VALIANT THORACIC STENT GRAFT WITH CAPTIVIA DELIVERY SYSTEM
Device Facts
| Record ID | P100040S012 |
|---|---|
| Device Name | VALIANT THORACIC STENT GRAFT WITH CAPTIVIA DELIVERY SYSTEM |
| Applicant | Medtronic Vascular |
| Product Code | MIH · Cardiovascular |
| Decision Date | Jan 22, 2014 |
| Decision | APPR |
| Device Class | Class 3 |
| Attributes | Therapeutic, Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| P100040S012 · Jan 22, 2014 | VALIANT THORACIC STENT GRAFT WITH CAPTIVIA DELIVERY SYSTEM | Medtronic Vascular | Society for Vascular Surgery (SVS) Master Access File (MAF); VIRTUE study (observational registry); Valiant Captivia OUS post-market registry; TRAVIATA study (retrospective data review) | Retrospective registry and clinical data were used to establish performance goals for the primary clinical trial and to provide supplemental safety and effectiveness evidence for the expanded indication to include Type B dissections. | Performance Goal; Registry; Retrospective Review; Supplemental Evidence |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| SVS Master Access File (MAF); Retrospective registry/database | 85 acute, complicated dissection subjects; Sample Size: 85 | Not applicable for this study | 30-day mortality rate |
| VIRTUE, Valiant Captivia OUS, and TRAVIATA studies; Observational registries and retrospective data review; Follow-up/Duration: 1 to 3 years | Patients with Type B dissection treated with Valiant device; Sample Size: Approximately 175; Number of Sites: Multiple (e.g., 4 German centers for TRAVIATA) | Not applicable for this study | Safety and clinical performance (mortality, retrograde Type A dissection, paralysis, stroke) |
Indications for Use
The Valiant Thoracic Stent Graft with the Captivia Delivery System is intended for the endovascular repair of all lesions of the descending thoracic aorta (DTA) in patients having appropriate anatomy including: iliac/femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories; non-aneurysmal aortic diameter in the range of 18–42 mm (fusiform and saccular aneurysms/penetrating ulcers), 18 mm to 44 mm (blunt traumatic aortic injuries) or 20 mm to 44 mm (dissections) and non-aneurysmal aortic proximal and distal neck lengths ≥20 mm (fusiform and saccular aneurysms/penetrating ulcers), landing zone ≥20 mm proximal to the primary entry tear (BTAI, dissection). The proximal extent of the landing zone must not be dissected.
Device Story
Endovascular stent graft system for descending thoracic aorta (DTA) lesions; delivered via femoral/iliac artery access using Captivia delivery system; self-expanding nitinol scaffold with polyester fabric; deployed under fluoroscopic guidance; proximal/distal ends conform to aortic seal zones; used by vascular surgeons/interventionalists in hospital setting; provides endoluminal exclusion of lesions (aneurysms, dissections, traumatic injuries); promotes false lumen thrombosis and aortic remodeling; reduces mortality/morbidity compared to open surgical repair.
Clinical Evidence
Prospective, non-randomized, multicenter study (Medtronic Dissection Trial) of 50 patients with acute, complicated Type B dissection. Primary endpoint: 30-day all-cause mortality (8.0%, 95% UCL 17.4%), meeting 25% performance goal. Secondary endpoints included technical success (100%), aortic remodeling, and adverse events. Data supported by VALOR II and RESCUE studies.
Technological Characteristics
Self-expanding tube endoprosthesis; polyester graft fabric; nitinol wire spring scaffold; platinum-iridium radiopaque markers; modular configuration; delivery via Captivia catheter (tip capture or non-tip capture); standalone device; non-implantable delivery system; biocompatible materials.
Indications for Use
Indicated for endovascular repair of all lesions of the descending thoracic aorta (DTA) in patients ≥18 years with appropriate anatomy, including fusiform/saccular aneurysms, penetrating ulcers, blunt traumatic aortic injuries, and Type B dissections. Contraindicated in patients with systemic infection or known sensitivities/allergies to device materials.
Reference Devices
Submission Summary (Full Text)
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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)
## I. GENERAL INFORMATION
Device Generic Name: Endovascular Graft
Device Trade Name: Valiant® Thoracic Stent Graft with the Captivia® Delivery System
Device Procode: MIH
Applicant's Name and Address: Medtronic Vascular
3576 Unocal Place
Santa Rosa, CA 95403
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P100040/S012
Date of FDA Notice of Approval: January 22, 2014
Priority Review: Not Applicable
The Valiant® Thoracic Stent Graft with the Captivia® Delivery System original PMA (P100040) was approved on April 1, 2011 for the endovascular repair of fusiform aneurysms and saccular aneurysms/penetrating ulcers of the descending thoracic aorta (DTA). The indications for use were expanded to include the treatment of isolated lesions (excluding dissections) of the DTA in patients who have appropriate anatomy via P100040/S008 on October 26, 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 Valiant® Thoracic Stent Graft with the Captivia® Delivery System to include the treatment of all lesions of the DTA, including Type B dissections.
## II. INDICATIONS FOR USE
The Valiant® Thoracic Stent Graft with the Captivia® Delivery System is intended for the endovascular repair of all lesions of the descending thoracic aorta (DTA) in patients having appropriate anatomy including:
- iliac/femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories;
- non-aneurysmal aortic diameter in the range of 18–42 mm (fusiform and saccular aneurysms/penetrating ulcers), 18 mm to 44 mm (blunt traumatic aortic injuries) or 20 mm to 44 mm (dissections) and
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• non-aneurysmal aortic proximal and distal neck lengths ≥20 mm (fusiform and saccular aneurysms/penetrating ulcers), landing zone ≥20 mm proximal to the primary entry tear (BTAI, dissection). The proximal extent of the landing zone must not be dissected.
### III. CONTRAINDICATIONS
The Valiant thoracic stent graft with the Captivia delivery system is contraindicated in the following patient populations:
- Patients who have a condition that threatens to infect the graft
- Patients with known sensitivities or allergies to the device materials
### IV. WARNINGS AND PRECAUTIONS
The warnings and precautions can be found in the Valiant Thoracic Stent Graft with Captivia Delivery System Instructions for Use.
### V. DEVICE DESCRIPTION
#### Valiant Thoracic Stent Graft with the Captivia Delivery System
The Valiant Thoracic Stent Graft with the Captivia Delivery System is comprised of two components:
Valiant Thoracic Stent Graft
Captivia Delivery System
The Valiant Thoracic Stent Graft is intended to be delivered endoluminally via access through the femoral or iliac artery to the site of the lesion using the Captivia Delivery System. The stent graft is loaded into and constrained by the delivery system outer sheath (graft cover). The pre-loaded stent graft is advanced to the lesion location over a guidewire. Upon deployment, the stent graft self-expands due to the superelastic properties of the nitinol stent. The proximal and distal ends of the stent graft are intended to conform to the shape and size of the proximal and distal seal zones of the targeted lesion due to the radial force of the stents.
#### Valiant Thoracic Stent Graft
The Valiant Thoracic Stent Graft is a self-expanding, tube endoprosthesis composed of a polyester graft fabric and a spring scaffold made from nitinol wire. The metal scaffolding is composed of a series of serpentine springs stacked in a tubular configuration. The springs are sewn onto a polyester fabric with non-absorbable polyester sutures.
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Platinum-Iridium radiopaque markers are sewn to the fabric to facilitate radiographic visualization of the edge of the graft material and the minimum overlap required when multiple stent grafts are used. The four proximal Figur8 markers (shaped as a figure 8), and the two distal Zer0 markers (shaped as a Zero), indicate the extremities of the covered stent graft. The single Figur8 “mid-marker” indicates the minimum amount of overlap required for multiple components.
During manufacturing, the Valiant Thoracic Stent Graft is preloaded into a delivery system.
See Figure 1 for a drawing of the Valiant Thoracic Stent Graft.
## Valiant Thoracic Stent Graft Configuration and Placement
The Valiant Thoracic Stent Graft is a modular device that accommodates the use of additional sections depending on the configuration of the anatomy where single or multiple components may be required to achieve sufficient coverage of the lesion.
If the vessel diameter and condition require variable proximal and distal diameter devices, the smallest diameter stent graft should be placed first, either at the proximal or distal end of the lesion, as appropriate. The additional section is to be deployed within the primary piece following the oversizing requirements, as detailed in the Instructions for Use (IFU) manual.
If the vessel diameter and condition require the same proximal and distal diameter devices, the primary section should be placed at the proximal end of the lesion. To achieve the same final diameter with the proximal and distal sections, a tapered configuration is required for the distal section. The flare of the tapered graft permits the over sizing requirements between components to maintain connection between primary and additional sections.
Different end configurations are available to further accommodate anatomical dimensions. The proximal end comes in two configurations: FreeFlo or Closed Web (Figure 1). Devices with a FreeFlo proximal end configuration have a bare spring extending beyond the edge of the fabric at the proximal end of the stent graft and should be implanted in the most proximal position only. The Closed Web proximal end configuration, which has a covered spring at the proximal end of the stent graft, is implanted distally. The distal end configurations of the stent grafts are Closed Web or Bare Spring. The Closed Web distal end configuration has a covered spring at the distal end of the stent graft. The Bare Spring distal end configuration has a bare spring at the distal end of the stent graft that extends beyond the edge of the fabric.
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FreeFlo Straight
(Proximal Component)
Distal Bare Spring
Straight (Distal Component)
1. Proximal End
2. Distal End
3. FreeFlo
4. Closed Web
5. Bare Spring
6. Mini Support Spring
7. Figure8 Marker
8. Zer0 Marker
9. Diameter
10. Covered Length
11. Total Length
Closed Web Straight
(Distal Component)
Closed Web Taper
(Distal Component)
**Figure 1. Valiant Thoracic Stent Graft End Configurations**
NOTE: This and all other product graphics appearing in this summary are not drawn to scale, are for graphical representation only, and may appear differently under fluoroscopy.
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## Captivia Delivery System
The Captivia Delivery System consists of a single use, disposable catheter with an integrated handle to provide the user with controlled deployment. The Captivia Delivery System (Figure 2) is the generic name for the following two delivery system configurations:
The FreeFlo Stent Graft Delivery System (Tip Capture)
The Closed Web Stent Graft Delivery System (non-Tip Capture)
## FreeFlo Stent Graft Delivery System
The FreeFlo Stent Graft Delivery System is used with the FreeFlo Straight configuration, the stent graft configuration that is implanted in the most proximal position. The delivery system features a tip capture mechanism from which the proximal stent graft is deployed in two stages:
(1) Deployment of the stent graft with the apices of the bare spring of the FreeFlo configuration still constrained by the tip capture mechanism; and
(2) Release of the proximal bare spring.
## Closed Web Stent Graft Delivery System
The Closed Web Stent Graft Delivery System is used with the Closed Web Straight, Distal Bare Spring Straight, and Closed Web Tapered configuration stent grafts. The Closed Web Delivery System does not include a tip capture mechanism because these devices do not have a bare spring configuration at the proximal end of the stent graft. As a result, deployment using the Closed Web Delivery System is accomplished in a single step when the outer sheath is removed from the stent graft.
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Figure 2. Captivia Delivery System
(The FreeFlo Stent Graft Delivery System on Top, Closed Web Stent Graft Delivery System on Bottom)
## 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.
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Alternative practices and procedures used in the treatment of Type B aortic dissection can involve an open surgical thoracic aortic graft repair, interventional or surgical flap fenestration and true lumen stenting, catheter reperfusion or extra-anatomic surgical bypass. The goal of both thoracic endovascular aortic repair (TEVAR) and open surgical treatment is to seal, or resect the intimal tear, thus depressurizing and shrinking the false lumen with subsequent aortic remodeling and aortic stabilization. Due to high mortality rates and associated complications with the alternative practices listed above, the treatment of acute complicated dissections has shifted to thoracic endovascular aortic repair (TEVAR).
### VII. MARKETING HISTORY
The Valiant Thoracic Stent Graft with the Captivia Delivery System originally received premarket approval for use in the treatment of aneurysms of the DTA on April 1, 2011. Subsequently, the Valiant Thoracic Stent Graft with Captivia Delivery system received FDA approval for the endovascular repair of isolated lesions of the DTA (excluding dissections) on October 26, 2012.
The Valiant Thoracic Stent Graft with the Captivia Delivery System has been commercially available for distribution outside of the United States since October 2009. It is commercially available in Argentina, Australia, Belarus, Belize, Bosnia-Herzegovina, Brazil, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, Egypt, El Salvador, the European Union, Guatemala, Honduras, Hong Kong, Hungary, India, Israel, Japan, Kazakhstan, Kuwait, Macedonia, Malaysia, Mexico, Montenegro / Serbia, New Zealand, Nicaragua, Panama, Peru, Puerto Rico, Romania, Russia, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, South Korea, Taiwan, Thailand, Turkey, Ukraine, Uruguay, US, Venezuela and Vietnam.
The Valiant Thoracic Stent Graft with the Captivia Delivery System has not been withdrawn from the market for any reason related to safety or effectiveness.
### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH
Below is a list of the potential adverse effects (e.g., complications) that may be associated with the use of the device.
Table 1. Potential Adverse Effects
| Access failure | Endoleaks | Post-procedural bleeding |
| --- | --- | --- |
| Adynamic Ileus | Excessive or inappropriate radiation exposure | Procedural bleeding |
| Allergic reaction (to contrast, anti-platelet therapy, stent graft material) | Extrusion/erosion | Prosthesis dilatation |
| Amputation | Failure to deliver the stent graft | Prosthesis infection |
| Anesthetic complications | Femoral neuropathy | Prosthesis rupture |
| Aortic expansion (e.g. | Fistula (aortoenteric, | Prosthesis thrombosis |
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| aneurysm, false lumen) | arteriovenous, aortoesophageal, aortobronchial) | |
| --- | --- | --- |
| Aneurysm rupture | Gastrointestinal bleeding/complications | Pseudoaneurysm |
| Angina | Genitourinary complications | Pulmonary edema |
| Arrhythmia | Hematoma | Pulmonary embolism |
| Arterial Stenosis | Hemorrhage/bleeding | Reaction to anaesthesia |
| Atelectasis | Hypotension/hypertension | Renal failure |
| Blindness | Infection or fever | Renal insufficiency |
| Bowel ischemia | Insertion or removal difficulty | Reoperation |
| Bowel necrosis | Intercostal pain | Respiratory depression or failure |
| Bowel obstruction | Intramural hematoma | Retrograde Type A dissection |
| Branch vessel occlusion | Leg edema/foot edema | Sepsis |
| Breakage of the metal portion of the device | Lymphocele | Seroma |
| Buttock claudication | Myocardial infarction | Shock |
| Cardiac tamponade | Nerve injury | Spinal neurological deficit |
| Catheter breakage | Neuropathy | Stent graft migration |
| Cerebrovascular accident (CVA) | Occlusion – Venous or Arterial | Stent graft misplacement |
| Change in mental status | Pain/Reaction at catheter insertion site | Stent graft occlusion |
| Coagulopathy | Paralysis | Stent graft twisting or kinking |
| Congestive heart failure | Paraparesis | Transient-ischemic attack (TIA) |
| Contrast toxicity | Paraplegia | Thrombosis |
| Conversion to surgical repair | Paresthesia | Tissue necrosis |
| Damage to the vessel which may require a conversion to open repair | Perfusion of the false lumen | Vascular ischemia |
| Death | Peripheral ischemia | Vascular trauma |
| Deployment difficulties/failures | Peripheral nerve injury | Wound healing complications |
| Dissection, perforation, or rupture of the aortic vessel & surrounding vasculature | Pneumonia | Wound infection |
| Embolism | Post-implant syndrome | Wound dehiscence |
## IX. SUMMARY OF PRECLINICAL STUDIES
The SSEDs containing the pre-clinical studies to support the aneurysm indication (the original Valiant Thoracic Stent Graft PMA (P100040)) and the indication for isolated lesions (excluding dissections) (P100040/S008) are available on the CDRH website.
Medtronic is seeking approval of an expanded indication using the same commercially approved Valiant Thoracic Stent Graft with the Captivia delivery System. No changes
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have been made to the product design or specifications. All pre-clinical studies previously provided in P100040 and P100040/S008 are applicable to and support the use of the Valiant Thoracic Stent Graft with the Captivia Delivery System in the endovascular treatment of Type B dissection of the DTA under this Supplement.
# X. SUMMARY OF PRIMARY CLINICAL STUDY
One primary clinical study (the Medtronic Dissection Trial) was conducted to support the expansion of the Valiant Captivia indications for use to include all lesions of the descending thoracic aorta (DTA), under IDE G090199. Key characteristics of the clinical study are provided in Table 2.
The safety and effectiveness of the Valiant Thoracic Stent Graft for lesions of the DTA was not based on the Medtronic Dissection Trial alone, but rather on all available data for the Valiant Thoracic Stent Graft to date, including data from the aneurysm clinical study (VALOR II), reviewed under PMA P100040, and the blunt traumatic aortic injury (BTAI) clinical study (RESCUE), reviewed under PMA-S P10040/S008. 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. Summary of Clinical Study
| Clinical Study | Study Design | Objective | Number of Sites with Enrollments | Number of Subjects |
| --- | --- | --- | --- | --- |
| Medtronic Dissection Trial | Prospective, non-randomized, multicenter study to evaluate the clinical performance of Valiant Captivia in the treatment of acute, complicated Type B dissection. The primary endpoint was all-cause mortality within 30 days of the index procedure. Several secondary observations of safety and effectiveness were assessed using descriptive statistics. | To evaluate the safety and effectiveness of Valiant Captivia in the treatment of subjects with acute, complicated Type B dissection, as determined by all-cause mortality within 30 days of the index procedure. | 16 | 50 |
# A. Study Design
The Medtronic Dissection Trial was a was a prospective, non-randomized, multicenter study to evaluate the clinical performance of the Valiant Thoracic Stent Graft for treatment of acute, complicated Type B dissection. Patients were treated between June 25, 2010 and May 8, 2012. The database for this summary reflected
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data collected through May 30, 2013 and included 50 patients. There were 16 investigational sites. The primary objective was to evaluate the safety and effectiveness of the Valiant Thoracic Stent Graft in the treatment of acute, complicated Type B dissection, as determined by all-cause mortality within 30 days of the index procedure.
The primary hypothesis of the study was that all-cause mortality through 30 days post-treatment met the performance goal of 25%. An adaptive design was utilized such that additional subject enrollment (up to 84 subjects total) would be allowed as necessary to meet the performance goal. However, the performance goal was met after evaluation of the primary endpoint for the initial 50 subjects.
# Statistical Methods of Analysis
$$H_0: P_{\text{DISSECTION}} \geq P_{PG} = 25\%$$
$$H_A: P_{\text{DISSECTION}} < P_{PG} = 25\%$$
$P_{\text{DISSECTION}} = 30$-day mortality rate in targeted population
$P_{PG} =$ Performance Goal (PG) for 30-day mortality rate.
Expected 30-day mortality rate = 11%
1-sided alpha error ($\alpha$) = 5%
Power of the test = 80%
Sample size (n): 50 subjects
The primary endpoint was analyzed using the exact test method based on a binomial distribution. The null hypothesis will be rejected if the upper limit of the one-sided 95% confidence interval on the 30-day mortality rate is less than 25%. The one-sided upper 95% confidence interval on the 30-day mortality rate will be calculated based on a binomial distribution.
Additionally, separate secondary analyses were performed for all-cause mortality within 30 days for the groups of subjects with the two complicating factors of rupture and ischemia. Secondary endpoints are presented descriptively.
The Performance Goal was set at 25% after considering the mortality rates from 1) the Society for Vascular Surgery (SVS) Master Access File (MAF) of 85 acute, complicated dissection subjects; 2) the recent literature on open surgical repair and 3) the recent literature on TEVAR treated dissection patients. The performance goal allowed for reasonable variances due to the low rate of occurrence, the low baseline sample size in the literature and MAF and for variances in outcomes due to both a potential difference in patient complicating factors and a broader selection of physicians implanting the device in this study.
The primary endpoint analysis set included all enrolled subjects who had at least one (1) study stent graft implanted. The Intent-to-Treat (ITT) analysis set included all enrolled subjects who had an intra-arterial access procedure with intent to receive the study device.
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All 50 subjects enrolled in the study received the study stent graft and therefore the two (2) analysis sets defined above are identical. The primary endpoint and secondary observations were analyzed with all 50 ITT subjects.
## External Evaluation Groups
There were three external evaluation groups that independently reviewed data for this study. These groups were a Clinical Events Committee (CEC), a Data Monitoring Committee (DMC) and an imaging core laboratory.
### Clinical Events Committee (CEC)
The CEC was a group of physicians, independent of the clinical study with expertise and experience in the endovascular repair of descending thoracic aortic pathologies. The CEC met to review and adjudicate all deaths and UADEs for relatedness to the aorta, device and procedure. There were no UADEs identified in this study.
### Data Monitoring Committee (DMC)
The DMC was composed of at least five members, including four physicians from the fields of vascular surgery, cardiothoracic surgery, interventional radiology or interventional cardiology and one biostatistician, none of whom were involved in the conduct of the study. The DMC reviewed the 30-day data for the first 20 subjects and for the first 30 subjects. The committee recommended that the clinical trial could continue without modifications.
### Core Laboratory (Core Lab)
In order to provide independent verification of imaging findings, images required by protocol were sent by the sites to a central imaging core lab. Medical Image & Data Management Services Inc. (M2S) served as the independent image core lab for this study. Investigational sites submitted contrast-enhanced/non-contrast computerized tomography (CT) or contrast-enhanced magnetic resonance (MR) imaging to the core lab for three-dimensional reconstructions. Three-dimensional reconstruction was undertaken in order to provide critical and comprehensive data evaluation during the pre- and post-operative periods. Chest x-rays were also submitted to the core lab for analysis. M2S technology processes and systems are GMP/GCP, HIPAA, and CFR 21 Part 11 compliant and are provided within an ISO 13485 certified facility which adheres to all applicable federal regulations.
### 1. Clinical Inclusion and Exclusion Criteria
The study investigators were responsible for ensuring the subjects met the inclusion and exclusion criteria for the trial. Pre-treatment evaluation included a CTA/MRA for assessment of the aortic morphology and vascular characteristics. A physical exam was conducted and medical history and the inclusion/exclusion criteria below were assessed.
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Enrollment in the Medtronic Dissection Trial was limited to patients who met the following inclusion criteria:
- Subject signed an informed consent.
- Subject is at least 18 years old.
- Subject has an acute, complicated Type B aortic dissection with evidence of at least one of the following:
o Malperfusion (visceral, renal, spinal cord and/or lower limb ischemia)
▪ Visceral ischemia measured by either radiographic or clinical evidence.
▪ Renal ischemia measured by either radiographic or clinical evidence.
▪ Spinal cord ischemia measured by either radiographic or clinical evidence.
▪ Lower limb ischemia measured by either radiographic or clinical evidence.
o Rupture – Measured by radiographic or clinical evidence.
o Rupture – Measured by radiographic or clinical evidence.
- Subject is hemodynamically stable.
- Subject's anatomy must meet all of the following anatomical criteria:
o Proximal landing zone aortic diameter must be between 20 mm and 44 mm;
o Centerline distance from distal margin of left CCA or in cases of bovine anatomy, innominate artery, to start of most proximal tear must be ≥ 20 mm;
o Subject has patent iliac or femoral arteries or can tolerate an iliac conduit that allows endovascular access to the dissection site with the delivery system of the appropriate sized device.
- Thoracic aortic dissection is confirmed, at a minimum, by diagnostic contrast-enhanced computerized tomography angiogram (CTA) with 3-D reconstruction, and/or contrast enhanced magnetic resonance angiogram (MRA) obtained prior to the implant procedure.
Patients were not permitted to enroll in the Medtronic Dissection Trial if they met any of the following exclusion criteria:
- Planned placement of the covered portion of the stent graft over the left carotid artery, or the celiac trunk.
- Subject has systemic infection.
- Subject is pregnant.
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- Subject has received a previous stent or stent graft or previous surgical repair in the DTA.
- Subject has had a cerebral vascular accident (CVA) within 2 months.
- Subject has a history of bleeding diathesis, coagulopathy, or refuses blood transfusion.
- Subject has a history of Marfan Syndrome or other connective tissue disorder.
- Subject is currently participating in an investigational drug or device clinical trial which would interfere with the endpoints and follow-ups of this study.
- Subject has a known allergy or intolerance to the device components.
- Subject has a known hypersensitivity or contraindication to anticoagulants or contrast media, which is not amenable to pre-treatment.
- Subject has a co-morbidity causing expected survival to be less than 1 year.
# 2. Follow-up Schedule
In addition to pre-treatment evaluations, data was collected during the procedure, post-operatively and at hospital discharge. After discharge, subjects were required to comply with follow-up visits and evaluations that occur at one, six, and 12 months and annually for five years post-implant. At each follow-up, a physical exam, CT with and without contrast, or an MRA and x-ray were performed per the protocol schedule.
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**Table 3. Overview of the study procedures and data collection requirements**
| Data | Screening / Baseline | Procedure | Pre-Hospital Discharge | 1-month FU ± 14 days | 6-Month FU ± 60 days | 12-Month FU ± 90 days | 2 - 5 Year FU ± 16 weeks |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Informed Consent | ✓ | | | | | | |
| Vital Signs, ABI, Pulse | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ |
| Pregnancy test (if applicable) | ✓ | | | | | | |
| Medical History | ✓ | | | | | | |
| Device & Procedure Information | | ✓ | | | | | |
| Angiogram | | ✓ | | | | | |
| Laboratory Tests Serum Creatinine, GFR | ✓ | | | | | | |
| CT w/out contrast & CTA/MRA | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ |
| Chest X-Ray | | | | ✓ | ✓ | ✓ | ✓ |
| Adverse Event Assessment | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
### 3. Clinical Endpoints
The primary hypothesis of the study was that all-cause mortality through 30 days post-treatment met the performance goal of 25%. The performance goal was justified based on historical data, including the Society for Vascular Surgery (SVS) Master Access File (MAF) of 85 acute, complicated dissection subjects and the open surgical repair and endovascular repair literature.
Additional secondary objectives evaluated the safety and effectiveness by reporting the following outcomes:
Acute Observations (to 30 days)
- Successful delivery and deployment of the stent graft
- Coverage of proximal entry tear
- Aortic remodeling
- Serious Adverse Events (SAE)
- Rupture
Late Observations
- Aortic remodeling at 6 and 12 month visit
- Secondary procedures within 12 months
- Continuing or new false lumen (FL) perfusion
- SAEs within 12 months
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- Rupture within 12 months
- All-cause mortality within 12 months
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.
With regard to success/failure criteria, the overall Medtronic Dissection Trial 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
Fifty subjects (50) were enrolled in this study between June 2010 and May 2012, at 16 investigational sites. All enrolled subjects underwent endovascular repair with the Valiant Captivia to treat acute complicated Type B aortic dissection. Subjects enrolled in the Medtronic Dissection Trial were required to return for follow-up visits as described in Table 3.
A total of 89 subjects were screened for enrollment in the study. The reasons for exclusion were lack of malperfusion or rupture (n=10), presence of chronic dissection >14 days (n=7), inability to consent (n=3), no indication for intervention (n=3), inclusion criteria not met (n=2), fenestrated (n=2), intramural hematoma without dissection (n=2), <20 mm proximal landing zone (n=2), unreliable for follow-up (n=1), patient refused (n=1), previous repair (n=1), medically managed (n=1), history of aortic repair (n=1), unstable for surgery (n=1), Marfan's Syndrome (n=1), and retrograde extension to LCC (n=1).
Four (4) subjects died within 30 days of the index procedure. Of the 46 subjects eligible for 1-month follow-up, the clinical and imaging compliance was 97.8%. One (1) subject voluntarily withdrew from the study between the 1-month and 6-month visit. One (1) subject was lost to follow-up after the 1-month visit.
In the interval between 1 month and 6 months post-procedure, three (3) additional subjects died. During the same period, one (1) subject was lost to follow up and one (1) subject withdrew from the study. Of the 41 subjects eligible for the 6-month follow-up visit, 36 subjects completed the clinical follow-up visit and 34 subjects completed the imaging, resulting in a compliance of 87.8% and 82.9% respectively.
One subject died on day 432 post-procedure, within the 12-month visit window. However, because the subject died after the statistical analysis window of 365 days; this subject death is not counted in the 12-month mortality tables. There were 40 subjects eligible for the 12-month follow-up visit. The clinical and imaging
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compliance at this follow-up visit were 90.0% and 85% respectively. There were no subjects lost to follow-up, withdrawals or conversion to open surgery between the 6 month and the 1 year interval.
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Table 4. Subject Follow up, Imaging and Accountability
| | Subject Follow-up % (m/n)^{2} | | | Subject Imaging % (m/n)^{2} | | | Subjects with Adequate Imaging to Assess the Parameter % (m/n)^{2} | | | | | Subject Events Occurring Before Next Visit | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Implant and Follow-up | Eligible^{1} | Clinical Follow-up | Imaging Follow-up | CT/MR Imaging | Chest X-Ray | Additional Imaging Modalities | Max DTA Diameter | Change in Max DTA Diameter from Discharge^{3} | Endoleak | Migration | Integrity | Enrolled but not Implanted | Withdrawal | Conversion to Surgery | Death | Lost to Follow-up | Not Due for Next Visit |
| Implant | 50 | | | | | | | | | | | | | | | | |
| Events Between Implant and Discharge | | | | | | | | | | | | 0 | 0 | 0 | 3 | 0 | 0 |
| Discharge | 47 | 97.9% (46/47) | 80.9% (38/47) | 76.6% (36/47)^{4} | | 2.1% (1/47) | 76.6% (36/47) | | 68.1% (32/47) | | 78.7% (37/47) | | | | | | |
| Events Between Discharge and 1-Month | | | | | | | | | | | | | 0 | 0 | 1 | 0 | 0 |
| 1-Month | 46 | 97.8% (45/46) | 97.8% (45/46) | 97.8% (45/46) | 91.3% (42/46) | 0.0% (0/46) | 95.7% (44/46) | | 87.0% (40/46) | 97.8% (45/46) | 95.7% (44/46) | | | | | | |
| Events Between 1-Month and 6-Month | | | | | | | | | | | | | 1 | 0 | 3 | 1 | 0 |
| 6-Month | 41 | 87.8% (36/41) | 82.9% (34/41) | 80.5% (33/41) | 68.3% (28/41) | 0.0% (0/41) | 80.5% (33/41) | 80.5% (33/41) | 78.0% (32/41) | 78.0% (32/41) | 78.0% (32/41) | | | | | | |
| Events Between 6-Month and 12-Month | | | | | | | | | | | | | 0 | 0 | 1 | 0 | 0 |
| 12-Month | 40 | 90.0% (36/40) | 85.0% (34/40) | 85.0% (34/40) | 75.0% (30/40) | 0.0% (0/40) | 85.0% (34/40) | 85.0% (34/40) | 85.0% (34/40) | 85.0% (34/40) | 85.0% (34/40) | | | | | | |
| Total | 0 | 1 | 0 | 8 | 1 |
| --- | --- | --- | --- | --- | --- |
| Deaths Post Conversion to Surgery | | | 0 | | |
| Total Deaths | | | 8 | | |
$^{1}$ Eligible at implant are all subjects enrolled by snapshot date. Eligible (E$_{T}$) for time intervals post implant is eligible from the previous interval (E$_{T}$) less the sum of enrolled but not implanted (ENI) plus withdrawal (W) plus conversion to surgery (CTS) plus death (D) plus lost to follow up (LTF) plus not due for next visit (NDNV) subjects. E$_{T}$ = E$_{T}$ - (ENI + W + CTS + D + LTF + NDNV)
$^{2}$ Percentages for eligible subjects are based on number of all subjects enrolled by snapshot date and for clinical and site reported imaging follow-up are based on number of subjects who had follow-up visit within window divided by number of eligible subjects. Within window visits are defined as: for discharge: day 0 to the day of discharge, for 1 month: 16-44 days, for 6 months: 123-243 days, for 12 months: 275-455 days, for 2 years: 619-843 days, for 3 years: 984-1208 days, for 4 years: 1349-1573 days, for 5 years: 1714-1938 days.
$^{3}$ The first post-implant image will be used as the baseline image for measuring the change in DTA diameter and migration.
$^{4}$ 36 subjects had CTs and 2 subjects had X-ray imaging only. X-ray imaging was not required at pre-discharge and thus these two patients do not show up under the X-ray column.
m = number of subjects in category, n = number of subjects with available values
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### C. Study Population Demographics and Baseline Parameters
Baseline parameters of the study subjects included demographics, medical history, American Society of Anesthesiologists (ASA) Physical Status Classification and initial dissection assessment via imaging at presentation.
Because data on subjects with acute complicated type B dissections in the SVS MAF was used to calculate the PG, a comparison of the SVS MAF and Medtronic Dissection Trial subjects has been provided in the results tables where data was available.
#### Demographics
**Table 5** below presents comparative demographic data between the SVS MAF subjects and the Medtronic Dissection Trial subjects. The mean subject age was approximately $57.2 \pm 12.9$ years in the Dissection subjects and $58.3 \pm 15.4$ years in the SVS MAF subjects. Dissection subjects were predominantly male (80%) and Caucasian (62%), with African American (22%), Asian (12%) and other races (4%) represented. The SVS MAF subjects were also predominantly male (72.9%) and Caucasian (52.9%), with African American (27.1%), Asian (3.5%) and other races (2.4%) represented. While the data on the subject's race was available on all the 50 Dissection subjects, the data was unavailable on 14.1% of the SVS MAF subjects.
| Subject Demographic | SVS MAF Subjects | Dissection Subjects^{1} |
| --- | --- | --- |
| **Age (years)** | | |
| n | 85 | 50 |
| Mean ± SD | 58.3 ± 15.4 | 57.2 ± 12.9 |
| Median | 59.0 | 56.5 |
| Min, Max | 25, 88 | 18, 83 |
| **Sex % (m/n)** | | |
| Male | 72.9% (62/85) | 80.0% (40/50) |
| Female | 27.1% (23/85) | 20.0% (10/50) |
| **Ethnicity % (m/n)** | | |
| Hispanic or Latino | 14.3% (12/84) | 10.0% (5/50) |
| Not Hispanic or Latino | 85.7% (72/84) | 88.0% (44/50) |
| Not Available | -- | 2.0% (1/50) |
| Refuses to answer | NA | -- |
| **Race % (m/n)** | | |
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Table 5. Subject Demographics
| Subject Demographic | SVS MAF Subjects | Dissection Subjects^{1} |
| --- | --- | --- |
| Caucasian | 52.9% (45/85) | 62.0% (31/50) |
| Black or African American | 27.1% (23/85) | 22.0% (11/50) |
| Asian | 3.5% (3/85) | 12.0% (6/50) |
| Native Hawaiian or Other Pacific Islander | 1.2% (1/85) | -- |
| American Indian or Alaskan Native | 1.2% (1/85) | -- |
| Other | -- | 4.0% (2/50) |
| Not Available | 14.1% (12/85) | -- |
$^{1}$Based on number of ITT subjects with available data. ITT subjects are all enrolled subjects.
m = number of subjects in category, n = number of subjects with available values
### Medical History
Table 6 summarizes the medical history of the subjects with available data. Among the Medtronic Dissection Trial subjects, conditions that are common to cardiovascular disease are represented; specifically, hypertension (90.0%), current tobacco use (43.8%), hyperlipidemia (32.7%), peripheral vascular disease (14.0%), coronary artery disease (12.0%), abdominal aortic aneurysm (12.0%) and ascending thoracic aneurysm (8.0%).
Similar to the Medtronic Dissection Trial subjects, the SVS MAF subjects had a high incidence of hypertension (83.5%) and current tobacco use (32.5%). Information among other categories such as hyperlipidemia, peripheral vascular disease, coronary artery disease, abdominal aortic aneurysm and ascending thoracic aneurysm was unavailable for the SVS MAF subjects.
Among the SVS MAF subjects, 11.8% had vascular disorders as compared to 44% in the Medtronic Dissection Trial group and 7.1% of the SVS MAF subjects had GU/Renal disorders, as compared to 38% in the Medtronic Dissection Trial group.
Table 6. Subject Medical History
| Subject Medical History | SVS MAF Subjects % (m/n) | Dissection Subjects % (m/n)^{1} | p-value^{2} |
| --- | --- | --- | --- |
| Cardiac | 89.4% (76/85) | 90.0% (45/50) | >0.999 |
| Congestive Heart Failure | 10.6% (9/85) | 8.0% (4/50) | 0.767 |
| Hypertension | 83.5% (71/85) | 90.0% (45/50) | 0.443 |
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Table 6. Subject Medical History
| Subject Medical History | SVS MAF Subjects % (m/n) | Dissection Subjects % (m/n)^{1} | p-value^{2} |
| --- | --- | --- | --- |
| MI | 11.8% (10/85) | 6.0% (3/50) | 0.371 |
| Arrhythmia | 11.8% (10/85) | 8.0% (4/50) | 0.571 |
| Angina | NA | 14.0% (7/50) | NA |
| Coronary Artery Disease | NA | 12.0% (6/50) | NA |
| Coronary Artery Bypass Grafting (CABG) | NA | 2.0% (1/50) | NA |
| Percutaneous Coronary Intervention | NA | 4.0% (2/50) | NA |
| Other Cardiac | NA | 4.0% (2/50) | NA |
| **Vascular** | 11.8% (10/85) | 44.0% (22/50) | <0.001 |
| Abdominal Aortic Aneurysm | NA | 12.0% (6/50) | NA |
| Ascending Thoracic Aneurysm | NA | 8.0% (4/50) | NA |
| Family History of Aneurysms | NA | 4.3% (2/47)^{2} | NA |
| Peripheral Vascular Disease | NA | 14.0% (7/50) | NA |
| Carotid Artery Disease | NA | 4.1% (2/49)^{2} | NA |
| Lower Extremity Claudication | NA | 6.1% (3/49)^{2} | NA |
| Lower Extremity Rest Pain | NA | 6.0% (3/50) | NA |
| Lower Extremity Ulcers | NA | 4.0% (2/50) | NA |
| DVT | NA | 6.0% (3/50) | NA |
| Pulmonary Embolus | NA | -- | NA |
| Other Vascular | NA | 14.0% (7/50) | NA |
| **Pulmonary** | 12.9% (11/85) | 18.0% (9/50) | 0.458 |
| COPD | 10.6% (9/85) | 4.0% (2/50) | 0.212 |
| Mechanical Ventilation (for > 24 hrs) | NA | 6.0% (3/50) | NA |
| Other Chronic Pulmonary Disease | 2.4% (2/85) | 12.0% (6/50) | 0.051 |
| **Cerebrovascular/Neurological** | 7.1% (6/85) | 8.0% (4/50) | >0.999 |
| Transient Ischemic Attack (TIA) | -- | -- | NA |
| Stroke/Cerebrovascular Accident (CVA) | 3.5% (3/85) | 4.0% (2/50) | >0.999 |
| Paraplegia | 2.4% (2/85) | -- | 0.530 |
| Paraparesis | 1.2% (1/85) | 2.0% (1/50) | >0.999 |
| Other Cerebrovascular/Neurological | -- | 2.0% (1/50) | 0.370 |
| **GU/Renal** | 7.1% (6/85) | 38.0% (19/50) | <0.001 |
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Table 6. Subject Medical History
| Subject Medical History | SVS MAF Subjects % (m/n) | Dissection Subjects % (m/n)^{1} | p-value^{2} |
| --- | --- | --- | --- |
| Hemodialysis | NA | 2.0% (1/50) | NA |
| Chronic Renal Failure | NA | -- | NA |
| Renal Insufficiency | NA | 24.0% (12/50) | NA |
| Other GU/Renal | NA | 16.0% (8/50) | NA |
| **Connective Tissue Disease** | 4.7% (4/85) | -- | 0.296 |
| Marfan Syndrome | NA | -- | NA |
| Ehlers Danlos | NA | -- | NA |
| Other Connective Tissue Disease | NA | -- | NA |
| **Diabetes Mellitus** | 12.9% (11/85) | 8.0% (4/50) | 0.572 |
| Insulin Dependent | NA | 2.0% (1/50) | NA |
| **Cancer** | 9.4% (8/85) | 14.0% (7/50) | 0.412 |
| **Liver Disease** | -- | -- | NA |
| **GI Conditions** | NA | 22.4% (11/49)^{2} | NA |
| **Bleeding Disorder** | NA | --^{2} | NA |
| **Hyperlipidemia** | NA | 32.7% (16/49)^{2} | NA |
| **Other Systemic Conditions** | NA | 4.1% (2/49)^{2} | NA |
| **History of EtOH Abuse** | NA | 4.0% (2/50) | NA |
| **Tobacco Use** | | | 0.355 |
| Current Smoker | 32.5% (27/83) | 43.8% (21/48)^{2} | |
| Former Smoker | 37.3% (31/83) | 35.4% (17/48)^{2} | |
| Never Smoked | 30.1% (25/83) | 20.8% (10/48)^{2} | |
| **Other Medical History** | NA | 40.0% (20/50) | NA |
$^{1}$Based on number of ITT subjects with available data
$^{2}$Not all subjects answered every medical history question and that is reflected in the denominator for each category. In cases where the data was missing, the sites were queried and the data was unavailable.
m = number of subjects in category, n = number of subjects with available values. A subject may have more than one condition; hence, number of subjects at higher level may not be equal to the total at lower level.
$^{3}$Fisher's exact test
### Clinical Symptoms
A summary of the clinical symptoms that the subjects reported at onset and at presentation are summarized in Table 7. The most common symptoms for the Medtronic Dissection Trial subjects at onset were back/chest pain (88.0%),
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hypertension (52.0%), abdominal pain (36.0%), nausea/vomiting (24.0%) and paraparesis (12.0%). There were minimal differences between the clinical symptoms of the subjects at onset and presentation. Of the 50 subjects enrolled in the study
- 40 subjects (80%) experienced malperfusion with no rupture,
- 7 subjects (14%) experienced rupture with no malperfusion and
- 3 subjects (6%) experienced both malperfusion and rupture
The most common symptoms for the SVS MAF subjects at onset were pain (76.5%), hypertension (43.5%) and bleeding (8.2%).
Table 7. Clinical Symptoms
| | SVS MAF Subjects | Dissection Subjects^{1} | p-value^{2} |
| --- | --- | --- | --- |
| Rupture % (m/n) | 31.8% (27/85) | 20.0% (10/50) | 0.165 |
| Malperfusion % (m/n) | 71.8% (61/85) | 86.0% (43/50) | 0.089 |
| Visceral Ischemia % (m/n) | 14.1% (12/85) | 40.0% (20/50) | 0.001 |
| Renal Ischemia % (m/n) | 25.9% (22/85) | 42.0% (21/50) | 0.058 |
| Lower Limb Ischemia % (m/n) | 40.0% (34/85) | 40.0% (20/50) | >0.999 |
| Spinal Cord Ischemia % (m/n) | 2.4% (2/85) | 6.0% (3/50) | 0.359 |
| Ischemia (Other) % (m/n) | 5.9% (5/85) | 2.0% (1/50) | 0.412 |
| At Onset | | | |
| Duration from Onset to Presentation (days) | | | |
| n | NA | 50 | |
| Mean ± SD | NA | 1.4 ± 2.4 | NA |
| Median | NA | 0.0 | |
| Min, Max | NA | 0, 10 | |
| Duration from Onset to Procedure (days) | | | |
| n | 85 | 50 | |
| Mean ± SD | 2.9 ± 3.4 | 4.7 ± 4.5 | 0.015 |
| Median | 1.0 | 3.0 | |
| Min, Max | 0, 14 | 0, 23 | |
| Hypertension % (m/n) | 43.5% (37/85) | 52.0% (26/50) | 0.375 |
| Pain % (m/n) | 76.5% (65/85) | 94.0% (47/50) | 0.009 |
| Abdominal Pain % (m/n) | NA | 36.0% (18/50) | NA |
| Back/Chest Pain % (m/n) | NA | 88.0% (44/50) | NA |
| Bleeding % (m/n) | 8.2% (7/85) | 2.0% (1/50) | 0.257 |
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Table 7. Clinical Symptoms
| | SVS MAF Subjects | Dissection Subjects^{1} | p-value^{2} |
| --- | --- | --- | --- |
| Paraplegia % (m/n) | NA | 4.0% (2/50) | NA |
| Paraparesis % (m/n) | NA | 12.0% (6/50) | NA |
| Headache % (m/n) | NA | 4.0% (2/50) | NA |
| Syncope/Altered Consciousness % (m/n) | NA | -- | NA |
| Nausea/Vomiting % (m/n) | NA | 24.0% (12/50) | NA |
| At Presentation | | | |
| Duration from Presentation to Procedure (days) | | | |
| n | NA | 50 | |
| Mean ± SD | NA | 3.3 ± 3.6 | NA |
| Median | NA | 1.5 | |
| Min, Max | NA | 0, 14 | |
| Hypertension % (m/n) | NA | 60.0% (30/50) | NA |
| Pain % (m/n) | NA | 92.0% (46/50) | NA |
| Abdominal Pain % (m/n) | NA | 42.0% (21/50) | NA |
| Back/Chest Pain % (m/n) | NA | 78.0% (39/50) | NA |
| Bleeding % (m/n) | NA | 2.0% (1/50) | NA |
| Paraplegia % (m/n) | NA | 4.0% (2/50) | NA |
| Paraparesis % (m/n) | NA | 14.0% (7/50) | NA |
| Headache % (m/n) | NA | 4.0% (2/50) | NA |
| Syncope/Altered Consciousness % (m/n) | NA | 2.0% (1/50) | NA |
| Nausea/Vomiting % (m/n) | NA | 18.0% (9/50) | NA |
| New Medications After Admission | | | |
| Inotropic Support % (m/n) | NA | 16.0% (8/50) | NA |
| Anti-Hypertensives % (m/n) | NA | 84.0% (42/50) | NA |
$^{1}$Based on number of ITT subjects with available data
m = number of subjects in category, n = number of subjects with available values
$^{2}$A t-test was performed on duration measures; Fisher's exact test was carried out on other parameters.
### Initial Dissection Assessment
The initial dissection assessment information is summarized in Table 8. Dissection originated at the LSA in 37 (74%) of the subjects and at greater than 2 cm distal to the
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LSA in 11(22%) of the 50 subjects. The extent of the initial dissection was available on 49 of the 50 subjects. In only three (3) cases (6.1%) was the dissection limited to the thoracic aorta. Thirty five (71.4%) of the 49 subjects had a dissection that extended to or past the aortic bifurcation into the iliac or femoral arteries.
The proximal entry tear was located in the proximal descending aorta in the majority (90%) of the subjects, in the mid descending aorta in 6% and in the distal descending aorta in 4% of the subjects. There were no visible re-entry tears in 24 of the 50 subjects.
**Table 8. Initial Dissection Assessment**
| Initial Dissection Assessment | % (m/n)^{1} |
| --- | --- |
| **Site of Proximal Entry Tear** | |
| Proximal Descending Aorta | 90.0% (45/50) |
| Mid Descending Aorta | 6.0% (3/50) |
| Distal Descending Aorta | 4.0% (2/50) |
| **Visible Re-entry Tears** | |
| None | 48.0% (24/50) |
| One Tear | 10.0% (5/50) |
| Two Tears | 14.0% (7/50) |
| Three Tears | 8.0% (4/50) |
| Four Tears | 14.0% (7/50) |
| Five Tears | 6.0% (3/50) |
| **Most Proximal Aspect of Dissection** | |
| At LSA | 74.0% (37/50) |
| Greater Than 2 cm Distal to LSA | 22.0% (11/50) |
| Mid Descending Aorta | 4.0% (2/50) |
| **Most Distal Aspect of Dissection** | |
| Thoracic Aorta | 6.1% (3/49) |
| Celiac Trunk | 2.0% (1/49) |
| Superior Mesenteric Artery | -- |
| Abdominal Aorta (Suprarenal) | -- |
| Abdominal Aorta (Infrarenal) | 20.4% (10/49) |
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Table 8. Initial Dissection Assessment
| Initial Dissection Assessment | % (m/n)^{1} |
| --- | --- |
| Aortic Bifurcation | 6.1% (3/49) |
| Common Iliac | 28.6% (14/49) |
| Internal Iliac | 4.1% (2/49) |
| External Iliac | 20.4% (10/49) |
| Femoral Artery | 12.2% (6/49) |
$^{1}$Based on number of ITT subjects with available data
m = number of subjects in category, n = number of subjects with available data
### ASA Physical Classification
Based on the medical history and physical condition, the subjects were stratified into four (4) different classes according to the American Society of Anesthesiologists (ASA) Physical Status Classification System as reported in Table 9. The majority of the Medtronic Dissection Trial subjects and the SVS MAF subjects were Class III with severe systemic disease or Class IV with severe systemic disease that was a constant threat to life. The distribution of subjects across the different ASA Physical Status classifications was similar in the Dissection and the SVS MAF groups.
Table 9. ASA Physical Classification
| ASA Physical Classification | SVS MAF Subjects % (m/n) | Dissection Subjects % (m/n)^{1} |
| --- | --- | --- |
| I | -- | -- |
| II | 2.4% (2/85) | 6.0% (3/50) |
| III | 22.4% (19/85) | 22.0% (11/50) |
| IV | 64.7% (55/85) | 66.0% (33/50) |
| V | 10.6% (9/85) | 6.0% (3/50) |
| Not assessed | -- | -- |
$^{1}$Based on number of ITT subjects with available data
m = number of subjects in category, n = number of subjects with available values
### Dissection Characteristics
Pre-procedural imaging was used to measure the vessel dimensions. In many cases
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when CT imaging was insufficient, both angiography and IVUS were used for initial measurements by the sites.
The baseline vessel diameters are presented in Table 10 below. The protocol required the proximal landing zone aortic diameter to be between 20 mm and 44 mm.
| Table 10. Aortic and Iliac Measurements at Presentation: Diameters | |
| --- | --- |
| Thoracic Aortic Measurements: Diameters (mm)^{1} | Site Reported |
| **AD1: Maximum Thoracic Aortic Centerline Diameter** | |
| N | 50 |
| Mean ± SD | 40.6 ± 7.5 |
| Median | 40.0 |
| Min, Max | 18, 60 |
| **AD2: Maximum True Lumen Diameter at AD1** | |
| N | 50 |
| Mean ± SD | 19.9 ± 9.9 |
| Median | 20.0 |
| Min, Max | 3, 52 |
| **AD3: Maximum False Lumen Diameter at AD1** | |
| N | 50 |
| Mean ± SD | 23.0 ± 8.9 |
| Median | 23.5 |
| Min, Max | 0, 40 |
| **D1: Diameter of Distal Margin of L CCA (Long Axis of Ellipse)** | |
| N | 50 |
| Mean ± SD | 32.0 ± 4.3 |
| Median | 32.0 |
| Min, Max | 20, 44 |
| **Diameter at Proximal Landing Zone if Different from D1** | |
| N | 50 |
| Mean ± SD | 31.4 ± 3.1 |
| Median | 31.0 |
| Min, Max | 22, 38 |
| **Right External Iliac Artery Diameter** | |
| N | 49 |
| Mean ± SD | 10.2 ± 2.6 |
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| Table 10. Aortic and Iliac Measurements at Presentation: Diameters | |
| --- | --- |
| Thoracic Aortic Measurements: Diameters (mm)^{1} | Site Reported |
| Median | 10.0 |
| Min, Max | 5, 18 |
| Left External Iliac Artery Diameter | |
| N | 49 |
| Mean ± SD | 10.0 ± 3.0 |
| Median | 10.0 |
| Min, Max | 0, 18 |
| ^{1}Based on number of ITT subjects with available data | |
The baseline vessel lengths are presented in Table 11 below. The protocol required that the centerline distance from distal margin of left CCA or in cases of bovine anatomy, innominate artery, to the start of the most proximal tear must be greater than or equal to 20 mm. All of the enrolled subjects met this inclusion criterion.
| Table 11. Aortic Measurements at Presentation: Lengths | |
| --- | --- |
| Thoracic Aortic Measurements: Lengths (mm)^{1} | Site Reported |
| L1: Landing Zone (Distal Margin of LCCA to Primary Entry Tear) | |
| N | 50 |
| Mean ± SD | 39.7 ± 34.0 |
| Median | 29.5 |
| Min, Max | 20, 223 |
| L2: Total Length of Aortic Dissection (Thoracic and Abdominal) | |
| N | 46 |
| Mean ± SD | 376.4 ± 111.4 |
| Median | 378.0 |
| Min, Max | 50, 580 |
| L3: Total Thoracic Aortic Length (L CCA to Celiac) | |
| N | 47 |
| Mean ± SD | 278.4 ± 63.6 |
| Median | 271.0 |
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Table 11. Aortic Measurements at Presentation: Lengths
| Thoracic Aortic Measurements: Lengths (mm)^{1} | Site Reported |
| --- | --- |
| Min, Max | 190, 580 |
| ^{1}Based on number of ITT subjects with available data | |
### Summary of Study Population Demographics and Baseline Parameters
In summary, the subjects treated in the Medtronic Dissection Trial presented with a complicated morbid disease. They were characterized by demographics, medical history and clinical symptoms and were compared to subjects in the SVS MAF group, where data was available. Subject demographics, history and symptoms were comparable between the two study groups, although it appeared that the Medtronic Dissection Trial subjects' history showed more extensive systemic disease.
### Acute Procedural Data
The technical success was 100% in this study as shown in Table 12. The device was successfully delivered and deployed and the proximal entry tear was successfully covered in all subjects.
As summarized in Table 13, the most proximal device was implanted in either Zone 2 or Zone 3 in 46 of the 50 subjects. In three (3) subjects, the proximal device was placed in Zone 4 and in one (1) subject, the proximal device was placed in Zone 1. One (1) subject had a bovine arch with a common takeoff of the innominate & LCA. The stent graft was deployed with the covered portion at the distal margin of the common trunk covering the LSA.
Table 12. Technical Success
| Technical Success^{1} | % (m/n) |
| --- | --- |
| Vessel Access Success | 100.0% (50/50) |
| Delivery Success | 100.0% (50/50) |
| Deployment Success | 100.0% (50/50) |
| ^{1}Based on number of ITT subjects with available data m = number of subjects in category, n = number of subjects with available values | |
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Table 13. Implanted Zone at Initial Procedure
| Implanted Zone of Proximal Stent Graft | % (m/n)^{1} |
| --- | --- |
| Zone 1 | 2.0% (1/50) |
| Zone 2 | 58.0% (29/50) |
| Zone 3 | 34.0% (17/50) |
| Zone 4 | 6.0% (3/50) |
| ^{1}Based on number of implanted subjects with available data m = number of subjects in category, n = number of subjects with available data | |
Table 14. Entry Tear Coverage at Implant
| | % (m/n)^{1} |
| --- | --- |
| Proximal Entry Tear Covered | 100.0% (50/50) |
| ^{1}Based on number of ITT subjects with available data m = number of subjects with successful events, n = number of subjects with available values | |
### Stent Graft Usage and Oversizing
All subjects successfully received one (1) or more devices. There were no device malfunctions reported. Thirty one of the 50 subjects enrolled received a single device. Sixteen of the remaining subjects received two (2) stent grafts and three (3) subjects received three (3) stent grafts at the initial procedure.
Table 15 below contains the information regarding the average number of devices implanted per subject at initial procedure. Table 16 contains information regarding the types of devices implanted.
Table 15. Number of Devices Implanted at Initial Procedure
| Number of Devices Implanted | Subjects % (m/n)^{1} |
| --- | --- |
| 1 | 62.0% (31/50) |
| 2 | 32.0% (16/50) |
| 3 | 6.0% (3/50) |
| ^{1}Based on number of implanted subjects with available data m = number of subjects in category, n = number of subjects with available values | |
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Table 16. Devices Implanted by Type at Initial Procedure
| Device Type | % (m/n)^{1} |
| --- | --- |
| FreeFlo Straight (Proximal Component) | 75.0% (54/72) |
| Closed Web Straight (Distal Component) | 9.7% (7/72) |
| Distal Bare Spring Straight (Distal Component) | -- |
| Closed Web Tapered (Distal Component) | 15.3% (11/72) |
$^{1}$Based on total number of devices implanted in all subjects
m = number of devices in category, n = total number of devices implanted in all subjects
The Valiant Stent Graft was available in a wide set of sizes ranging from 22 mm to 46 mm in diameter, treating subjects with proximal landing zone diameter from 25 mm to 38 mm. The diameter of the majority of the devices implanted was between 32 mm and 40 mm. This data is summarized in Table 17 below.
Table 17. Proximal Diameters of Implanted Proximal Devices at Initial Procedure
| Device Diameter (mm)^{1} | Number of Devices Implanted (n) |
| --- | --- |
| 22 | 0 |
| 24 | 0 |
| 26 | 1 |
| 28 | 0 |
| 30 | 1 |
| 32 | 13 |
| 34 | 13 |
| 36 | 7 |
| 38 | 10 |
| 40 | 4 |
| 42 | 1 |
| 44 | 0 |
| 46 | 0 |
$^{1}$Based on number of implanted subjects with available data
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Table 18 provides the breakdown of the number of devices of different lengths that were used at the initial procedure. Forty six of the 72 devices implanted at the initial procedure were 150 mm in length.
| Table 18. Device Lengths at Initial Procedure | |
| --- | --- |
| Device Length (mm)^{1} | Number of Devices Implanted (n) |
| 100 | 4 |
| 150 | 46 |
| 200 | 22 |
| ^{1}Based on total number of devices implanted in all subjects | |
As reported by the core lab, the mean total length of coverage (reported in Table 19 below) after the procedure was 196.9 mm ± 67.1 mm ranging from 93 mm to 346 mm.
| Table 19. Core Lab Reported Length of Coverage at Baseline | |
| --- | --- |
| Length of Coverage at Baseline^{1,2} (mm) | |
| n | 47 |
| Mean ± SD | 196.9 ± 67.1 |
| Median | 170.9 |
| Min, Max | 93, 346 |
| ^{1}Baseline image is the first post-procedure image. ^{2}Based on number of implanted subjects with available data Core Lab Reported Table | |
Table 20 provides information on the device oversizing. The median oversizing for this population was 11.5 %. In one (1) subject, three (3) stent grafts were implanted in the descending thoracic aorta using the distal-to-proximal implantation technique. The diameter of the primary (most distal) device implanted was 34 mm. The first device placed proximal to the primary device was oversized by 2 mm and the second device placed proximal to the first device was further oversized by 2 mm per the IFU. This successive oversizing resulted in the most proximal piece having an oversizing measurement of 52%.
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Table 20. Device Oversizing at Initial Procedure
| Device Oversizing^{1} (%) | |
| --- | --- |
| n | 50 |
| Mean ± SD | 12.0 ± 10.3 |
| Median | 11.5 |
| Min, Max | -9, 52 |
$^{1}$Based on number of implanted subjects with available data
Device oversizing (%) = 100*(device diameter - diameter at proximal landing zone)/(diameter at proximal landing zone).
### Perioperative Data
All cases were performed under general anesthesia. Systemic heparin was administered in 98.0% of the subjects. Heparin was not administered in one (1) subject at the physician's discretion.
Cerebrospinal fluid (CSF) drainage and other spinal protective measures were used in 32.0% and 24.0% of the subject population respectively. No cases of spinal cord ischemia, paraplegia or paraparesis at the index procedure were reported.
The LSA was covered in 60.0% of the subjects (complete coverage: 44.0% and partial coverage: 16.0%).
Table 21. Implant Procedure
| Implant Procedure | % (m/n) |
| --- | --- |
| Heparin Administered During Implant | 98.0% (49/50) |
| Type of Anesthesia Used | |
| General | 100.0% (50/50) |
| Spinal | 4.0% (2/50) |
| Epidural | -- |
| Local | -- |
| Spinal Protective Measure | 54.0% (27/50) |
| Spinal CSF Drain | 32.0% (16/50) |
| Maintenance of controlled hypertension following placement | 6.0% (3/50) |
| Monitoring of evoked potentials | 18.0% (9/50) |
| LSA Coverage | |
| None | 40.0% (20/50) |
| Partial | 16.0% (8/50) |
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Table 21. Implant Procedure
| Implant Procedure | % (m/n) |
| --- | --- |
| Complete | 44.0% (22/50) |
| Subjects with LSA Coverage | |
| LSA Covered Subjects with Any Pre-implant Adjunctive Procedure^{1} | 10.0% (3/30) |
| LSA Covered Subjects with Any Post-implant Adjunctive Procedure^{2} | 23.3% (7/30) |
| m = number of subjects in category, n = number of subjects with available data. For Subjects with LSA Coverage, the denominator is based on those with LSA coverage or partial coverage. ^{1}These included carotid to subclavian bypass, left renal stent, left iliac stent, right iliac stent. ^{2}These included carotid to subclavian bypass, fem fem bypass, SMA stent, left iliac stent, right iliac stent and other. | |
The most commonly used access entry site was the femoral artery in 98.0% of the subjects. The brachial artery was used in 22.0% of the subjects for additional vascular access.
Table 22. Arterial Access Entry Site
| Arterial Access Entry Site | % (m/n)^{1} |
| --- | --- |
| Access Site Used to Deliver the Device | |
| Femoral Artery | 98.0% (49/50) |
| Iliac Artery | -- |
| Abdominal Aortic Conduit | -- |
| Iliac Conduit | 2.0% (1/50) |
| Additional Vascular Access Achieved Via | |
| Femoral Artery | 58.0% (29/50) |
| Iliac Artery | -- |
| Abdominal Aortic Conduit | -- |
| Iliac Conduit | -- |
| Brachial Artery | 22.0% (11/50) |
| Other | 8.0% (4/50)^{2} |
| NA | 12.0% (6/50) |
| ^{1}Based on number of ITT subjects with available data m = number of subjects in category, n = number of subjects with available values ^{2}All subjects had right radial artery access | |
The median duration of the implant procedure was reported as 108.5 minutes. One subject had a procedure time of 920 minutes. This subject had significant
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comorbidities and underwent several adjunct procedures. These factors contributed to the procedure lasting longer than usual.
Overall, the procedures required a median of 115.0 ml of contrast agent. The median reported blood loss during the procedure was 100.0 ml.
The duration of the overall hospital stay ranged from 1 to 124 days with a median of 9 days. Two (2) subjects experienced much longer times in the intensive care unit (ICU) and longer hospital stays than the other subjects enrolled. One of these subjects was in the ICU for 2,737 hours and hospitalized for 124 days. This subject was never discharged from the hospital and died secondary to cardiac arrest on post-operative day 124. The other subject was in the ICU for 1,040 hours and hospitalized for 72 days. This subject died secondary to pneumonia 87 days post-operatively. Time in intensive care was not reported for the subject who died during the implant procedure.
Additional measurements at implant are presented in the tables below.
Table 23. Acute Measurements at Implant
| Acute Measurements at Implant^{1} | |
| --- | --- |
| Duration of Implant Procedure (min) | |
| n | 50 |
| Mean ± SD | 142.9 ± 125.6 |
| Median | 108.5 |
| Min, Max | 45, 920 |
| Contrast Volume (ml) | |
| n | 47 |
| Mean ± SD | 122.2 ± 72.1 |
| Median | 115.0 |
| Min, Max | 20, 300 |
| Total Fluoroscopic Time (min) | |
| n | 42 |
| Mean ± SD | 17.1 ± 25.7 |
| Median | 12.2 |
| Min, Max | 4, 175 |
| Blood Loss During Procedure (ml) | |
| n | 49 |
| Mean ± SD | 180.1 ± 223.6 |
| Median | 100.0 |
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Table 23. Acute Measurements at Implant
| Acute Measurements at Implant^{1} | |
| --- | --- |
| Min, Max | 10, 1400 |
| Subjects Requiring Blood Transfusion % (m/n) | 40.0% (20/50) |
| Time in ICU (hours) | |
| n | 49 |
| Mean ± SD | 211.4 ± 429.2 |
| Median | 76.0 |
| Min, Max | 5, 2737 |
| Overall Hospital Stay (days) | |
| n | 50 |
| Mean ± SD | 14.1 ± 19.9 |
| Median | 9.0 |
| Min, Max | 1, 124 |
$^{1}$Based on number of ITT subjects with available data
m = number of subjects in category, n = number of subjects with available values
Table 24 lists the 7 (seven) adjunctive procedures performed prior to and twenty three (23) adjunctive procedures performed after deployment of the study device. Three (3) subjects had an LSA-Carotid bypass procedure before the implant and one (1) subject underwent the bypass as an adjunctive procedure after the implant.
Table 24. Adjunctive Procedures Performed
| Adjunctive Procedures Performed | Prior to Deployment % (m/n)^{1} | After Deployment % (m/n)^{2} |
| --- | --- | --- |
| Intervention location: Aortic arch | 6.0% (3/50) | 2.0% (1/50) |
| Carotid to Subclavian Bypass | 6.0% (3/50) | 2.0% (1/50) |
| Intervention location: Mesenteric vessels | -- | 2.0% (1/50) |
| SMA Stent | -- | 2.0% (1/50) |
| Intervention location: Renal vessels | 2.0% (1/50) | 2.0% (1/50) |
| Left Renal Stent | 2.0% (1/50) | -- |
| Right Renal Stent | -- | 2.0% (1/50) |
| Intervention location: Iliac vessels | 4.0% (2/50) | 16.0% (8/50) |
| Left Iliac Stent | 4.0% (2/50) | 12.0% (6/50) |
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Table 24. Adjunctive Procedures Performed
| Adjunctive Procedures Performed | Prior to Deployment % (m/n)^{1} | After Deployment % (m/n)^{2} |
| --- | --- | --- |
| Right Iliac Stent | 2.0% (1/50) | 8.0% (4/50) |
| Intervention location: Femoral vessels | -- | 6.0% (3/50) |
| Fem-Fem Bypass | -- | 6.0% (3/50) |
| Other (Listed in Error! Reference source not found. below) | -- | 14.0% (7/50) |
| No. of Subjects with Adjunctive Procedures^{4} | 6.0% (3/50) | 28.0% (14/50) |
$^{1}$Based on number of ITT subjects with available data
$^{2}$Based on number of implanted subjects with available data
m = number of subjects in category, n = number of subjects with available data
$^{4}$Some subjects had multiple adjunctive procedures.
A listing of the seven (7) other adjunctive procedures that were performed after deployment is included in Table 25.
Table 25. List of Other Adjunctive Procedures
| Other Adjunctive Procedures |
| --- |
| Thoracentesis/abd endoscopy |
| Thrombectomy left common/external IA, interposition graft L CFA |
| Laparotomy by General Surgery |
| Right common femoral exposure, false lumen thrombectomy and obliteration, patch angioplasty with bovi |
| Endovascular repair of abdominal aortic dissection |
| Right external iliac thrombectomy and stenting and fasciotomy of the right calf |
| Right axilla-femoral bypass and right sided calf fasciotomy |
### D. Safety and Effectiveness Results
#### 1. Safety Results
The primary endpoint analysis of all-cause mortality at 30 days was based on a cohort of 50 patients. Other safety outcomes are presented for 0 to 30 days post-implant procedure and 31 to 365 days post-implant procedure. The key safety outcomes for this study are presented below in Tables 26 to 37. Adverse events are reported in Tables 31 to 37.
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## Primary Endpoint Analysis
The primary endpoint for this trial was the all-cause mortality within 30 days of the index procedure. The Medtronic Dissection Trial met its primary endpoint with a 30-day all-cause mortality rate of 8.0%. The null hypothesis was rejected since the upper limit of the one-sided 95.0% confidence interval on the 30-day mortality rate was 17.4%, which was less than the performance goal of 25.0%. One (1) subject did not meet the inclusion criteria for an acute Type B aortic dissection. Table 34 shows the primary endpoint analysis on all enrolled subjects for all-cause mortality within 30 days. Table 35 shows the sensitivity analysis on the primary endpoint by excluding this subject from the ITT population. In either analysis (PP or ITT), the dissection trial met its primary endpoint.
Four (4) subjects died within 30 days of the study procedure.
- One subject died from cardiac tamponade on the day of the procedure
- One subject died from mesenteric ischemia in totalis on day 1 post-procedure
- One subject died from sepsis on day 9 post-procedure
- One subject died from a pulmonary embolism on day 26 post-procedure
Table 26. Primary Endpoint - All-Cause Mortality within 30 Days
| | % (m/n) [95% UCL]^{1, 2, 3} |
| --- | --- |
| 30-day All-Cause Mortality | 8.0% (4/50) [17.4%] |
| ^{1}95% Upper Confidence Limit (UCL) was calculated using an exact method based on the binomial distribution. ^{2}Based on the number of evaluable subjects. Subjects will be considered unevaluable if they are withdrawn before the lower limit of the 30-day follow-up window (16 days) or they are lost to follow-up before the lower limit of the 30-day follow-up window (16 days) and had no contact thereafter. ^{3}Based on CEC adjudicated data | |
All-cause mortality within 30 days for Medtronic Dissection Trial subjects with the complicating factor of rupture was 0.0% (0 out of 10 subjects) as reported in Table 27 and all-cause mortality within 30 days for subjects with the complicating factor of ischemia was 10% (4 out of 40 subjects) as reported in Table 28.
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Table 27. All-Cause Mortality within 30 Days for Medtronic Dissection Trial Subjects with the Complicating Factor of Rupture
| | % (m/n) [95% UCL]^{1, 2, 3} |
| --- | --- |
| 30-day All-Cause Mortality | 0.0% (0/10) [25.9%] |
| ^{1}95% Upper Confidence Limit (UCL) was calculated using an exact method based on the binomial distribution. ^{2}Based on the number of evaluable subjects. Subjects will be considered unevaluable if they are withdrawn before the lower limit of the 30-day follow-up window (16 days) or they are lost to follow-up before the lower limit of the 30-day follow-up window (16 days) and had no contact thereafter. ^{3}Based on CEC adjudicated data | |
Table 28. All-Cause Mortality within 30 Days for Medtronic Dissection Trial Subjects with the Complicating Factor of Ischemia Only
| | % (m/n) [95% UCL]^{1, 2, 3} |
| --- | --- |
| 30-day All-Cause Mortality | 10.0% (4/40) [21.4%] |
| ^{1}95% Upper Confidence Limit (UCL) was calculated using an exact method based on the binomial distribution. ^{2}Based on the number of evaluable subjects. Subjects will be considered unevaluable if they are withdrawn before the lower limit of the 30-day follow-up window (16 days) or they are lost to follow-up before the lower limit of the 30-day follow-up window (16 days) and had no contact thereafter. ^{3}Based on CEC adjudicated data | |
### Secondary Observations
The device was delivered and deployed successfully in all 50 subjects (100.0%) enrolled in the Medtronic Dissection Trial. The proximal entry tear was successfully covered in all subjects. There were no incidents of post-operative rupture. The all-cause mortality was 14.6% at 12 months. Four (4) subjects underwent secondary endovascular procedures within 12 months. Twenty three (23) subjects (23/49, 46.9%) had a serious adverse event reported within 12 months.
The trial data demonstrated favorable remodeling of the stented segment of the aorta after TEVAR. Beyond the stented segment, a trend towards positive remodeling was seen.
Of the nine (9) subjects who had perfusion of the false lumen at the 12-month visit, seven (7) were cases of continuing perfusion and one (1) was a case of new false lumen perfusion. The type of perfusion could not be ascertained in one (1) subject.
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**Table 29. Secondary Observations**
| | % (m/n) |
| --- | --- |
| Successful Delivery and Deployment of the Stent Graft^{1} | 100.0% (50/50) |
| Coverage of Proximal Entry Tear at Implant^{1} | 100.0% (50/50) |
| Adverse Events within 30 Days^{1} | 52.0% (26/50) |
| Non-serious Adverse Events | 16.0% (8/50) |
| Device related | -- |
| Procedure related | 16.0% (8/50) |
| Dissection related | 4.0% (2/50) |
| Serious Adverse Events | 38.0% (19/50) |
| Device related | 4.0% (2/50) |
| Procedure related | 20.0% (10/50) |
| Dissection related | 28.0% (14/50) |
| Rupture within 30 Days^{1} | -- |
| Secondary Procedures within 12 Months^{2} | |
| Secondary Endovascular Procedures related to the Dissection^{3} | 6.3% (3/48) |
| Secondary Endovascular Procedures not related to the Dissection^{4} | 2.1% (1/48) |
| Open Repair of Retrograde Type A Dissection | 4.2% (2/48) |
| Conversion to Open Repair for Descending Dissection | -- |
| LSA Bypass | 4.2% (2/48) |
| Adverse Events within 12 Months^{2} | 59.2% (29/49) |
| Non-serious Adverse Events | 16.7% (8/48) |
| Device related | -- |
| Procedure related | 16.7% (8/48) |
| Dissection related | 4.2% (2/48) |
| Serious Adverse Events | 46.9% (23/49) |
| Device related | 6.3% (3/48) |
| Procedure related | 20.8% (10/48) |
| Dissection related | 34.7% (17/49) |
| Rupture within 12 Months^{2} | -- |
| All-Cause Mortality within 12 Months^{2,5} | 14.6% (7/48) |
| Continuing or New False Lumen (FL) Perfusion at 6 Month Visit^{6} | |
| Core Lab Reported | 39.4% (13/33) |
| Continuing or New False Lumen (FL) Perfusion at 12 Month Visit^{6} | |
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Table 29. Secondary Observations
| | % (m/n) |
| --- | --- |
| Core Lab Reported | 27.3% (9/33) |
| ¹Based on number of ITT subjects with available data ²Based on the number of evaluable subjects. Subjects will be considered unevaluable if they are withdrawn before the lower limit of the 12 months follow-up window (275 days) or they are lost to follow-up before the lower limit of the 12 months follow-up window (275 days) and had no contact thereafter. ³Additional endovascular device placed ⁴LSA plug ⁵Based on CEC adjudicated data ⁶Based on the number of subjects with evaluable imaging at follow-up visit ⁷Site Reported and Core Lab Reported Table | |
### Summary of Deaths
Table 30 below summarizes the eight (8) deaths that have occurred to date in this subject population. Four (4) of the deaths occurred within 30 days of the procedure. Seven (7) occurred in the first 12 months and a single death has occurred post 365 days.
Table 30. Listing of Deaths
| Implant to Death (days) | Cause of Death Site Reported | Death Relatedness¹ Site Reported | Death Relatedness¹ CEC Adjudicated |
| --- | --- | --- | --- |
| 0 | Cardiac Tamponade² | Procedure Related | Device Related, Procedure Related, Dissection Related |
| 1 | Mesenteric Ischemia In Totalis³ | Dissection Related | Dissection Related |
| 9 | Sepsis⁴ | Not Related | Procedure Related, Dissection Related |
| 26 | Pulmonary Embolism⁵ | Not Related | Procedure Related, Dissection Related |
| 71 | Cardiac Arrest⁶ | Not Related | Not Related |
| 87 | Pneumonia⁷ | Not Related | Dissection Related |
| 124 | Cardiac Arrest⁸ | Not Related | Procedure Related |
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Table 30. Listing of Deaths
| Implant to Death (days) | Cause of Death Site Reported | Death Relatedness^{1} Site Reported | Death Relatedness^{1} CEC Adjudicated |
| --- | --- | --- | --- |
| 432 | Natural Causes^{9} | Not Related | Not Related |
$^{1}$Relationship to Device/Procedure/Dissection
Site and CEC Adjudicated Reported Table
$^{2}$The subject had a large pericardial effusion with acute cardiac tamponade most likely due to injury by a guidewire or catheter. Underlying causes/conditions were listed as cardiac arrest, ascending aortic dissection and ascending aortic aneurysm.
$^{3}$The subject was diagnosed with mesenteric ischemia in totalis. Immediate cause of death was identified as multi-system organ failure due to or as a consequence of an acute complicated Type B dissection.
$^{4}$The subject's immediate cause of death was sepsis, with contributing causes listed as pneumonia, respiratory failure and descending aortic aneurysm. In addition, CT data was suggestive of a stroke. See Table 37 for additional information.
$^{5}$The subject had pulmonary embolism due to or as a consequence of a DVT and AAA repaired with stents.
$^{6}$The subject had a sudden cardiac arrest in spite of gradual improvement following treatment.
$^{7}$The subject experienced fever, abdominal pain and abnormal LFTs prior to death whose cause was reported to be pneumonia.
$^{8}$The subject's immediate cause of death was identified as cardiac arrest due to or as a consequence of abdominal sepsis with a contributing cause of sacral decubitus ulcer.
$^{9}$In addition to aortic dissection, the subject experienced CHF, COPD, DVT and RA.
### Adverse events that occurred in the PMA clinical study
Only those adverse events and serious adverse events that were related to the device, to the implant procedure and/or to the aortic disease and serious adverse events that lead to death, regardless if they are related to the device, procedure or the aortic disease, were reported by the sites. Thirty eight percent of eligible subjects experienced an SAE within 30 days and 19.6% experienced an SAE between 31 and 365 days. Error! Reference source not found. lists the number of subjects who experienced one or more SAEs. In addition to the SAEs reported by the sites, those adverse events that did not meet the criteria of an SAE were reported as AEs. Sixteen percent of eligible subjects experienced an AE (excluding SAEs) within 30 days where as 2.2% experienced an AE between 31 and 365 days. These events are listed in Table 31. A subject may have experienced multiple adverse events, and in different subcategories; therefore, the number of subjects in each category may not be the sum of those in each subcategory. Each subject was only counted once in each subcategory. An adverse event may have been reported as related to one or more of the following: device, dissection or procedure. In cases where the AE was reported to be related to more than one category, it was included in all applicable AE tables. Therefore, the same event may appear in the device-related, procedure-related or dissection-related SAE tables.
All AEs and SAEs are further categorized based on the relatedness to the device, procedure or dissection in the following section.
Table 31. Subjects with Serious Adverse Events by Date of Onset
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| Category | 0 to 30 Days % (m/n)^{1} | 31 to 365 Days % (m/n)^{1} |
| --- | --- | --- |
| Subjects experiencing one or more SAE^{2} | 38.0% (19/50) | 19.6% (9/46) |
| Cardiac Disorders | 2.0% (1/50) | 4.3% (2/46) |
| Cardiac Arrest | -- | 4.3% (2/46) |
| Cardiac Tamponade | 2.0% (1/50) | -- |
| Gastrointestinal Disorders | 4.0% (2/50) | -- |
| Ileus | 2.0% (1/50) | -- |
| Intestinal Ischaemia | 2.0% (1/50) | -- |
| General Disorders And Administration Site Conditions | -- | 2.2% (1/46) |
| Death | -- | -- |
| Continued Perfusion from a Branch Vessel requiring Treatm…
