 08-01 – Acute Complicated Type B Aortic Dissection Pivotal Study Design**

# **A. Study Design**

The TAG 08-01 study (G090009) was a prospective, non-randomized, multi-center, single-arm evaluation, with the primary objective to assess the safety and effectiveness of the CTAG Device in subjects with acute complicated Type B aortic dissection. The primary safety endpoint was all cause mortality incidence through 30 days post-treatment. The primary effectiveness endpoint was exclusion of the primary entry tear at the 1 month follow-up visit (0 to 59 days post-treatment) as assessed by Core Lab analysis, and analyzed using descriptive statistics.

The primary hypothesis of the study was that all-cause mortality incidence through 30 days post-treatment met the performance goal of 25%. The study used Bayesian adaptive design methodology which allowed sample size to vary based on observed outcomes. A maximum of 50 investigative sites and up to 200 subjects were planned for participation in this study with a limit of 15 enrolled subjects per site. Patients were treated between 31 January 2010 and 10 January 2012. The database for this PMA/PMA supplement reflected data collected through 01 February 2013 and included 50 patients. There were 26 investigational sites.

Fifty (50) subjects treated with the CTAG Device for acute complicated Type B dissection were enrolled prior to the initial analysis. Data were to be analyzed after the initial cohort of 50 subjects completed 30 days of follow-up and, if needed, after each subsequent cohort of 25 subjects completed 30 days of follow-up. The three possible outcomes of each planned analysis were:

1) Termination of enrollment for success if the posterior probability using observed data was sufficient to meet the performance goal (99% probability or greater for 50 and 75 subject interim checks, 97.5% thereafter).
2) Continued accrual due to a reasonable predictive probability (10% or greater) that the performance goal could be met with the enrollment of additional subjects.
3) Termination of enrollment for futility if the predictive probability that the performance goal could be met with the enrollment of additional subjects was less than 10%.

**Table 3** summarizes the sample size simulations and the probability required for determining study success at each analysis.

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**Table 3. Probability Required for Determining Study Success at Each Analysis**

| Analysis | Posterior Probability = Pr (θ < 0.25 | data) | Decision | Posterior Predictive Probability of Study Success = Pr (success | data) | Decision |
| --- | --- | --- | --- | --- | --- | --- |
| N=50 | ≥ 0.99 | Stop (effective) | <0.10 | Stop (futility) |
| N=75 | ≥ 0.99 | Stop (effective) | <0.10 | Stop (futility) |
| N=100 | ≥ 0.975 | Stop (effective) | <0.10 | Stop (futility) |
| N=125 | ≥ 0.975 | Stop (effective) | <0.10 | Stop (futility) |
| N=150 | ≥ 0.975 | Stop (effective) | <0.10 | Stop (futility) |
| N=175 | ≥ 0.975 | Stop (effective) | <0.10 | Stop (futility) |
| N=200 | ≥ 0.975 | Meet Performance Goal | | |

Simulations of 100,000 clinical trials were conducted versus a range of values for the CTAG Device versus the performance goal value (0.25). The analysis strategy described controls the frequentist Type I error at 4.98% at the performance goal value of 0.25. These simulations took into account the potential premature termination of the study due to futility based on the predictive probability calculation at each point. These simulated calculations were made using exact results, since all of the distributions involved are solvable in closed form. A summary of the frequentist power calculation is provided in **Table 4**.

**Table 4. Simulated Power under Planned Analysis Scenario vs Performance Goal**

| | | 0.25 (Performance Goal) |
| --- | --- | --- |
| CTAG Device 30 Day Mortality | 0.1 | 100 |
| | 0.11 | 100 |
| | 0.12 | 99 |
| | 0.13 | 98 |
| | 0.14 | 96 |
| | 0.15 | 92 |
| | 0.16 | 85 |
| | 0.17 | 76 |
| | 0.18 | 65 |
| | 0.19 | 53 |
| | 0.2 | 41 |

Note: Entries represent percent of simulated trials which concluded that the CTAG Device cohort meets the performance goal (0.25) given the proportions listed.

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Three separate external evaluation groups independently reviewed data for this study. They included a Data and Safety Monitoring Board (DSMB), a Clinical Events Committee (CEC), and an independent imaging Core Lab.

The DSMB was utilized to review all study data. After review of study data, the DSMB made recommendations to the sponsor. Recommendations could have included modifying the study, stopping the study, or continuing the study without modification. The DSMB made no recommendations to modify or discontinue the TAG 08-01 study.

The CEC was utilized to review adverse event data to ensure consistent and accurate AE and death reporting and classification. All major adverse events and major device events were adjudicated for accurate reporting of the adverse event severity, relationship to aortic rupture or malperfusion and relationship to the device or endovascular procedure through 1 year post-procedure. Each event was independently reviewed by three CEC members or by full panel review in cases of disagreement. A subcommittee of the CEC, comprised of two neurologists, was formed during the conduct of the study to evaluate several factors associated with the general event of stroke.

The imaging Core Lab, AortaCore, located at the University of Wisconsin-Madison was utilized to provide a separate review of CT and radiograph films collected for the study. In addition, the primary effectiveness endpoint result was based on the Core Lab assessment.

### 1. Clinical Inclusion and Exclusion Criteria

Subjects were screened and eligibility for enrollment into the study was determined by the Investigator. Pre-treatment evaluation included a contrast enhanced spiral computed tomographic angiography (CTA) of the chest, abdomen, and pelvis to assess aortic morphology and vascular characteristics. A physical exam including assessment for inclusion/exclusion criteria, medical history, subject risk status using Society of Vascular Surgery (SVS) and the American Society of Anesthesiology (ASA) guidelines, blood pressure, concomitant medications and serum creatinine concentration was performed for each subject.

Enrollment in the study was limited to patients who met the following inclusion criteria:

1) Presence of acute complicated Type B aortic dissection:

- Dissection is acute
Time from symptom onset to dissection diagnosis ≤14 days
- Dissection is complicated
Subject must present with at least one of the following:

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- Rupture in the setting of an aortic dissection defined as hemorrhage outside of the aortic boundaries which is noted by CT scan (hemorrhage must be differentiated from reactive effusions by the investigator, or if equivocal, having elevated Hounsefield units as determined by the radiologist)
- Clinical evidence of malperfusion, in the setting of an aortic dissection, defined as:
- Clinical or radiographic evidence of visceral hypoperfusion
- Clinical or radiographic evidence of renal hypoperfusion
- Clinical or radiographic evidence of lower extremity hypoperfusion
- Clinical or radiographic evidence of spinal cord hypoperfusion
- Dissection is Type B
Entire dissection is distal to the left subclavian artery
- Primary Treatment Indication is Class 1 Aortic Dissection
Classical aortic dissection with intimal flap between true and false lumen with double barrel flow in thoracic aorta
- Subjects with multiple entry tears are allowed to be enrolled in the study
2) Age 18 to 80 years
3) Primary treatment is endovascular treatment with the CTAG Device.
Adjunctive treatments may include left subclavian artery revascularization, percutaneous fenestration, aortic stenting, peripheral vessel stenting, surgical fenestration, and/or peripheral artery bypass
4) Proximal landing zone characteristics include:
- Proximal extent of intended proximal landing zone cannot be dissected
- Length ≥ 2.0 cm proximal to the primary entry tear
- Trans-aortic diameter at proximal extent of intended landing zone between 16-42 mm (diameter assessed by flow lumen and thrombus, if present; calcium excluded)
- Cannot be aneurysmal, heavily calcified, or have excessive intraluminal thrombus
- Must be native aorta
- May include left subclavian artery, if necessary
5) Subject is capable of complying with protocol requirements, including follow-up
6) Informed Consent Form is signed by subject or legal representative

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Patients were not permitted to enroll in the study if they met any of the following exclusion criteria:

1) Primary treatment indication is Class 2-5 aortic dissection (intramural hematoma, limited dissection, penetrating atherosclerotic ulcer, iatrogenic dissection, traumatic dissection)
2) Concomitant aneurysm/disease of the ascending aorta, aortic arch, or abdominal aorta requiring repair (dissection extension into the abdominal aorta is acceptable)
3) Prior repair of DTA
4) Infected aorta
5) Subject has a systemic infection and may be at increased risk of endovascular graft infection
6) Persistent refractory shock (systolic blood pressure <90 mm Hg)
7) Bowel necrosis (bowel necrosis characterized by direct observation with surgical exploration, or elevated serum lactate level and CT findings of portal venous gas, free intra-abdominal gas, pneumatosis intramural gas, and poor mucosal enhancement of thickened bowel wall)
8) Renal failure, defined as baseline creatinine ≥ 2.5 mg/dl
9) ASA risk classification = V (moribund patient not expected to live 24 hours with or without operation)
10) Pregnant female
11) Major surgery within 30 days of treatment (other than left subclavian artery bypass or transposition)
12) Degenerative connective tissue disease (e.g., Marfan or Ehler-Danlos Syndrome)
13) Treatment in another drug or medical device study within 1 year of study enrollment
14) History of stimulant abuse (e.g., cocaine or amphetamine) within 1 year of treatment
15) Tortuous or stenotic iliac and/or femoral arteries and the inability to use a conduit for vascular access
16) Planned coverage of left carotid or celiac arteries with the CTAG Device
17) The planned endovascular procedure involves alterations to the CTAG Device
18) Subject has known sensitivities or allergies to the device materials

## 2. Follow-up Schedule

Preoperatively, subjects were required to have a spiral CT, physical examination, and serum creatinine concentration measurement to assess their eligibility for participation in the study.

The subject schedule of follow-up is described in Table 5. This included returning for follow-up visits at 1 month, 6 months, 1 year and annually thereafter

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through 5 years. Follow-up procedures required a physical examination, four view chest X-ray, spiral CT of the chest, abdomen, and pelvis (contrast and non-contrast), and assessment for adverse events and device events.

**Table 6** provides a description of the pre-operative and post-operative evaluations and assessments that were performed to assess subject eligibility and effectiveness endpoints. Adverse events and complications were recorded at all visits.

**Table 5. TAG 08-01 Subject Schedule of Events**

| Diagnostic Test | Pre-treatment | Treatment | Discharge | 1 month | 6 months | Annually for up to 5 years |
| --- | --- | --- | --- | --- | --- | --- |
| Physical examination | X | | X | X | X | X |
| Creatinine Concentration | X | | | | | |
| Spiral CT | X | | X | X | X | X |
| Angiogram | | X | | | | |
| Chest x-ray | | | X | X | X | X |

**Table 6. Description of Pre-Operative & Post-Operative Evaluations & Assessments**

| Timepoint | Evaluative point | Description | Evaluative Tools | Assessment Point |
| --- | --- | --- | --- | --- |
| Pre-Operative | Anatomic Eligibility | Patient Eligibility | CT Scan with/without contrast | Candidacy for endovascular repair |
| | Medical Eligibility | Patient Eligibility | Physical Exam | Verify study inclusion/exclusion criteria including the presence of an acute, complicated dissection |
| | Renal Function | Patient Eligibility | Serum Creatinine | Verify study inclusion/exclusion criteria and potential for contrast-enhanced follow-up evaluations |
| Post-Operative | Vital Status | Primary Safety Endpoint (Evaluated at 30 Days) | Any | Verify that the subject was alive at 30 days post-procedure |
| | Primary Entry Tear Exclusion | Primary Effectiveness Endpoint (Evaluated at 1 Month) | Contrast-enhanced CT scan | False lumen is not perfused through the primary entry tear as visualized by contrast dye. Core Lab evaluated. |
| | False Lumen Thrombosis | Secondary Effectiveness Endpoint (Evaluated at each follow-up visit) | Contrast-enhanced CT scan | Characterization of false lumen status adjacent and distal to the stent graft. Core Lab evaluated. |

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| Timepoint | Evaluative point | Description | Evaluative Tools | Assessment Point |
| --- | --- | --- | --- | --- |
| | Dissection-Based Interventions | Secondary Effectiveness Endpoint (Evaluated at each follow-up visit) | Contrast-enhanced CT scan, Physical Exam | Identification of surgical/endovascular procedures performed and associated with underlying disease process (malperfusion or rupture). Events occurring within one year of procedure are adjudicated by CEC. |
| | Aortic Rupture | Secondary Effectiveness Endpoint (Evaluated at each follow-up visit) | Contrast-enhanced CT scan, Physical Exam, Autopsy | Freedom from aortic rupture. |

### 3. Clinical Endpoints

With regards to safety, the primary hypothesis of the study was that all-cause mortality incidence through 30 days post-treatment met the performance goal of 25%. The performance goal was justified based on historical data, including the SVS Master File¹, open and endovascular literature, and the International Registry of Acute Aortic Dissection (IRAD) data available at the time the protocol was developed.

With regards to effectiveness, the primary effectiveness endpoint of primary entry tear exclusion was evaluated for subjects completing a 1 month visit with CT or MR imaging provided to the Core Lab.

Secondary effectiveness endpoints were evaluated at 1 month, 6 months and 12 months, and included the following:

- False Lumen Thrombosis (evaluated by Core Lab analysis). This was evaluated at each follow-up visit and categorized as follows:
- Incomplete thrombosis – presence of blood flow in any portion of the false lumen parallel to the stent graft, excluding the distal 2cm.
- Complete thrombosis – absence of blood flow in any portion of the false lumen parallel to the stent graft, excluding the distal 2cm.
- No false lumen thrombosis - presence of blood flow throughout the entire false lumen within the descending thoracic aorta parallel to the stent graft.
- Additional Dissection Based Intervention Rate (reported by site) defined as interventions that were related to malperfusion or aortic rupture.
- Aortic Rupture (reported by the site).

Although the primary and secondary effectiveness endpoints were not hypothesis driven, they are clinically meaningful in assessing the effectiveness of treatment of acute complicated Type B dissections. These effectiveness endpoints were qualitatively compared to historical endovascular literature and were found to be comparable.

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With regard to success/failure criteria, the overall TAG 08-01 study was considered successful if the primary safety endpoint result met the pre-specified performance goal. No individual subject success/failure criteria were defined in the protocol.

## B. Accountability of PMA Cohort

Subjects were screened and enrolled per the procedures per the protocol. A total of 170 patients were screened for eligibility in the TAG 08-01 study; 120 subjects were excluded from study participation (Figure 3). The reasons for screen failure included:

- Anatomic considerations due to proximal landing zone characteristics per inclusion criterion 4 or inadequate access per exclusion criterion 15 (n=28)
- Subject not presenting with an acute complicated Type B dissection as defined in the protocol per inclusion criterion 1 or exclusion criterion 1 (n=47)
- Concomitant disease/disease process per exclusion criteria 2-8 or 12 (n=22)
- Primary treatment plan was not placement of a thoracic stent graft per inclusion criterion 3 or exclusion criteria 16-17 (n=12)
- Age requirements per inclusion criterion 2 (n=2)
- Drug abuse/study compliance per inclusion criterion 5 or exclusion criterion 14 (n=5)
- Major surgery within 30 days per exclusion criterion 11 (n=2)
- Inability to obtain informed consent per inclusion criterion 6 (n=2)

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**Figure 3. TAG 08-01 Study Subject Disposition Flowchart**

A total of 50 subjects were enrolled at 26 investigative sites from January 2010 to January 2012. All enrolled subjects underwent endovascular repair with the CTAG Device to treat acute complicated Type B aortic dissection. Subjects enrolled in TAG 08-01 were required to return for follow-up visits as described in **Table 5**.

**Table 7** summarizes compliance with protocol required visits and imaging along with discontinuation from the study. All subject visits through 12 months are complete. Subjects remain in follow-up therefore data beyond 12 months are incomplete.

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**Table 7. Subject Disposition and Compliance by Study Interval**

| Study Period | Eligible for follow-up | Follow-up Compliance | | | Events Prior to Next Interval | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Subjects with Visit in Window | CT Scan performed^{1} | X-Ray performed^{1} | Death^{1} | Discontinued^{1} | Not Due for Next F/U^{1} |
| Procedure | 50 | - | - | - | 2 (4.0%) | 0 (0.0%) | 0 (0.0%) |
| Post-Procedure | 48 | - | - | - | 2 (4.2%) | 1 (2.1%) | 0 (0.0%) |
| 1 Month | 45 | 45 (100.0%) | 41 (91.1%) | 39 (86.7%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| 6 Months | 45 | 41 (91.1%) | 38 (84.4%) | 34 (75.6%) | 2 (4.4%) | 0 (0.0%) | 0 (0.0%) |
| 12 Months | 43 | 39 (90.7%) | 38 (88.4%) | 35 (81.4%) | 0 (0.0%) | 2 (4.7%) | 8 (18.6%) |
| 24 Months | 33 | 20 (60.6%) | 20 (60.6%) | 16 (48.5%) | 0 (0.0%) | 1 (3.0%) | 23 (69.7%) |
| 36 Months | 9 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 9 (100.0%) |
| 48 Months | 0 | - | - | - | - | - | - |
| 60 Months | 0 | - | - | - | - | - | - |

Study period definitions: Procedure(0-6 days) Post-Procedure(1-14 days) 1 Month(15-59 days) 6 Months(60-242 days) 12 Months(243-546 days) 24 Months(547-911 days) 36 Months(912-1275 days) 48 Months(1276-1640 days) 60 Months(1641-2006 days)

$^{1}$ Percentages are based on number of subjects in visit window. Compliance is based on site reported imaging assessments.

### **C. Study Population Demographics and Baseline Parameters**

Baseline assessments of TAG 08-01 study subjects include demographics, presenting dissection characteristics, risk factor evaluations, medical history, and radiological aortic assessment.

**Table 8** provides a summary of demographic data. A majority of subjects (74%) were male. Caucasians comprised 56.0% of the cohort. Median subject age was 57.5 years (range: 31-83 years).

Subject medical history is presented in **Table 9**. Most commonly noted at the pre-treatment visit were hypertension, history of smoking, and hypercholesterolemia.

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**Table 8. Subject Demographics**

| | TAG 08-01 Cohort |
| --- | --- |
| **Number of Enrolled Subjects** | 50 |
| **Gender** | |
| Male | 37 (74.0%) |
| Female | 13 (26.0%) |
| **Ethnicity** | |
| Not Hispanic or Latino | 46 (92.0%) |
| Hispanic or Latino | 4 (8.0%) |
| **Race** | |
| White or Caucasian | 28 (56.0%) |
| Black or African American | 17 (34.0%) |
| Asian / Oriental | 1 (2.0%) |
| American Indian or Alaskan Native | 1 (2.0%) |
| Native Hawaiian or Other Pacific Islander | 0 (0.0%) |
| Middle Eastern | 0 (0.0%) |
| Other | 3 (6.0%) |
| Unknown | 0 (0.0%) |
| **Age (yrs)** | |
| n | 50 |
| Mean (Std Dev) | 57.1 (11.6) |
| Median | 57.5 |
| Range | (31.0, 83.0) |
| **Weight (kg)** | |
| n | 50 |
| Mean (Std Dev) | 97.4 (23.5) |
| Median | 94.3 |
| Range | (58.5, 148.0) |
| **Height (cm)** | |
| n | 49 |
| Mean (Std Dev) | 173.5 (10.2) |
| Median | 175.0 |
| Range | (152.4, 201.0) |

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**Table 9. Subject Medical History**

| | TAG 08-01 Cohort |
| --- | --- |
| Number of Enrolled Subjects | 50 |
| Hypertension | 47 (94.0%) |
| Cigarette Smoking | 27 (54.0%) |
| Hypercholesterolemia | 16 (32.0%) |
| Renal Insufficiency | 11 (22.0%) |
| COPD | 10 (20.0%) |
| Cardiac Arrhythmia | 10 (20.0%) |
| Diabetes Mellitus | 9 (18.0%) |
| CAD | 7 (14.0%) |
| Myocardial Infarction | 6 (12.0%) |
| Cancer | 5 (10.0%) |
| Peripheral Vascular Disease | 5 (10.0%) |
| Stroke | 5 (10.0%) |
| CHF | 3 (6.0%) |
| CABG | 2 (4.0%) |
| Cardiac Surgery | 2 (4.0%) |
| Carotid Disease | 2 (4.0%) |
| Prior Aortic Dissection | 2 (4.0%) |
| Abdominal Aortic Aneurysm | 1 (2.0%) |
| Paraplegia | 1 (2.0%) |
| TIA | 1 (2.0%) |
| Abdominal Aortic Surgery | 0 (0.0%) |
| Aortic Valve Replacement | 0 (0.0%) |
| Thoracotomy | 0 (0.0%) |

Since the Society for Vascular Surgery Master File (SVS MF) was used in developing the performance goal, the baseline characteristics (demographics and medical history) were compared to investigate potential differences between the datasets as shown in **Table 10**. Although some differences were noted in the comparison of the SVS MF and the TAG 08-01 study patient population such as smoking status, renal malperfusion, lower extremity malperfusion and ASA classification, the majority of the baseline characteristics were comparable between the two datasets. Therefore, the overall patient population from this PMA study is comparable to the patient population from the SVS MF and the use of the SVS MF in evaluating study results is reasonable.

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Table 10. Baseline Characteristics Comparison

| Variable | Level | TAG 08-01 n=50 | SVS Master File n=85 | p-value^{1} |
| --- | --- | --- | --- | --- |
| *Demographics* N (%) unless otherwise indicated | | | | |
| Gender | Male | 37 (74.0) | 62 (72.9) | 1.00 |
| | Female | 13 (26.0) | 23 (27.1) | |
| Age in years, mean (sd) | | 57.1 (11.6) | 58.8 (15.4) | 0.51 |
| Race | White/Caucasian | 28 (56.0) | 45 (52.9) | 0.94 |
| | Black/African American | 17 (34.0) | 23 (27.1) | |
| | American Indian/Alaskan Native | 1 (2.0) | 1 (1.2) | |
| | Native Hawaiian/Pacific Islander | 0 (0.0) | 1 (1.2) | |
| | Asian | 1 (2.0) | 3 (3.5) | |
| Hispanic Ethnicity | Hispanic | 4 (8.0) | 12 (14.1) | 0.41 |
| | Non-Hispanic | 46 (92.0) | 72 (84.7) | |
| *Medical History* | | | | |
| Diabetes | Yes | 9 (18.0) | 11 (12.9) | 0.46 |
| Cancer | Yes | 5 (10.0) | 8 (9.4) | 1.00 |
| Cerebrovascular Event | Yes | 5 (10.0) | 3 (3.5) | 0.15 |
| TIA | Yes | 1 (2.0) | 0 (0.0) | 0.37 |
| COPD | Yes | 10 (20.0) | 9 (10.6) | 0.20 |
| CHF | Yes | 3 (6.0) | 9 (10.6) | 0.53 |
| HTN | Yes | 47 (94.0) | 71 (83.5) | 0.11 |
| MI | Yes | 6 (12.0) | 10 (11.8) | 1.00 |
| Arrhythmia | Yes | 10 (20.0) | 10 (11.8) | 0.22 |
| Smoking Status^{2} | Current | 25 (50.0) | 27 (31.8) | <0.0001 |
| | Prior History | 2 (4.0) | 31 (36.5) | |
| | Never Smoked | 23 (46.0) | 25 (29.4) | |
| *Diagnosis* | | | | |
| Rupture | Yes | 11 (22.0) | 27 (31.8) | 0.24 |
| Malperfusion | Yes | 41 (82.0) | 61 (71.8) | 0.22 |
| Visceral Malperfusion | Yes | 15 (30.0) | 12 (14.1) | 0.26 |
| Renal Malperfusion | Yes | 30 (60.0) | 22 (25.9) | 0.012 |
| Lower Extremity Malperfusion | Yes | 18 (36.0) | 34 (40.0) | 0.056* |
| Spinal Malperfusion | Yes | 3 (6.0) | 2 (2.4) | 0.66 |
| ASA Grade | 1 | 2 (4.0) | 0 (0.0) | 0.0038 |
| | 2 | 2 (4.0) | 2 (2.4) | |
| | 3 | 20 (40.0) | 19 (22.4) | |
| | 4 | 26 (52.0) | 55 (64.7) | |
| | 5 | 0 (0.0) | 9 (10.6) | |

$^{1}$ p-values are based on Fisher's exact test for categorical variables and two-sample t-tests for continuous variables.

$^{2}$ TAG 08-01 smoking categories were condensed to match with closest SVS MF category.

*In SVS group there were 24 missing values for lower extremity malperfusion, for a rate of 55.7% among the nonmissing, which is reflected in the p-value.

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Table 11 summarizes pre-treatment risk using several criteria including ASA and New York Heart Association (NYHA) Functional Classification. Most subjects were classified as ASA IV, defined as severe systemic disease that is a constant threat to life. Few subjects were enrolled with notable cardiac dysfunction based on the NYHA classification.

Table 12 summarizes details of the presentation of the aortic dissection, including symptoms, days from symptom onset to diagnosis, complications of dissection and malperfused vascular beds in the subset of subjects enrolled with malperfusion syndrome. Back, chest, and abdominal pain were the most commonly reported symptoms. All subjects were diagnosed with aortic dissection within 14 days of symptom onset. Thirty nine (39) subjects presented with malperfusion (78%), 9 with rupture (18%) and 2 with both malperfusion and rupture. Subjects presenting with malperfusion may have more than one vascular bed/organ malperfused. Renal malperfusion was present in 30 subjects (73%), followed by lower limb malperfusion in 18 (44%) and visceral malperfusion in 15 (37%). Spinal cord malperfusion was seen in 3 subjects (7%). The majority of dissections extended down to the iliac arteries (60%). Table 13 summarizes the observed malperfusion combinations.

Subjects underwent pre-treatment imaging to assess aortic morphology and whether appropriate anatomy existed for inclusion in the TAG 08-01 study (Table 14). Criteria for enrollment included proximal landing zone length ≥ 2.0 cm from the primary entry tear to the left common carotid and proximal aortic diameter measured within the range of 16-42 mm.

Table 11. Pre-Treatment Risk Summary

| | TAG 08-01 Cohort |
| --- | --- |
| Number of Enrolled Subjects | 50 |
| ASA Classification | |
| I | 2 (4.0%) |
| II | 2 (4.0%) |
| III | 20 (40.0%) |
| IV | 26 (52.0%) |
| V | 0 (0.0%) |
| NYHA Classification | |
| I | 11 (22.0%) |
| II | 6 (12.0%) |
| III | 1 (2.0%) |
| IV | 0 (0.0%) |
| No Cardiac Disease | 32 (64.0%) |

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**Table 12. Presenting Dissection Characteristics**

| | TAG 08-01 Cohort |
| --- | --- |
| **Number of Enrolled Subjects** | 50 |
| **Symptoms of Aortic Dissection** | |
| Back Pain | 40 (80.0%) |
| Chest Pain | 33 (66.0%) |
| Abdominal Pain | 25 (50.0%) |
| Peripheral Pulse Deficit | 15 (30.0%) |
| Leg Pain | 7 (14.0%) |
| Hypotension | 3 (6.0%) |
| Syncope | 2 (4.0%) |
| Dysphonia | 1 (2.0%) |
| Dysphagia | 0 (0.0%) |
| Hemoptysis | 0 (0.0%) |
| **Days from Symptom Onset to Diagnosis** | |
| n | 50 |
| Mean (Std Dev) | 1.2 (1.8) |
| Median | 0.4 |
| Range | (0.0, 7.3) |
| **Days from Symptom Onset to Diagnosis** | |
| <7 Days | 49 (98.0%) |
| 7-14 Days | 1 (2.0%) |
| >14 Days | 0 (0.0%) |
| **Known Distal Extent of Dissection (Core Lab)** | |
| DTA | 5 (10.0%) |
| Celiac | 4 (8.0%) |
| SMA | 1 (2.0%) |
| Renals | 5 (10.0%) |
| IMA | 5 (10.0%) |
| Iliacs | 30 (60.0%) |
| **Complications of Dissection** | |
| Malperfusion | 39 (78.0%) |
| Rupture | 9 (18.0%) |
| Malperfusion and Rupture | 2 (4.0%) |
| **Subjects with Malperfusion^{1}** | 41 |
| Visceral Malperfusion | 15 (36.6%) |
| Renal Malperfusion | 30 (73.2%) |
| Lower Extremity Malperfusion | 18 (43.9%) |
| Spinal Cord Malperfusion | 3 (7.3%) |

$^{1}$ Percentages below this heading use this value as the denominator.

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**Table 13. Observed Malperfusion Combinations**

| | TAG 08-01 Cohort |
| --- | --- |
| Number of Enrolled Subjects | 50 |
| Subjects with Malperfusion | 41 |
| Presenting Malperfused Vascular Beds | |
| Renal Only | 12(29.3%) |
| Lower Extremity Only | 7(17.1%) |
| Visceral and Renal | 7(17.1%) |
| Renal and Lower Extremity | 5(12.2%) |
| Visceral Only | 3(7.3%) |
| Visceral, Renal, and Lower Extremity | 3(7.3%) |
| Renal and Spinal Cord | 1(2.4%) |
| Renal, Lower Extremity, and Spinal Cord | 1(2.4%) |
| Visceral and Lower Extremity | 1(2.4%) |
| Visceral, Renal, Lower Extremity, and Spinal Cord | 1(2.4%) |
| Lower Extremity and Spinal Cord | 0(0.0%) |
| Spinal Cord Only | 0(0.0%) |
| Visceral and Spinal Cord | 0(0.0%) |
| Visceral, Lower Extremity, and Spinal Cord | 0(0.0%) |
| Visceral, Renal, and Spinal Cord | 0(0.0%) |

**Table 14. Pre-Treatment Imaging Characteristics (Site Reported)**

| | TAG 08-01 Cohort |
| --- | --- |
| Number of Enrolled Subjects | 50 |
| **Aortic Diameter at Proximal Implantation Site (mm)** | |
| n | 49 |
| Mean (Std Dev) | 30.8 (3.8) |
| Median | 31.0 |
| Range | (24.0, 42.0) |
| **Maximum True Lumen Diameter (mm)** | |
| n | 50 |
| Mean (Std Dev) | 24.5 (8.9) |
| Median | 23.5 |
| Range | (8.0, 58.0) |
| **Minimum True Lumen Diameter (mm)** | |
| n | 50 |
| Mean (Std Dev) | 11.6 (8.9) |
| Median | 10.0 |
| Range | (0.0, 46.0) |
| **Maximum False Lumen Diameter (mm)** | |
| n | 50 |
| Mean (Std Dev) | 28.0 (8.5) |
| Median | 28.5 |
| Range | (12.0, 45.0) |
| **Maximum Transverse Diameter (mm)** | |
| n | 50 |

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| | **TAG 08-01 Cohort** |
| --- | --- |
| Mean (Std Dev) | 40.2 (8.1) |
| Median | 38.5 |
| Range | (28.0, 65.0) |
| **Proximal Neck Length (Primary Entry Tear-LCCA) (cm)** | |
| n | 49 |
| Mean (Std Dev) | 4.9 (3.8) |
| Median | 3.5 |
| Range | (2.0, 16.3) |
| **Dissection Length (cm)** | |
| n | 47 |
| Mean (Std Dev) | 35.1 (15.7) |
| Median | 38.3 |
| Range | (3.9, 66.0) |
| **Distal Re-entry Tears** | |
| No | 18 (36.0%) |
| Yes | 31 (62.0%) |
| Missing | 1 (2.0%) |
| **Left Common Iliac Diameter (mm)** | |
| n | 49 |
| Mean (Std Dev) | 14.6 (3.7) |
| Median | 14.0 |
| Range | (7.0, 27.0) |
| **Left External Iliac Diameter (mm)** | |
| n | 49 |
| Mean (Std Dev) | 9.6 (2.1) |
| Median | 10.0 |
| Range | (0.0, 13.0) |
| **Right Common Iliac Diameter (mm)** | |
| n | 49 |
| Mean (Std Dev) | 13.6 (3.4) |
| Median | 14.0 |
| Range | (4.0, 25.0) |
| **Right External Iliac Diameter (mm)** | |
| n | 49 |
| Mean (Std Dev) | 9.9 (2.1) |
| Median | 10.0 |
| Range | (0.0, 15.0) |

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### Treatment Details

A summary of treatment characteristics is provided in **Table 15**. Included are general characteristics on access method and site, anesthesia, and adjunctive techniques to prevent paraplegia. All procedures (100%) were performed under general anesthesia and vascular access was gained via the femoral artery in 92% (cut-down in 74%, percutaneous in 20% and conduit in 6%). Adjunctive techniques to prevent paraplegia were performed (CSF drainage in 64.7% and induced hypertension in 5.9%). The left subclavian artery (LSA) was covered completely in 54% of subjects and partially covered in 18% of subjects. LSA bypass was performed in 14% and transposition in 4%. Proximal device implantation occurred in Zone 2 for 72% of subjects and Zone 3 / 4 for 28%.

Device use data are provided in **Table 16** and **Table 17**. The majority of cases were treated with one device with a significant portion of Investigators also electing to use a second device. The mean device use per subject was 1.5 devices. Generally, longer devices were used with 10cm length devices only accounting for 15% of total devices used. The most common device diameter was 34mm which is roughly in the middle of the CTAG Device diameter portfolio.

Device usage in the study was consistent with the expectations of use to treat aortic dissection. The treatment goal is exclusion of the primary entry which usually can be accomplished with one device. Additional implanted devices can constitute a surgeon's decision to extend the treatment zone to exert more longitudinal pressure on the false lumen, cover a significant fenestration in the aortic septum, or part of a conservative approach in an aortic rupture. The distribution of device diameters may be characteristic of middle-age subjects who are starting to exhibit underlying vascular disease and whose aorta has not gone through a degenerative process as much as the typical aneurysm patient.

The TAG 08-01 study procedural outcomes are displayed in **Table 18**. All subjects survived the endovascular procedure. The median case time was 168 minutes and the median blood loss was 200mL. The median hospital stay after endovascular treatment with the CTAG Device was 10 days (range 0-41 days). All subjects had ICU stay and with a median ICU stay was 4.8 days. The hospital survival was 92% as noted in **Table 23**. Fifty-two percent (52%) of subjects underwent an adjunctive procedure at the index procedure with placement of a peripheral stent being the most common procedure. These adjunctive procedures were intended to address the complications of the aortic dissection itself and the presenting symptoms, rather than related to the placement of the device.

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**Table 15. Summary of Treatment Characteristics**

| | TAG 08-01 Cohort |
| --- | --- |
| **Number of Enrolled Subjects** | 50 |
| **LSA Procedure** | |
| None | 41 (82.0%) |
| Transposed | 2 (4.0%) |
| Bypassed | 7 (14.0%) |
| **Access Method** | |
| Percutaneous | 10 (20.0%) |
| Cut-Down | 37 (74.0%) |
| Cut-Down and Conduit | 3 (6.0%) |
| **Access Site** | |
| Femoral Artery | 46 (92.0%) |
| Iliac Artery | 4 (8.0%) |
| Infrarenal Aorta | 0 (0.0%) |
| **Anesthesia Method** | |
| General | 50 (100.0%) |
| Regional | 0 (0.0%) |
| Local | 0 (0.0%) |
| **Adjunctive Techniques to Prevent Paraplegia^{1}** | 17 (34.0%) |
| CSF Drainage | 11 (64.7%) |
| Induced Hypertension | 1 (5.9%) |
| Other | 5 (29.4%) |
| **Proximal Implantation Zone** | |
| Zone 2 | 36 (72.0%) |
| Zone 3 / Zone 4 | 14 (28.0%) |
| **LSA Coverage** | |
| Complete | 27 (54.0%) |
| Partial | 9 (18.0%) |
| None | 14 (28.0%) |

$^{1}$ This count used as denominator for percentages under this heading.

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**Table 16. Implanted Device Characteristics$^{1}$**

| Proximal Diameter (mm) | Distal Diameter (mm) | Length (cm) | Initial Procedure | |
| --- | --- | --- | --- | --- |
| | | | Subjects^{2} (N=50) n (%) | Devices^{3} (N=74) n (%) |
| 28 | 28 | 10 | 2 (4.0%) | 2 (2.7%) |
| 28 | 28 | 15 | 3 (6.0%) | 3 (4.1%) |
| 31 | 31 | 10 | 2 (4.0%) | 2 (2.7%) |
| 31 | 31 | 15 | 12 (24.0%) | 14 (18.9%) |
| 34 | 34 | 10 | 2 (4.0%) | 2 (2.7%) |
| 34 | 34 | 15 | 6 (12.0%) | 6 (8.1%) |
| 34 | 34 | 20 | 17 (34.0%) | 17 (23.0%) |
| 37 | 37 | 10 | 3 (6.0%) | 3 (4.1%) |
| 37 | 37 | 15 | 6 (12.0%) | 6 (8.1%) |
| 37 | 37 | 20 | 5 (10.0%) | 5 (6.8%) |
| 40 | 40 | 10 | 2 (4.0%) | 2 (2.7%) |
| 40 | 40 | 15 | 6 (12.0%) | 6 (8.1%) |
| 40 | 40 | 20 | 4 (8.0%) | 4 (5.4%) |
| 45 | 45 | 20 | 2 (4.0%) | 2 (2.7%) |

$^{1}$Five GORE TAG Device sizes were not implanted as part of this study. Those sizes are the 21mm x 21mm x 10cm, 26mm x 21mm x 10cm, 26mm x 26mm x 10cm, 31mm x 26mm x 10cm, and 45mm x 45mm x 15cm. The 45mm x 45mm x 10cm was not implanted during an initial procedure, but was implanted during a reintervention.

$^{2}$All percentages based on number of subjects enrolled.

$^{3}$All percentages based on number of devices implanted.

**Table 17. Summary of Number of CTAG Devices per Subject at Initial Procedure**

| | Malperfusion Subgroup | Rupture Subgroup | TAG 08-01 Cohort |
| --- | --- | --- | --- |
| Number of Enrolled Subjects | 39 | 11 | 50 |
| Number of Subjects With Successful Initial Implant | 39 | 11 | 50 |
| Number of Implanted Endoprostheses (Initial Implant) | | | |
| 1 | 25 (64.1%) | 6 (54.5%) | 31 (62.0%) |
| 2 | 12 (30.8%) | 3 (27.3%) | 15 (30.0%) |
| 3 | 2 (5.1%) | 1 (9.1%) | 3 (6.0%) |
| 4 | 0 (0.0%) | 1 (9.1%) | 1 (2.0%) |
| n | 39 | 11 | 50 |
| Mean (Std Dev) | 1.4 (0.6) | 1.7 (1.0) | 1.5 (0.7) |
| Median | 1.0 | 1.0 | 1.0 |
| Range | (1.0, 3.0) | (1.0, 4.0) | (1.0, 4.0) |

**Table 18. Summary of Procedural Outcomes**

| | TAG 08-01 Cohort | 95% CI |
| --- | --- | --- |
| Number of Enrolled Subjects | 50 | |
| Procedure Time (minutes) | | |
| n | 50 | |
| Mean (Std Dev) | 175.3 (99.9) | (147.6, 203.0) |
| Median | 168.0 | |
| Range | (43.0, 467.0) | |
| Blood Loss (mL) | | |
| n | 50 | |

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| | TAG 08-01 Cohort | 95% CI |
| --- | --- | --- |
| Mean (Std Dev) | 246.6 (227.9) | (183.4, 309.8) |
| Median | 200.0 | |
| Range | (10.0, 1000) | |
| **Procedure Survival** | 50 (100.0%) | (92.9%, 100.0%) |
| **Intubation** | | |
| Yes | 47 (94.0%) | |
| No | 3 (6.0%) | |
| **Additional Procedures at Treatment^{1}** | 26 (52.0%) | |
| Surgical Fenestration | 0 (0.0%) | |
| Endovascular Fenestration | 2 (7.7%) | |
| Aortic Stenting | 2 (7.7%) | |
| Peripheral Stenting | 20 (76.9%) | |
| Surgical Bypass | 4 (15.4%) | |
| Angioplasty | 5 (19.2%) | |
| Other Procedure | 6 (23.1%) | |

Confidence Intervals are score intervals for categorical variables, and Wald intervals for continuous variables.

$^{1}$This count used as denominator for percentages under this heading.

Peripheral stenting was defined as a stent or stent graft placed in a vessel branching from the aorta. This can include vessels that come off in the thoracic arch, the mesentery, either of the renal arteries as well as the iliac arteries. The locations of the peripheral stent placements are described in **Table 19**.

Twenty (20) subjects were noted as receiving peripheral stenting. One additional subject (0801-141-008) received a stent in the left carotid artery, but this procedure was categorized by the site into the “Other Procedure” category. For clarity, this subject has been added to the peripheral stenting categorization below. A total of 31 stents (among 28 locations, three classified as “bilateral”) were used in 21 subjects. The specific location, as identified by the site, is reported in **Table 19**.

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**Table 19. Peripheral Stenting Locations**

| Location of Stenting | Number of Locations | Number of Subjects |
| --- | --- | --- |
| Arch Vessel | 4 | 4 |
| Left Carotid | 3 | - |
| Right Innominate | 1 | - |
| Mesenteric | 2 | 2 |
| Celiac | 1 | - |
| Superior Mesenteric | 1 | - |
| Renal | 8 | 8 |
| Left Renal | 2 | - |
| Right Renal | 5 | - |
| Renal | 1 | - |
| Iliac | 14 | 11 |
| Bilateral Iliac | 2 | - |
| Bilateral Common | 1 | - |
| Left Common | 2 | - |
| Left External | 1 | - |
| Left Iliac | 1 | - |
| Right Common | 3 | - |
| Right External | 3 | - |
| Right Iliac | 1 | - |
| Total | 28 | 21 |

Surgical bypasses with their locations are described in **Table 20**. The four subjects with surgical bypasses consist of one femoral-femoral artery bypass and three left carotid-left subclavian artery bypasses.

**Table 20. Surgical Bypass Locations**

| Type of Bypass | Number of Procedures | Number of Subjects |
| --- | --- | --- |
| Left Carotid-Left Subclavian Bypass* | 3 | 3 |
| Femoral-Femoral Artery Bypass | 1 | 1 |
| Total | 4 | 4 |

\* Also reflected in Treatment Characteristics

The locations of the angioplasties observed in this study are described in **Table 21**. Five subjects were noted as receiving angioplasty. One additional subject (0801-134-005) received patch balloon angioplasty to the right common femoral artery, but this procedure was categorized by the site into the 'Other Procedure' category. For clarity, this subject has been added to the categorization of angioplasty below. Six subjects experienced balloon angioplasty in nine locations with five reported in the iliac artery bed, two in the mesenteric bed, and two in the femoral bed. The specific location, as identified by the site, is reported.

All but one subject receiving angioplasty received at least one peripheral stent as discussed previously. The location of balloon angioplasty may be in addition to the location of the peripheral stent or stent graft with some subjects treated in multiple areas of the body.

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**Table 21. Angioplasty Locations**

| Location of Angioplasty | Number of Procedures | Number of Subjects |
| --- | --- | --- |
| Mesenteric | 2 | 2 |
| Celiac | 1 | |
| Superior Mesenteric | 1 | |
| Iliac | 5 | 4 |
| Bilateral Common Iliac | 1 | |
| Left External Iliac | 1 | |
| Left Internal Iliac | 1 | |
| Right Common Iliac | 1 | |
| Right Iliac | 1 | |
| Femoral | 2 | 2 |
| Left Common Femoral | 1 | |
| Right Common Femoral | 1 | |
| Total | 9 | 6 |

Revascularization of the left subclavian artery is characterized in **Table 22** with 75% of subjects receiving no revascularization following coverage.

**Table 22. Summary of Left Subclavian Artery Procedures and Coverage**

| LSA Procedure | LSA COVERAGE | | |
| --- | --- | --- | --- |
| | None | Partial | Complete |
| None | 14(28.0%) | 8(16.0%) | 19(38.0%) |
| Transposed | 0(0.0%) | 0(0.0%) | 2(4.0%) |
| Bypassed | 0(0.0%) | 1(2.0%) | 6(12.0%) |

A summary of convalescence is presented in **Table 23**. Median hospital stay after endovascular treatment with the CTAG Device was 10 days (range 0-41 days). All subjects had an intensive care unit (ICU) stay. The median length of ICU stay was 4.8 days. Hospital survival rate was 92.0%.

**Table 23. Summary of Subject Convalescence**

| | TAG 08-01 Cohort | 95% CI |
| --- | --- | --- |
| Number of Enrolled Subjects | 50 | |
| Hospitalization Duration (Days) | | |
| n | 50 | |
| Mean (Std Dev) | 13.8 (9.8) | (11.1, 16.5) |
| Median | 10 | |
| Range | (0, 41.0) | |
| ICU Stay | | |
| Yes | 50 (100.0%) | (92.9%, 100.0%) |
| No | 0 (0.0%) | |
| ICU Days | | |
| n | 50 | |
| Mean (Std Dev) | 7.6 (7.4) | (5.6, 9.7) |
| Median | 4.8 | |
| Range | (0.0, 31.8) | |
| Intubation | | |
| Yes | 47 (94.0%) | |
| No | 3 (6.0%) | |

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| | TAG 08-01 Cohort | 95% CI |
| --- | --- | --- |
| **Ventilator Days** | | |
| n | 50 | |
| Mean (Std Dev) | 3.7 (5.9) | |
| Median | 1.0 | |
| Range | (0, 26.0) | |
| **Hospital Survival** | 46 (92.0%) | |

## **D. Safety and Effectiveness Results**

### **1. Safety Results**

Gore evaluated the safety of the CTAG Device through collection of site reported adverse events.

#### *Primary Endpoint Analysis*

The primary endpoint for this study was all cause mortality incidence through 30 days post-treatment. The primary endpoint analysis population consisted of all enrolled subjects. Through 30 days post-treatment, a total of four subjects died. Based on this information, there was a probability of 99.8% that the study result met the 30 day mortality performance goal of 25% (**Table 24**). One additional subject was unable to be located or contacted after leaving the hospital against medical advice and was considered a primary endpoint event. Based on five subjects having primary endpoint events, there was a probability of 99.4% that the study result met the 30 day mortality performance goal of 25% (**Table 25**). Because this met the 99% probability threshold, enrollment was concluded with enrollment of 50 subjects due to study success.

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**Table 24. Endpoint Analysis of Known Subjects**

| Enrolled | Eligible for Primary Endpoint Analysis | Number of 30 Day Deaths | 30 Day Mortality Proportion | Protocol Performance Goal | Pr(Mortality×Performance Goal | Data) | Posterior Predictive Probability of Study Success Pr(Success|Data) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 50 | 50 | 4 | 0.0800 | 0.25 | 0.998 | 0.987 |

**Table 25. Endpoint Analysis with Non-Responders**

| Enrolled | Eligible for Primary Endpoint Analysis | Number of 30 Day Deaths | 30 Day Mortality Proportion | Protocol Performance Goal | Pr(Mortality×Performance Goal | Data) | Posterior Predictive Probability of Study Success Pr(Success|Data) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 50 | 50 | 5 | 0.1000 | 0.25 | 0.994 | 0.962 |

# Subject Deaths

Six TAG 08-01 study subjects have died throughout the course of the study. A listing of individual deaths, with their CEC adjudications, is found in **Table 26**.

**Table 26. Death Listing**

| Subject ID | Study Day | Cause of Death | Relationship of Death to Device or Procedure^{1} |
| --- | --- | --- | --- |
| 0801-120-007 | 182 | Acute myocardial infarction | Unrelated to device or endovascular procedure |
| 0801-126-003 | 89 | Aortic dissection rupture | Indeterminate |
| 0801-135-001 | 0 | Aortic dissection | Related to the endovascular procedure |
| 0801-139-001 | 0 | Aortic rupture | Related to the device and the endovascular procedure |
| 0801-141-008 | 5 | Cerebral ischaemia | Unrelated to device or endovascular procedure |
| 0801-181-008 | 3 | Pulmonary embolism | Related to the endovascular procedure |

$^{1}$ As adjudicated by CEC

Subject 0801-126-003 presented to the hospital with complaint of a headache. The subject collapsed and was unable to be revived. The autopsy notes a dissecting rupture of the proximal thoracic arch

Subject 0801-135-001 had a retrograde dissection caused by advancement of device delivery catheter with cardiac arrest resulting shortly thereafter.

Subject 0801-139-001 had an aortic rupture shortly after the procedure due to an inability to obtain seal at the primary entry tear.

Subject 0801-181-008 collapsed during a bowel movement. Pulmonary embolism was confirmed as the cause of death via autopsy.

Although there were some deaths related to the device or the procedure, the overall mortality is low.

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### *Serious Adverse Events*

Site reported serious adverse events (SAEs) reported by the sites in the first 30 days post-procedure are summarized in **Table 27**. Of the subjects that reported an SAE within 30 days post-procedure, 28 (56%) subjects had at least 1 SAE reported and 18 of those subjects had more than 1 SAE reported. **Table 28** provides information on selected 30 Day SAE results from the TAG 08-01 and the SVS MF.

The most common serious adverse event seen in the study was respiratory failure with 14% of subjects experiencing this within 30 days of the procedure. All other adverse events were observed in less than 10% of subjects. The remaining top three frequent adverse events were cerebrovascular accident (characterized by embolic material), pyrexia (post-implant syndrome) and acute renal failure (most likely secondary to presenting aortic dissection). Device specific events such as stent graft endoleak or complication of device catheter removal were each under 5%.

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**Table 27. Summary of Serious Adverse Events through 30 Days**

| | TAG 08-01 Cohort |
| --- | --- |
| **Number of Enrolled Subjects** | 50 |
| **Any Serious Event** | 28(56.0%) |
| Respiratory failure^{1} | 7(14.0%) |
| Cerebrovascular accident^{2,3} | 4(8.0%) |
| Pyrexia^{4} | 4(8.0%) |
| Renal failure acute^{5} | 4(8.0%) |
| Hypertension | 3(6.0%) |
| Hypoxia^{6} | 3(6.0%) |
| Abdominal pain | 2(4.0%) |
| Acute myocardial infarction^{7} | 2(4.0%) |
| Acute respiratory distress syndrome^{8} | 2(4.0%) |
| Acute respiratory failure | 2(4.0%) |
| Aortic dissection^{9} | 2(4.0%) |
| Atrial fibrillation | 2(4.0%) |
| Back pain | 2(4.0%) |
| Gastrointestinal necrosis | 2(4.0%) |
| Hypotension | 2(4.0%) |
| Pleural effusion | 2(4.0%) |
| Sepsis | 2(4.0%) |
| Stent-graft endoleak^{10} | 2(4.0%) |
| Urinary tract infection | 2(4.0%) |
| White blood cell count increased | 2(4.0%) |
| Anaemia | 1(2.0%) |
| Angina pectoris | 1(2.0%) |
| Anuria | 1(2.0%) |
| Aortic rupture^{11} | 1(2.0%) |
| Basal ganglia infarction^{5} | 1(2.0%) |
| Brain oedema^{12} | 1(2.0%) |
| Cardiac failure congestive^{12} | 1(2.0%) |
| Carotid artery occlusion^{12,13} | 1(2.0%) |
| Cerebral ischaemia^{1,12} | 1(2.0%) |
| Compartment syndrome | 1(2.0%) |
| Complication of device removal^{14} | 1(2.0%) |
| Constipation | 1(2.0%) |
| Delirium | 1(2.0%) |
| Delirium tremens | 1(2.0%) |
| Encephalopathy | 1(2.0%) |
| Functional gastrointestinal disorder | 1(2.0%) |
| Groin infection^{12} | 1(2.0%) |
| Haemothorax | 1(2.0%) |
| Hypocalcaemia | 1(2.0%) |
| Ileus | 1(2.0%) |
| Incision site oedema^{12} | 1(2.0%) |
| Incision site pain^{12} | 1(2.0%) |
| Ischaemic hepatitis | 1(2.0%) |
| Ischaemic stroke^{1,12} | 1(2.0%) |
| Labile blood pressure | 1(2.0%) |
| Lactic acidosis | 1(2.0%) |
| Leukocytosis | 1(2.0%) |
| Mental status changes | 1(2.0%) |
| Metabolic acidosis | 1(2.0%) |

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| | TAG 08-01 Cohort |
| --- | --- |
| Monoplegia^{12} | 1(2.0%) |
| Multi-organ failure | 1(2.0%) |
| Muscular weakness^{12} | 1(2.0%) |
| Paraesthesia | 1(2.0%) |
| Paraparesis^{12,15} | 1(2.0%) |
| Peptic ulcer | 1(2.0%) |
| Peripheral artery stenosis | 1(2.0%) |
| Pneumonia | 1(2.0%) |
| Pulmonary bulla | 1(2.0%) |
| Pulmonary embolism^{12} | 1(2.0%) |
| Pulmonary hypertension | 1(2.0%) |
| Pulmonary oedema^{12} | 1(2.0%) |
| Renal failure | 1(2.0%) |
| Renal failure chronic | 1(2.0%) |
| Spinal cord ischaemia^{15} | 1(2.0%) |
| Troponin increased | 1(2.0%) |
| Unresponsive to stimuli | 1(2.0%) |
| Vomiting | 1(2.0%) |

$^{1}$Two of these events were adjudicated by the CEC to be related to the endovascular procedure

$^{2}$All four of these events were adjudicated by the CEC to be related to the endovascular procedure

$^{3}$Identified as stroke; additional information on all stroke events is provided below in the *Additional Adverse Event Information* section.

$^{4}$Two of these events were adjudicated by the CEC to be related to the endovascular procedure

$^{5}$Two of these events were adjudicated by the CEC to be related to the endovascular procedure; it is unknown if the events were related to contrast dye

$^{6}$One of these events was adjudicated by the CEC to be related to the endovascular procedure

$^{7}$One of these events was adjudicated by the CEC to be related to the endovascular procedure

$^{8}$One of these events was adjudicated by the CEC to be related to the endovascular procedure

$^{9}$Additional information on all progressive aortic dissection events is provided below in the *Additional Adverse Event Information* section; one event was CEC adjudicated as related to the endovascular procedure; one event was CEC adjudicated as related to both the device and endovascular procedure

$^{10}$Additional information on stent graft endoleaks available in **Table 44** Major Device Events by Follow-Up Period; one Type IA endoleak was CEC adjudicated as related to both the device and endovascular procedure; the other event was reported by the site as persistent blood flow in the false lumen was determined by the CEC to be unrelated to device or endovascular procedure

$^{11}$Additional information on rupture events available in **Table 43** Aortic Rupture Events

$^{12}$This event was adjudicated by the CEC to be related to the endovascular procedure

$^{13}$Following device deployment, a hemodynamic compromise was observed; a stent was deployed in the left common carotid artery to ensure vessel patency

$^{14}$Additional information on the complication of device removal is available in **Table 44**; this event was adjudicated by the CEC to be related to both the device and endovascular procedure

$^{15}$Additional information on paraparesis and spinal cord ischaemia events is provided below in the *Additional Adverse Event Information* section;

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Table 28. Selected 30 Day SAE Results from TAG 08-01 and the SVS MF

| | TAG 08-01 Cohort | SVS MF Cohort |
| --- | --- | --- |
| Number of Enrolled Subjects | 50 | 85 |
| Any Event | 20(40.0%) | 32(37.6%) |
| Death | 4(8.0%) | 9(10.6%) |
| MI | 2(4.0%) | 1(1.2%) |
| Stroke1 | 7(14.0%) | 8(9.4%) |
| Renal Failure (+Dialysis) | 3(6.0%) | 8(9.4%) |
| Respiratory Failure (with Ventilation) | 9(18.0%) | 2(2.4%) |
| Paralysis/Paraparesis | 3(6.0%) | 8(9.4%) |
| Bowel Ischemia | 2(4.0%) | 3(3.5%) |

Two non-serious strokes were excluded from TAG 08-01 cohort as the SVS Publication only included serious strokes.

Sites were instructed to report and classify severity of all adverse events as shown in Table 29.

Table 29. Serious Adverse Events by Follow-Up Period

| | Post-Treatment Follow-up Period | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Procedure | Post-Procedure | 1 Month | 6 Months | 12 Months | 24 Months |
| Blood and lymphatic system disorders | 0(0.0%) | 1(2.1%) | 1(2.2%) | 1(2.2%) | 0(0.0%) | 2(9.1%) |
| Anaemia | - | 1(2.1%) | - | - | - | 2(9.1%) |
| Disseminated intravascular coagulation | - | - | - | 1(2.2%) | - | - |
| Leukocytosis | - | - | 1(2.2%) | - | - | - |
| Metabolism and nutrition disorders | 2(4.0%) | 1(2.1%) | 0(0.0%) | 1(2.2%) | 0(0.0%) | 0(0.0%) |
| Lactic acidosis | 1(2.0%) | - | - | - | - | - |
| Metabolic acidosis | 1(2.0%) | - | - | - | - | - |
| Hypocalcaemia | - | 1(2.1%) | - | - | - | - |
| Gout | - | - | - | 1(2.2%) | - | - |

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| | Post-Treatment Follow-up Period | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Procedure | Post-Procedure | 1 Month | 6 Months | 12 Months | 24 Months |
| **Psychiatric disorders** | 0(0.0%) | 3(6.3%) | 0(0.0%) | 1(2.2%) | 0(0.0%) | 0(0.0%) |
| Delirium | - | 1(2.1%) | - | - | - | - |
| Delirium tremens | - | 1(2.1%) | - | - | - | - |
| Depression | - | - | - | 1(2.2%) | - | - |
| Mental status changes | - | 1(2.1%) | - | - | - | - |
| **Nervous system disorders** | 4(8.0%) | 8(16.7%) | 1(2.2%) | 1(2.2%) | 2(4.8%) | 1(4.5%) |
| Cerebrovascular accident | 0(0.0%) | 4(8.3%) | - | - | - | - |
| Basal ganglia infarction | 0(0.0%) | 1(2.1%) | - | - | - | - |
| Carotid artery occlusion | 1(2.0%) | 0(0.0%) | - | - | - | - |
| Cerebral ischaemia | 0(0.0%) | 1(2.1%) | - | - | - | - |
| Ischaemic stroke | 0(0.0%) | 1(2.1%) | - | - | - | - |
| Spinal cord ischaemia | 1(2.0%) | - | - | 1(2.2%) | - | 0(0.0%) |
| Spinal cord infarction | 0(0.0%) | - | - | 0(0.0%) | - | 1(4.5%) |
| Monoplegia | 0(0.0%) | 1(2.1%) | - | - | - | - |
| Paraparesis | 1(2.0%) | 0(0.0%) | - | - | - | - |
| Encephalopathy | - | 1(2.1%) | - | - | - | - |
| Brain oedema | - | 1(2.1%) | - | - | - | - |
| Unresponsive to stimuli | - | - | 1(2.2%) | - | - | - |
| Paraesthesia | 1(2.0%) | - | - | - | - | - |
| Convulsion | - | - | - | - | 1(2.4%) | - |
| Brain injury | - | - | - | - | 1(2.4%) | - |
| **Cardiac disorders** | 0(0.0%) | 4(8.3%) | 0(0.0%) | 5(11.1%) | 4(9.5%) | 2(9.1%) |
| Angina pectoris | - | 1(2.1%) | - | 3(6.7%) | 3(7.1%) | 1(4.5%) |
| Acute myocardial infarction | - | 2(4.2%) | - | 1(2.2%) | 0(0.0%) | 0(0.0%) |
| Cardiac failure congestive | - | 1(2.1%) | - | - | - | 1(4.5%) |
| Atrial fibrillation | - | 2(4.2%) | - | - | - | - |

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| | Post-Treatment Follow-up Period | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Procedure | Post-Procedure | 1 Month | 6 Months | 12 Months | 24 Months |
| Cardiac arrest | - | - | - | 1(2.2%) | 1(2.4%) | - |
| **Vascular disorders** | 3(6.0%) | 6(12.5%) | 1(2.2%) | 3(6.7%) | 0(0.0%) | 3(13.6%) |
| Aortic aneurysm | 0(0.0%) | 0(0.0%) | 1(2.2%) | 0(0.0%) | - | 1(4.5%) |
| Aortic dissection | 1(2.0%) | 1(2.1%) | 0(0.0%) | 0(0.0%) | - | 0(0.0%) |
| Aortic dissection rupture | 0(0.0%) | 0(0.0%) | 0(0.0%) | 1(2.2%) | - | 0(0.0%) |
| False lumen dilatation of aortic dissection | 0(0.0%) | 0(0.0%) | 0(0.0%) | 0(0.0%) | - | 1(4.5%) |
| Hypertension | - | 3(6.3%) | - | - | - | - |
| Hypotension | - | 2(4.2%) | - | - | - | - |
| Accelerated hypertension | - | - | - | - | - | 1(4.5%) |
| Labile blood pressure | - | 1(2.1%) | - | - | - | - |
| Haemorrhage | - | - | - | 1(2.2%) | - | - |
| Deep vein thrombosis | - | - | - | 1(2.2%) | - | - |
| Peripheral artery stenosis | 1(2.0%) | - | - | - | - | - |
| Aortic rupture | 1(2.0%) | - | - | - | - | - |
| **Respiratory, thoracic and mediastinal disorders** | 3(6.0%) | 13(27.1%) | 1(2.2%) | 1(2.2%) | 1(2.4%) | 2(9.1%) |
| Respiratory failure | - | 7(14.6%) | - | 1(2.2%) | - | - |
| Acute respiratory failure | - | 2(4.2%) | - | 0(0.0%) | - | - |
| Pleural effusion | 1(2.0%) | 1(2.1%) | - | - | - | 1(4.5%) |
| Haemothorax | 0(0.0%) | 1(2.1%) | - | - | - | 0(0.0%) |
| Pneumothorax | 0(0.0%) | 0(0.0%) | - | - | - | 1(4.5%) |
| Hypoxia | - | 2(4.2%) | 1(2.2%) | - | 1(2.4%) | - |
| Acute respiratory distress syndrome | 1(2.0%) | 1(2.1%) | - | - | - | - |
| Pulmonary oedema | 0(0.0%) | 1(2.1%) | - | - | - | - |
| Pneumonitis | - | - | - | - | 1(2.4%) | - |
| Pulmonary bulla | 1(2.0%) | - | - | - | - | - |

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| | Post-Treatment Follow-up Period | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Procedure | Post-Procedure | 1 Month | 6 Months | 12 Months | 24 Months |
| Pulmonary hypertension | - | 1(2.1%) | - | - | - | - |
| Pulmonary embolism | - | 1(2.1%) | - | - | - | - |
| **Gastrointestinal disorders** | 2(4.0%) | 4(8.3%) | 2(4.4%) | 2(4.4%) | 1(2.4%) | 2(9.1%) |
| Abdominal pain | - | 1(2.1%) | 1(2.2%) | 1(2.2%) | - | - |
| Haematemesis | - | - | 0(0.0%) | 1(2.2%) | - | 0(0.0%) |
| Lower gastrointestinal haemorrhage | - | - | 0(0.0%) | 0(0.0%) | - | 1(4.5%) |
| Upper gastrointestinal haemorrhage | - | - | 1(2.2%) | 0(0.0%) | - | 0(0.0%) |
| Gastrointestinal necrosis | - | 2(4.2%) | - | - | - | - |
| Ileus | 1(2.0%) | - | - | - | - | 1(4.5%) |
| Vomiting | - | - | 1(2.2%) | - | 1(2.4%) | 1(4.5%) |
| Nausea | - | - | 0(0.0%) | - | 1(2.4%) | 0(0.0%) |
| Pancreatitis | - | - | 1(2.2%) | - | - | - |
| Small intestinal obstruction | - | - | - | 1(2.2%) | - | - |
| Abdominal distension | - | - | - | - | - | 1(4.5%) |
| Constipation | - | - | 1(2.2%) | - | - | - |
| Functional gastrointestinal disorder | 1(2.0%) | - | - | - | - | - |
| Peptic ulcer | - | 1(2.1%) | - | - | - | - |
| **Hepatobiliary disorders** | 1(2.0%) | 0(0.0%) | 0(0.0%) | 0(0.0%) | 0(0.0%) | 0(0.0%) |
| Ischaemic hepatitis | 1(2.0%) | - | - | - | - | - |
| **Musculoskeletal and connective tissue disorders** | 2(4.0%) | 0(0.0%) | 2(4.4%) | 1(2.2%) | 0(0.0%) | 2(9.1%) |
| Back pain | - | - | 2(4.4%) | - | - | 1(4.5%) |
| Haemarthrosis | - | - | - | 1(2.2%) | - | - |
| Muscular weakness | 1(2.0%) | - | - | - | - | - |
| Compartment syndrome | 1(2.0%) | - | - | - | - | - |

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| | Post-Treatment Follow-up Period | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Procedure | Post-Procedure | 1 Month | 6 Months | 12 Months | 24 Months |
| Osteoarthritis | - | - | - | - | - | 1(4.5%) |
| Renal and urinary disorders | 2(4.0%) | 3(6.3%) | 2(4.4%) | 0(0.0%) | 0(0.0%) | 1(4.5%) |
| Renal failure acute | 1(2.0%) | 3(6.3%) | 1(2.2%) | - | - | 0(0.0%) |
| Anuria | 1(2.0%) | 0(0.0%) | 0(0.0%) | - | - | 0(0.0%) |
| Renal failure | 1(2.0%) | 0(0.0%) | 0(0.0%) | - | - | 0(0.0%) |
| Renal failure chronic | 0(0.0%) | 0(0.0%) | 1(2.2%) | - | - | 0(0.0%) |
| Renal impairment | 0(0.0%) | 0(0.0%) | 0(0.0%) | - | - | 1(4.5%) |
| General disorders and administration site conditions | 2(4.0%) | 6(12.5%) | 1(2.2%) | 1(2.2%) | 0(0.0%) | 0(0.0%) |
| Pyrexia | - | 4(8.3%) | - | - | - | - |
| Stent-graft endoleak | 1(2.0%) | 1(2.1%) | 1(2.2%) | 1(2.2%) | - | - |
| Complication of device removal | 1(2.0%) | - | - | - | - | - |
| Multi-organ failure | - | 1(2.1%) | - | - | - | - |
| Investigations | 0(0.0%) | 2(4.2%) | 1(2.2%) | 0(0.0%) | 0(0.0%) | 0(0.0%) |
| White blood cell count increased | - | 1(2.1%) | 1(2.2%) | - | - | - |
| Troponin increased | - | 1(2.1%) | - | - | - | - |
| Injury, poisoning and procedural complications | 0(0.0%) | 2(4.2%) | 0(0.0%) | 2(4.4%) | 0(0.0%) | 0(0.0%) |
| Incision site oedema | - | 1(2.1%) | - | - | - | - |
| Incision site pain | - | 1(2.1%) | - | - | - | - |
| Vascular pseudoaneurysm | - | - | - | 1(2.2%) | - | - |
| Lumbar vertebral fracture | - | - | - | 1(2.2%) | - | - |

Note: Column header counts and denominators are the number of subjects at risk at the start of each interval. Entries represent MedRA SOC, HLT and PT and are identified by increasing level of indentation.

Study period definitions: Procedure(0-0 days) Post-Procedure(1-14 days) 1 Month(15-59 days) 6 Months(60-242 days) 12 Months(243-546 days) 24 Months(547-911 days)

MedDRA Version: V15.1

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### *Additional Adverse Event Information*

In order to provide further clarity on adverse events of particular interest in the setting of endovascular treatment of acute complicated Type B aortic dissection, further detailed information has been compiled on stroke, spinal cord ischemia, and aortic dissection events subsequent to the initial endovascular procedure.

### Stroke

Stroke (regardless of severity status) was reported in 9 subjects in the TAG 08-01 study (18%): all occurring within the first 30 days after treatment. Seven of these were classified as serious events and were reported in **Tables 27 and 29** as cerebrovascular accident, basal ganglia infarction, cerebral ischemia, or ischemic stroke. Events classified as stroke could have been identified by clinical symptoms that may or may not have included a follow-up evaluation by a neurologist, radiographic imaging or a combination of both types of assessments. Adverse event descriptions, as reported by the investigational sites, with Investigator evaluated event severities and the corresponding CEC adjudications are provided in **Table 30**.

**Table 30. Stroke Data**

| Subject Number | Event Day | Adverse Event Description | Serious Non-serious | CEC Adjudication |
| --- | --- | --- | --- | --- |
| 0801-103-002 | 10 | Age indeterminate infarct of right cerebellum and basal ganglia | Serious | Unrelated to device or endovascular procedure |
| 0801-112-005 | 6 | Multiple brain infarcts | Non-serious | Related to the endovascular procedure |
| 0801-120-003 | 2 | Cerebrovascular accident | Serious | Related to the endovascular procedure |
| 0801-134-005 | 5 | Intraventricular hemorrhage | Non-serious | Unrelated to device or endovascular procedure |
| 0801-141-008 | 5 | Diffuse cerebral anoxic ischemic injury | Serious | Related to the endovascular procedure |
| 0801-146-002 | 1 | Ischemic changes in left frontal and occipital lobes of brain without hemorrhage consistent with stroke | Serious | Related to the endovascular procedure |
| 0801-178-001 | 9 | Stroke | Serious | Related to the endovascular procedure |
| 0801-306-003 | 1 | Bilateral strokes | Serious | Related to the endovascular procedure |
| 0801-361-021 | 1 | CVA due to multiple embolic infarctions through out the brain bilaterally without hemorrhage. | Serious | Related to the endovascular procedure |

An independent review of the stroke events was conducted by two neurologists as part of the study's CEC. Using site provided source documentation, they assessed events for the type of stroke observed, the presence of confounding factors potentially contributing to the event, the status of event symptoms at time of discharge, the status of event symptoms at time of the last available follow-up visit, and evaluated the overall impact the event had on subject functional outcomes. Functional outcome was defined as event impact in terms of altering the ability for the subject to carry out normal daily activities in the medical

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opinion of the CEC neurologists. A summary of their findings can be found in Table 31.

Table 31. CEC Neurologist Stroke Review

| Subject Number | Stroke Type | Confounding Event Factors | Improvement-Discharge | Improvement-Follow-up | Impact on Functional Outcome |
| --- | --- | --- | --- | --- | --- |
| 0801-103-002 | Ischemic-Embolic | ICU delirium/medications | Yes-Full | N/A- Insufficient information | None |
| 0801-112-005 | Ischemic-Embolic | Hypoxia | Yes-Full | Yes-Full | None |
| 0801-120-003 | Ischemic-Embolic | Questionable occlusion of left subclavian and vertebral arteries | Yes-Partial | Yes-Partial | Moderate |
| 0801-134-005 | Hemorrhagic | Heparin-during procedure | Yes-Full | Yes-Full | None^{1} |
| 0801-141-008 | Ischemic-hemodynamic/perfusional in origin | None | N/A- Death | N/A- Death | Severe |
| 0801-146-002 | Ischemic-Embolic | None | Yes-Partial | Yes-Full | None |
| 0801-178-001 | Ischemic-Embolic | Retrograde ascending aortic dissection | Yes-Partial | Yes-Full | None |
| 0801-306-003 | Ischemic-Embolic | Diffuse atherosclerotic arch | Yes-Partial | Yes-Full | None |
| 0801-361-021 | Ischemic-Embolic | None | Yes-Partial | Yes-Full | None^{1} |

$^{1}$ A functional limitation is present but related to a spinal cord infarction that occurred either before or after the procedure.

Of the nine neurological events that were reviewed by the CEC subcommittee, eight were characterized as ischemic in nature, with one as hemorrhagic. Of the ischemic strokes, all…