RelayPro Thoracic Stent-Graft System

P200045S002 · Bolton Medical, Inc. · MIH · Mar 7, 2023 · Cardiovascular

Device Facts

• Record ID: P200045S002
• Device Name: RelayPro Thoracic Stent-Graft System
• Applicant: Bolton Medical, Inc.
• Product Code: MIH · Cardiovascular
• Decision Date: Mar 7, 2023
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Indications for Use

The Relay®Pro Thoracic Stent-Graft System is indicated for the endovascular repair of all lesions of the descending thoracic aorta in patients having appropriate anatomy, including: Iliac or femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories; Non-aneurysmal aortic neck diameter in the range of: 20 – 42 mm for fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers and dissections 19 – 42 mm for traumatic aortic injuries; Proximal landing zone (non-aneurysmal proximal aortic neck lengths for fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers or non-dissected length of aorta proximal to the primary entry tear for dissections and length of aorta proximal to the tear for traumatic aortic injuries) of: 15 mm for the 22 – 28 mm device diameters (Bare Stent Configuration) 20 mm for the 30 – 38 mm device diameters (Bare Stent Configuration) 25 mm for the 40 – 46 mm device diameters (Bare Stent Configuration) 25 mm for the 22 – 38 mm device diameters (Non-Bare Stent Configuration) 30 mm for the 40 – 46 mm device diameters (Non-Bare Stent Configuration) Non-aneurysmal distal aortic neck lengths for fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers of: 25 mm for the 24 – 38 mm device diameters 30 mm for the 40 – 46 mm device diameters Non-aneurysmal distal landing zone of 20 mm for traumatic aortic injuries (22 mm – 46 mm device diameters) and dissections (24 mm – 46 mm device diameters) The Relay®Pro Thoracic Stent-Graft System (NBS configuration) is indicated for the endovascular distal extension of the Thoraflex Hybrid device.

Device Story

RelayPro Thoracic Stent-Graft System treats descending thoracic aorta (DTA) lesions (aneurysms, PAUs, Type B dissections, traumatic injuries). System comprises self-expanding Nitinol stents sutured to woven polyester fabric; available in proximal bare stent or non-bare stent (NBS) configurations. Implants preloaded into delivery system; advanced under fluoroscopy via femoral/iliac access. Deployment creates blood flow channel, excluding lesion. NBS configuration includes support wires (32-46mm diameters) to control expansion and ensure wall apposition. Used in hospital settings by vascular surgeons/interventionalists. Output is physical exclusion of aortic lesion; clinical benefit is minimally invasive repair of life-threatening aortic pathology, reducing need for open surgery.

Clinical Evidence

Clinical evidence from two prospective, multicenter, single-arm studies: Pro-D (N=56, Type B dissection) and Pro-T (N=50, traumatic injury). Pro-D primary endpoint (30-day all-cause mortality) was 1.8% (95% CI: 8.2%), meeting 25% performance goal. Pro-T primary endpoint (30-day all-cause mortality) was 2.0% (95% CI: 0.1-10.6%), below 8% expected rate. Secondary endpoints included technical success, MAEs (stroke, renal failure, paraplegia/paresis), endoleaks, and secondary interventions.

Technological Characteristics

Materials: Nitinol stents, woven polyester fabric, platinum-iridium radiopaque markers. Sensing/Actuation: Self-expanding stent-graft. Energy: None (mechanical deployment). Connectivity: None. Sterilization: Not specified. Software: None. Form factor: 22-46mm diameters, straight/tapered/reverse-tapered configurations. Delivery system: Coaxial sheaths/catheters, 90cm working length, 19-23 French OD.

Indications for Use

Indicated for endovascular repair of all descending thoracic aorta lesions in patients with appropriate anatomy, including fusiform/saccular aneurysms, penetrating atherosclerotic ulcers, Type B dissections, and traumatic aortic injuries. Contraindicated in patients with known allergy to Nitinol, polyester, or platinum-iridium, or conditions threatening graft infection.

Reference Devices

• Thoraflex™ Hybrid (P210006)
• Relay®Pro Thoracic Stent-Graft System (P200045)

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: Relay®Pro Thoracic Stent-Graft System

Device Procode: MIH

Applicant's Name and Address: Bolton Medical, Inc.
799 International Parkway
Sunrise, FL 33325 USA

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P200045/S002

Date of FDA Notice of Approval: March 7, 2023

The original PMA (P200045) was approved on August 5, 2021 and is intended for endovascular repair of fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers in the descending thoracic aorta (DTA) in patients having appropriate anatomy. The Summary of Safety and Effectiveness Data (SSED) to support the original approval is available on the CDRH website and are incorporated by reference here. Please see the approval order on the CDRH website for the original Indications for Use.

The current supplement was submitted to expand the indication for the Relay®Pro Thoracic Stent-Graft System for the endovascular repair of isolated lesions of the descending thoracic aorta (DTA) to include the treatment of all lesions of the DTA, including Type B dissections and traumatic injuries. The study design and approach is consistent with other endovascular grafts that are currently marketed with these indications.

The current supplement was also submitted to expand the indications for the Relay®Pro Thoracic Stent-Graft System for the distal extension of the Thoraflex™ Hybrid device. The original PMA (P210006) for Thoraflex™ Hybrid was approved on April 19, 2022 and is intended for the open surgical repair or replacement of damaged or diseased vessels of the aortic arch and descending aorta, with or without involvement of the ascending aorta, in cases of aneurysm and/or dissection.. The Summary of Safety and Effectiveness Data (SSED) to support the use of the Relay®Pro Thoracic Stent-Graft System with the Thoraflex™ Hybrid is available on the CDRH website and are incorporated by reference here.

The RelayPro device presented in this PMA supplement is the same design as that approved in the original PMA with the addition of the 22mm device configuration.

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## **II. INDICATIONS FOR USE**

The Relay®Pro Thoracic Stent-Graft System is indicated for the endovascular repair of all lesions of the descending thoracic aorta in patients having appropriate anatomy, including:

- Iliac or femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories;
- Non-aneurysmal aortic neck diameter in the range of:

- 20 – 42 mm for fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers and dissections
- 19 – 42 mm for traumatic aortic injuries;

- Proximal landing zone (non-aneurysmal proximal aortic neck lengths for fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers or non-dissected length of aorta proximal to the primary entry tear for dissections and length of aorta proximal to the tear for traumatic aortic injuries) of:

- 15 mm for the 22 – 28 mm device diameters (*Bare Stent Configuration*)
- 20 mm for the 30 – 38 mm device diameters (*Bare Stent Configuration*)
- 25 mm for the 40 – 46 mm device diameters (*Bare Stent Configuration*)

- 25 mm for the 22 – 38 mm device diameters (*Non-Bare Stent Configuration*)
- 30 mm for the 40 – 46 mm device diameters (*Non-Bare Stent Configuration*)

- Non-aneurysmal distal aortic neck lengths for fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers of:

- 25 mm for the 24 – 38 mm device diameters
- 30 mm for the 40 – 46 mm device diameters

- Non-aneurysmal distal landing zone of 20 mm for traumatic aortic injuries (22 mm – 46 mm device diameters) and dissections (24 mm – 46 mm device diameters)

The Relay®Pro Thoracic Stent-Graft System (NBS configuration) is indicated for the endovascular distal extension of the Thoraflex Hybrid device.

## **III. CONTRAINDICATIONS**

The Relay®Pro Thoracic Stent-Graft System is contraindicated in the following:

- Patients with a known allergy or intolerance to device materials (Nitinol, polyester, platinum-iridium).
- Patients with a condition that threatens to infect the graft

## **IV. WARNINGS AND PRECAUTIONS**

The warnings and precautions can be found in the Relay®Pro Thoracic Stent-Graft System labeling.

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V.

# DEVICE DESCRIPTION

The Relay®Pro Thoracic Stent-Graft System (referred to as RelayPro hereafter) is designed to treat fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers, Type B dissections and traumatic injuries in the descending thoracic aorta. The RelayPro Stent-Graft System consists of two types of implants, namely the proximal bare stent configuration and the non-bare stent (NBS) configuration.

Each patient receives at least one RelayPro Stent-Graft (Figure 1). Each implant configuration is preloaded into its own RelayPro delivery system that is advanced under fluoroscopy to the location of the lesion. Upon deployment the stent-graft creates a blood flow channel, excluding the lesion from blood pressure and flow.

# RelayPro Stent-Grafts

All stent-grafts are comprised of self-expanding Nitinol stents sutured to a woven polyester fabric. The stent scaffold is a series of sinusoidal springs stacked in a tubular configuration. These stents are spaced along the length of the graft fabric to provide radial support and allow for the self-expansion of the stent-grafts. A spiraled (“S” shaped) Nitinol strut is sewn to the proximal section of the fabric to provide longitudinal support. The stents and the curved wire are sewn to the graft fabric with polyester surgical grade suture. Radiopaque markers are placed on the stent-graft to aid in visualization and accurate placement.

The RelayPro Stent-Graft is available in two proximal configurations: the proximal bare stent and non-bare stent (NBS). Other than the proximal configuration, the two implants are identical in design as described above.

The proximal bare stent configuration incorporates a bare stent that is mostly uncovered and is made of a slightly larger Nitinol wire than the other stents in the implant. The proximal apexes are designed with larger radii of curvature as compared to all other apexes on all other stents. Additionally, the bare stent has the lowest radial load of all stents on the RelayPro stent-graft. The combination of the large apexes and low radial force of the bare stent is intended to minimize the stress on the aortic wall. There is one bare stent per implant. The proximal stent (just distal to the bare stent) has the highest radial load and is designed to seal with the aortic wall. There are two proximal stents per implant.

The NBS configuration incorporates a crown stent that consists of a series of apices that are connected by flat sections. The crown stent is designed to support the edge of the graft to appose the vessel wall and to minimize graft infolding. There is one crown stent per implant. The NBS proximal stent (just distal to the crown stent) has the same design intent as proximal stent in the proximal bare stent configuration and has a slightly modified design. There are two NBS proximal stents per implant.

The RelayPro Stent-Graft is available in the following configurations and sizes maximizing device selections available to the physician:

- Two proximal configurations: Proximal Bare Stent & Non-Bare Stent (NBS)

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- Covered Lengths (Bare Stent): 100mm (± 10mm depending on graft diameter) to 250 mm
- Covered Lengths (Non-Bare Stent): 109mm (± 10mm depending on graft diameter) to 259mm
- Diameters: 22mm – 46mm in 2 mm increments
- Straight and Tapered Configurations

○ Straight: Consistent diameter through the implant length

○ Standard Taper: Diameter of device decreases proximal to distal (typical 4mm transition; availability from 2mm and up to 18mm transition)

○ Reverse Taper: Diameter of device increases proximal to distal (availability from 2mm and up to 18mm transition)

Figure 1. RelayPro Thoracic Stent-Graft, with bare stent and non-bare stent, illustrating stents and spiral support strut


### Delivery System Description

The RelayPro Delivery System consists of a series of coaxially-arranged sheaths and catheters (outer introduction sheath, inner delivery sheath, through lumen), handle and apex release mechanism. The stent-graft is constrained within the inner sheath, which is further constrained within the outer sheath. The tapered tip and introducer sheath have a lubricious hydrophilic coating. The radiopaque, polymeric outer sheath is tracked over a guidewire to facilitate introduction of the device through the femoral and iliac arteries. Once the outer sheath reaches the distal end of the treatment site, the deployment grip of the delivery system is advanced to exit the inner sheath from the outer sheath. The inner sheath is advanced to the proximal landing zone in preparation for deployment. The inner sheath, which is connected to the delivery catheter and the delivery handle, can be retracted to deploy the constrained stent-graft

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in a controlled fashion. The apex release mechanism constrains the most proximal stent of the stent-graft. Sliding the outer control tube over the guidewire lumen after the deployment from the inner sheath controls this mechanism. This provides a controlled apposition of the stent to the vessel wall.

The delivery systems used for the RelayPro NBS and Bare Stent configurations are functionally and operationally equivalent. There are minor differences to accommodate the NBS configuration which do not change the mode of operation. **Figure 2** illustrates the delivery system for the Bare Stent and NBS configuration. Item 16 in **Figure 2** (support wires) are not present in the Bare Stent configuration delivery system. The two Nitinol wires, called support wires, control the expansion of the inferior portion of the stent-graft, which helps avoid asymmetrical deployment of the NBS configuration. The support wires are attached to the delivery system catheter at one end. The other end of the support wires are atraumatic teardrop-shaped and are tethered to the inferior portion of the graft with loops of suture. The support wires control the expansion of the proximal end of the stent-graft to ensure proper apposition against the anatomical inner curvature and are for NBS graft diameters 32mm to 46mm only. In addition, the design of Item 2 in the figure (apex holder) differs slightly between the configurations. The delivery system is provided in outer diameters ranging from 19 up to 22 French for the Bare Stent Configuration and 23 French for the NBS Configuration, depending on the corresponding stent-graft diameter, with a working length of 90 cm.


**Figure 2. RelayPro Bare and Non-Bare Stent Configuration Delivery System**

| 1. Delivery System Tip | 9. Flush Port |
| --- | --- |
| 2. Apex Holder | 10. Deployment Grip |
| 3. Inner Sheath | 11. Controller |
| 4. Outer Sheath | 12. Stainless Steel Rod |
| 5. Radiopaque Marker | 13. Apex Holder Knob |

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6. Front Nose Cap
7. Gray Grip
8. Handle Body
14. Guidewire Luer
15. Arrow Marker
16. Support Wire (Non-Bare Stent only)

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several alternatives for the treatment of lesions in the descending thoracic aorta including medical management, open surgical repair, and endovascular repair using other endovascular grafts. 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. For traumatic injuries, surgical or endovascular intervention is required to prevent death.

# VII. MARKETING HISTORY

The RelayPro Thoracic Stent-Graft for the treatment of aneurysms and penetrating atherosclerotic ulcers (PAU) was approved August 5, 2021 (P200045). The device is commercially available in countries such as the European Union, Chile, Colombia, Hong Kong, India, Japan, Lebanon, Singapore, South Africa, Thailand, UK and Vietnam since 2018.

The RelayPro Thoracic Stent-Graft has not been withdrawn from the market for any reason related to its safety or effectiveness.

# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device:

| Table 1. Potential Adverse Events | |
| --- | --- |
| Access Failure | Infection / Sepsis |
| Allergic Reaction (to contrast, antiplatelet therapy, stent-graft materials) | Intercostal pain |
| Amputation | Intramural Hematoma |
| Anesthetic reactions/complications (e.g., aspiration) | Ischemia (spinal cord, perfusion pathways) |
| Aneurysm Sac Enlargement | Limb ischemia |
| Aneurysm / Lesion Rupture | Lymphocele |
| Angina | Neuropathy |
| Aortic vessel damage (perforation, dissection, bleeding, rupture) | Pain |

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| Table 1. Potential Adverse Events | |
| --- | --- |
| Arteriovenous fistula / aorto-esophageal fistula | Paralysis/Paresthesia/Paraparesis/Paraplegia/Spinal Cord Shock |
| Blindness | Perforation |
| Blood Loss | Peripheral Nerve injury |
| Bowel complications (e.g., adynamic ileus, transient ischemia, infarction, obstruction, necrosis) | Persistent false lumen flow |
| Cardiac events (e.g., arrhythmia, tachyarrhythmia, cardiac tamponade, congestive heart failure, myocardial infarction, hypotension, hypertension, tachycardia, bradycardia) | Post Implantation Syndrome |
| Catheter Breakage | Post-procedural bleeding |
| Cerebral vascular accident (stroke) | Pseudoaneurysm |
| Change in mental status | Pulmonary complications |
| Claudication (e.g., buttock, lower limb) | Pulmonary embolism |
| Coagulopathy | Radiation overexposure or reaction |
| Compartment Syndrome | Reaction to anesthesia |
| Contrast toxicity / anaphylaxis | Reaction/pain at catheter insertion site |
| Conversion to Open Repair | Renal failure or Complications |
| Death | Reoperation |
| Delivery system failure | Seizure |
| Deployment failure (partial or inaccurate deployment) | Seroma |
| Device Dehiscence | Shock |
| Device Insertion or Removal Difficulty | Stenosis of native vessel |
| Dissection extension | Stent fracture / break |
| Dysphagia | Stent-Graft failure (e.g., improper component placement, poor conformability of the graft to the vessel wall, graft material wear or tear, suture break, dilation, erosion, graft twisting or kinking, stent-graft thrombosis / occlusion, puncture, perigraft flow) |
| Edema | Stent-Graft Infection |
| Embolism (micro and macro) with transient or permanent ischemia or infarction | Stent-Graft Migration |
| Endoleak | Tissue Necrosis |
| Fever and localized inflammation | Transient Ischemic Attack |
| Fistulas | Unintentional Dissection Septum Rupture |
| Gastrointestinal complications | Vascular Spasm |

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| **Table 1. Potential Adverse Events** | |
| --- | --- |
| Genitourinary complications (e.g., ischemia, erosion, femoral-femoral artery thrombosis, fistula, incontinence, hematuria, infection) | Vascular Trauma (perforation / dissection) |
| Hematoma (surgical) | Vessel Damage |
| Hemorrhage | Vessel Dissection |
| Hepatic failure | Vessel Occlusion/Thrombosis |
| Impotence | Wound complications (dehiscence, infection, hematoma, seroma, cellulitis) |
| Incision site complications | |

For the specific adverse events that occurred in the clinical study, please see **Sections D 1.2 and H 1.2 Secondary Safety Endpoints** below.

## **IX. SUMMARY OF NONCLINICAL STUDIES**

Nonclinical studies were completed to evaluate the RelayPro device, including non-clinical bench testing, biocompatibility, sterilization, packaging, shelf-life (2 years), and animal studies. The SSED containing the Nonclinical studies to support the aneurysm indication (P200045) for the RelayPro device is available on the CDRH website.

Bolton Medical is seeking approval of an expanded indication using the same commercially approved RelayPro Thoracic Stent Graft System. No changes have been made to the product design or specifications, other than the addition of the 22mm configuration. Most pre-clinical studies previously provided in P200045 and P210006 are applicable and were adequate to support the indication expansion (e.g., testing included the full device size matrix; the 22mm configuration has the same migration resistance and radial force acceptance criteria as the 24-28mm device configurations). In addition, new studies were conducted for the following to support the expanded indications:

- Fatigue and Durability – Computational Analyses

### **A. Laboratory Studies**

To support the expanded indications, RelayPro underwent testing for design verification and validation, including long-term durability. Testing was performed in accordance with ISO 25539-1: 2017, “*Cardiovascular implants – Endovascular devices – Part 1: Endovascular prostheses*” and ISO 25539-1: 2003/A1, “*Cardiovascular implants – Endovascular devices – Part 1: Endovascular prostheses, Amendment 1: Test Methods.*” For evaluation of the RelayPro, a subset of device components and sizes were used for each test or alternatively, the worst-case configuration /size was selected. A four-corners approach was utilized for sample selection. This sample selection represented the full size range available for RelayPro. A summary of the new studies is provided in **Table 2**.

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**Table 2. Non-Clinical Testing: Implant**

| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Fatigue and Durability – Computational Analyses | Finite element analysis (FEA) was used to compute the maximum strains in all of the RelayPro design’s sizes when subjected to catheter loading and maximum alternating strains in an *in-vivo* pulsatile loading environment. | Characterization study. The worst-case component size was identified and used to select the worst-case prosthesis oversizing for *in-vitro* fatigue testing. Worst-case identification also considered differences in vascular compliance between transection and dissection populations. Devices were evaluated in single and overlapped configurations. | Pass |
| Fatigue and durability – *In-vitro* testing | Pulsatile Fatigue Testing^{1}: To evaluate the long-term durability of the stent-graft design following 10 years simulated testing under clinically relevant loading conditions. | The samples must not exhibit physical damage that would represent a failure of their safety or function due to: 1. Component deformation, separation or fractures leading to ineffective proximal or distal seals, migration or severed pieces into the bloodstream 2. Fabric holes larger than 0.5 mm^{2} 3. Modular disjunctions 4. Compromised luminal integrity due to twisting or component collapse All anomalies must be studied on a case-by-case basis. Anomalies due to test artifacts will not be representative of failure in safety or function of the design. | Pass |
| | Dynamic Bending Testing^{2}: To evaluate the long-term durability of the stent-graft design following 10 years simulated testing under clinically relevant loading conditions. | | Pass |

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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | | Devices were evaluated in single and overlapped configurations. | |

$^{1}$ Pulsatile Fatigue Testing used to support aneurysm, dissection, and transection indications.

$^{2}$ Dynamic Bending Testing used to support aneurysm and dissection indications; data collected for aneurysm indication was leveraged to support transection indication.

## X. SUMMARY OF PRIMARY CLINICAL STUDIES

The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of endovascular repair of fusiform aneurysms and saccular aneurysms/penetrating atherosclerotic ulcers in the descending thoracic aorta with the RelayPro Thoracic Stent-Graft System in the US and Japan (**P200045**) [shall be referred to as Pro-A]; data from the Pro-A clinical study were the basis for the PMA approval decision. A second primary study was conducted to support the expanded indication to include treatment of blunt traumatic aortic injury (shall be referred to as Pro-T). A third primary study was conducted to support the expanded indication to include treatment of all lesions of the descending thoracic aorta (DTA), including Type B aortic dissections (shall be referred to as Pro-D). A summary of the clinical studies is presented below.

**Table 3: Summary of RelayPro Primary Clinical Studies**

| Pivotal Study | Study Design | Objective | Number of Sites with Enrollment | Number of Subjects |
| --- | --- | --- | --- | --- |
| Pro-A: Aneurysm/PAU | Prospective, multi-center, non-blinded, non-randomized, single-arm multinational (US, Japan) | To evaluate the safety and effectiveness of the RelayPro Thoracic Stent-Grafts in subjects with aneurysms and PAUs within the descending thoracic aorta. | 36 | 110 |
| Pro-T: Blunt Thoracic Aortic Injury (BTAI) | Prospective, non-blinded, non-randomized, single-arm, US multicenter | To evaluate safety and effectiveness of the RelayPro Thoracic Stent-Graft for the treatment of traumatic injury of the descending thoracic aorta. | 16 | 50 |
| Pro-D: Acute, Complicated Type B Dissection | Prospective, non-blinded, non-randomized, single-arm, US multicenter | To evaluate safety and effectiveness of the RelayPro Thoracic Stent-Graft for the treatment of acute, complicated Type B aortic dissections. | 22 | 56 |

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## **A. Study Design – Pro-D**

Patients were treated between September 7, 2017 and September 3, 2021. The database for this panel track supplement reflected data collected through June 3, 2022 and included 56 US patients. There were 22 US investigational sites.

The RelayPro-Dissection (Pro-D) clinical study is a prospective, multicenter, single-arm, non-blinded, non-randomized study of the treatment of patients with acute, complicated Type B aortic dissections with the RelayPro Thoracic Stent-Graft System.

The primary endpoint is the rate of all-cause mortality at 30-days post procedure. The results were tested against a performance goal of 25%, consistent with the performance goal of other endovascular graft pivotal studies for acute, complicated Type B dissections. The hypothesis tested for the primary endpoint was:

Null hypothesis ($H_0$): $p \geq 0.25$

Alternative Hypothesis ($H_A$): $p < 0.25$

Interim analyses were planned to be completed when 50, 65, and 80 subjects reached 30 days of post-procedure follow-up. With respect to stopping for success according to the interim analysis plan, a p-value of 0.01317 or less would be required to cross the boundary based on data from the first 50 subjects.

External evaluation groups were used during the course of the Pivotal Study, which are described below:

- *Independent Imaging Core Laboratory:* The Core Laboratory assessed follow-up imaging endpoints, including endoleak, migration, aneurysm sac size increase, patency, stenosis, and stent fracture.
- *Clinical Events Committee and Data Safety Monitoring Board:* An independent Clinical Events Committee (CEC) and a separate, independent Data Safety Monitoring Board (DSMB) were responsible for assuring the study was conducted ethically, and that the health and welfare of each study patient was protected. The CEC adjudicated events, as specified in the CEC Charter, as identified by the Medical Monitor from regular review of all reported adverse events and classified them as related or not related to the device or the procedure. The DSMB met separately to review the safety data in aggregate and assess the overall safety of the study. The DSMB also assessed whether the continuation of enrollment was appropriate, and if not, whether protocol modifications were necessary or whether the study should be halted.

### **1. Clinical Inclusion and Exclusion Criteria**

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

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- Age ≥18 years.
- Have an acute (symptom onset to diagnosis within 2 weeks), complicated Type B aortic dissection (entire dissection is distal to the left subclavian artery), including those with multiple entry tears, with clinical or imaging evidence of at least one of the following:
o Malperfusion of the viscera, kidneys, spinal cord, or lower extremities;
o Aortic rupture.
- Proximal and distal landing zones with diameter between 19 mm and 42 mm.
- Patient's anatomy must meet all of the following anatomical criteria:
o Proximal landing zone distal to the left common carotid and a distal attachment zone proximal to the origin of the celiac artery.
▪ Dissection is permitted in the distal attachment zone but is not permitted in the proximal attachment zone.
o The length of the proximal landing zone depends on the intended stent-graft diameter, and landing zone should be:
▪ 15 mm for 22 – 28 mm RelayPro grafts with bare stent (20 mm for RelayPro grafts with non-bare stent).
▪ 20 mm for 30 – 46 mm RelayPro grafts with bare stent (25 mm for RelayPro grafts with non-bare stent).
▪ Proximal to non-dissected segment (healthy zone)
o The distal attachment zone should be 20 mm for all RelayPro grafts.
o Coverage of the left subclavian artery (LSA) is permitted with mandatory revascularization if patent left internal mammary artery (LIMA) bypass or left upper extremity (LUE) arteriovenous graft or anomalous vertebral artery off the aorta. Revascularization must be performed prior to device placement, and may occur during implant procedure, provided it is before coverage of the LSA by the endograft.
- Proximal landing zone containing a straight segment (non-tapered, non-reverse-tapered, defined by <10% diameter change) with lengths equal to or greater than the required attachment length for the intended device.
- Vascular dimensions (e.g., aortic diameters, length from left subclavian to celiac artery) must be in the range that can be treated with the RelayPro Thoracic Stent-Grafts (able to deliver device to the location of treatment as described in the IFU).
- Adequate iliac or femoral artery access for introduction of the RelayPro Delivery System. Alternative methods to gain proper access may be utilized (e.g., iliac conduit).
- Patient willing to comply with the follow-up evaluation schedule.
- Patient (or Legally Authorized Representative, LAR) agrees to sign an Informed Consent Form prior to treatment.

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

- • Diagnosis of traumatic injury or transection of the descending thoracic aorta.
- • Significant stenosis, calcification, thrombus, or tortuosity of intended fixation sites that would compromise fixation or seal of the device.
- • Planned coverage of left carotid or celiac arteries; or anatomic variants that may compromise circulation to the carotid, vertebral, or innominate arteries after device placement, and are not amenable to subclavian revascularization.
- • Prior endovascular or surgical repair in the descending thoracic aorta. The device may not be placed within any prior endovascular or surgical graft.
- • Concomitant aneurysm/disease of the ascending aorta, aortic arch, or abdominal aorta, requiring repair. Dissection extension into the abdominal aorta is acceptable.
- • Prior abdominal aortic aneurysm repair (endovascular or surgical) that was performed less than 6 months prior to the planned stent implant procedure.
- • Major surgical or medical procedure within 30 days prior to the planned procedure or is scheduled for a major surgical or medical procedure within 30 days post implantation. This excludes any planned procedures for the prospective stent-graft placement.
- • Untreatable allergy or sensitivity to contrast media or device components, including metal stents.
- • Known or suspected connective tissue disorder.
- • Blood coagulation disorder or bleeding diathesis for which the treatment cannot be suspended for one week pre- and/or post-repair.
- • Coronary artery disease with unstable angina.
- • Severe congestive heart failure (New York Heart Association functional class IV).
- • Stroke and/or MI within 3 months of the planned treatment date.
- • Pulmonary disease requiring the routine (daily or nightly) need for oxygen therapy outside the hospital setting.
- • Acute renal failure (not associated with malperfusion due to aortic dissection) or chronic renal insufficiency, and not receiving dialysis.
- • Hemodynamically unstable.
- • Active systemic infection and/or mycotic aneurysm.
- • Bowel necrosis.
- • Morbid obesity or other condition that may compromise or prevent the necessary imaging requirements.
- • American Society of Anesthesiologists risk classification = V (Moribund patient not expected to live 24 hours with or without operation).
- • Less than two-year life expectancy.
- • Current or planned participation in an investigational drug or device study that has not completed primary endpoint evaluation.

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- Currently pregnant or planning to become pregnant during the course of the study.
- Medical, social, or psychological issues that Investigator believes may interfere with treatment or follow-up.

# 2. Follow-up Schedule

All patients were scheduled to return for follow-up examinations at 30 days (± 4 weeks), 6 months (± 8 weeks), 12 months (± 12 weeks) and annually (± 12 weeks) through 5 years postoperatively.

Table 4 summarizes the assessment requirements at each stage include preoperative, at treatment, at discharge and at each post-operative follow-up visit.

Additional assessments that were collected at each follow-up visit included:

- Device-related adverse events
- Aortic rupture
- Stent-graft migration, assessed by an Independent Core Laboratory
- Endoleak, assessed by an Independent Core Laboratory
- Aortic enlargement, assessed by an Independent Core Laboratory
- Stent-graft integrity, assessed by an Independent Core Laboratory
- Loss of stent-graft patency
- Conversion to open surgery
- Secondary interventions
- Aortic-related mortality

Table 4: Schedule of Assessments (Pro-D)

| | Screening | Treatment | Discharge | 1M ±4 weeks | 6M ±8 weeks | 12M ±12 weeks | 2, 3, 4, 5Y ±12 weeks |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Informed Consent | X | | | | | | |
| Medical History | X | | | | | | |
| Verify Inclusion/Exclusion Criteria | X | | | | | | |
| Physical Exam (including neurological assessment) | X | | | | | | |
| Pregnancy testing for female patients of childbearing potential | X | | | | | | |
| CT Scan with Contrast, or MRA | X | | | | | | |
| Angiogram | | X | | | | | |
| Clinical Utility Measures | | X | X | | | | |
| Examination of the incision site and assessment of healing | | | X | | | | |

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**Table 4: Schedule of Assessments (Pro-D)**

| | Screening | Treatment | Discharge | 1M ±4 weeks | 6M ±8 weeks | 12M ±12 weeks | 2, 3, 4, 5Y ±12 weeks |
| --- | --- | --- | --- | --- | --- | --- | --- |
| CT scan with/without contrast | | | | X* | X* | X* | X* |
| Chest X-Ray | | | | X | X | X | X |
| Adverse Event and device related events assessment | | X | X | X | X | X | X |

* MRI, combined with unenhanced CT, could be performed at follow-up visits for patients who could not receive contrast.

The key timepoints are shown below in the tables summarizing safety and effectiveness.

### 3. Clinical Endpoints

The primary endpoint is the rate of all-cause mortality at 30-days post procedure.

The primary endpoint was compared to a Performance Goal (PG) of 25%.

With regard to success/failure criteria, the Pro-D Study primary endpoint will be considered successful if the primary endpoint performance goal is met.

The following secondary analyses were completed using descriptive statistics:

*At the index procedure:*

- Technical Success defined as successful device delivery and deployment including withdrawal of the delivery system

*Through 1 month*

- Treatment success, defined as individual components and as a composite:
- Absence of major adverse events (MAEs), defined as:
- Stroke (disabling);
- Renal failure (excludes pre-existing);
- Paraplegia;
- Paraparesis;
- Absence of perfusion into the false lumen through the primary intimal tear;
- Absence of retrograde extension of the dissection;

*Through 1 month, 6 months, 12 months, and annually through 5 years;*

- Dissection treatment success, defined as individual endpoints and a composite:
- Absence of expansion (> 5mm) in the aorta that has an endograft, compared to the first post-procedural computed tomographic (CT) imaging study;

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○ Absence of aortic rupture;
○ Absence of dissection-related mortality;
○ Absence of MAEs including new ischemia due to branch vessel compromise;
○ Absence of false lumen perfusion separated by location:
▪ Proximal;
▪ Distal;
▪ Branch;
○ Absence of new aortobronchial/tracheal or aortoenteric fistula formation;
○ Absence of unintentional rupture of the dissection septum;
• Device imaging assessments, defined as:
○ Endoleaks;
○ Stent graft kinking or twisting;
○ Loss of stent-graft patency;
○ Misalignment;
○ Loss of integrity;
○ RelayPro stent fracture in the attachment zone;
○ Stent migration (> 10mm), compared to the first post-procedural CT;
• Incidence of open or endovascular dissection related secondary interventions to treat malperfusion, rupture, aneurysm formation, or aortic expansion

At 6 months, 12 months, and annually through 5 years, compared to the first post-procedural CT;

• Aortic expansion (> 5mm)
• Stent migration (> 10 mm)

### B. Accountability of PMA Cohort – Pro-D

At the time of database freeze, of the 56 patients enrolled in the Pro-D study, all 56 patients were implanted with the RelayPro Stent-Graft System and 56 were seen through discharge. Fifty-three (of 56) eligible patients (94.6%) had a 30-day visit with at least 85.7% of patients with adequate imaging to address endovascular graft parameters. Thirty-seven (of 51) patients had a 6-month visit with at least 58.8% with imaging adequate to address endovascular graft parameters. At the 12-month visit, 34 of 48 eligible patients had a visit performed with at least 62.5% with imaging adequate to address endovascular graft parameters. Additional visits and follow-up assessments have been obtained through 4-years and are provided in Table 5 below. Two patients are eligible for the 5-year visit; however, they have not yet returned for the visit.

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Table 5: Summary of Pro-D Compliance & Core Laboratory Imaging Follow-up

| Visit | Patient Follow-Up# | | | | Imaging | | Imaging Adequate † | | | | Events Within Window‡ | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Eligible for Visit | Visit Performed | No Visit* | Still in Window | CT Scan | X-Ray | Diameter | Endoleak | Migration | Fracture | Death | Lost to follow-up | Early Withdrawal | Not Yet Due | Patients with ≥1 Element |
| Index | 56 | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0 | 0 | 0 | 0 | 0 |
| 30D | 56 | 94.6% (53/56) | 5.4% (3/56) | 0 | 91.1% (51/56) | 87.5% (49/56) | 89.3% (50/56) | 85.7% (48/56) | 91.1% (51/56) | 92.9% (52/56)†† | 5 | 0 | 0 | 0 | 5 |
| 6M | 51 | 72.5% (37/51) | 27.5% (14/51) | 0 | 66.7% (34/51) | 62.7% (32/51) | 66.7% (34/51) | 58.8% (30/51) | 64.7% (33/51) | 66.7% (34/51) | 1 | 2 | 0 | 0 | 3 |
| 12M | 48 | 70.8% (34/48) | 29.2% (14/48) | 14.6% (7/48) | 66.7% (32/48) | 56.3% (27/48) | 66.7% (32/48) | 62.5% (30/48) | 64.6% (31/48) | 64.6% (31/48) | 1 | 1 | 0 | 10 | 12 |
| 2Y | 36 | 55.6% (20/36) | 44.4% (16/36) | 27.8% (10/36) | 52.8% (19/36) | 50.0% (18/36) | 52.8% (19/36) | 47.2% (17/36) | 50.0% (18/36) | 50.0% (18/36) | 2 | 2 | 0 | 12 | 18 |
| 3Y | 18 | 50.0% (9/18) | 50.0% (9/18) | 33.3% (6/18) | 38.9% (7/18) | 38.9% (7/18) | 38.9% (7/18) | 33.3% (6/18) | 38.9% (7/18) | 38.9% (7/18) | 0 | 0 | 0 | 10 | 10 |
| 4Y | 8 | 25.0% (2/8) | 75.0% (6/8) | 75.0% (6/8) | 25.0% (2/8) | 25.0% (2/8) | 25.0% (2/8) | 25.0% (2/8) | 25.0% (2/8) | 12.5% (1/8) | 0 | 0 | 0 | 6 | 6 |
| 5Y | 2 | 0 | 100.0% (2/2) | 100.0% (2/2) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |

NA – Not Applicable; LTFU, lost to follow-up;

The number of patients eligible for each visit are used for the denominator for the percentages of visits performed, imaging performed, as well as imaging adequate to assess the respective endovascular graft parameters.

# Site reported data. No Visit reflects patients who did not have a visit and/or imaging performed within the window. Still in Window reflects patients who have not yet reached the end of the analysis window and have not yet had a visit or imaging performed.

† Aortic Diameter and Migration assessments use 1 month as baseline. Eligible patients require valid value at 1 month and at the specified time point.

‡ These columns reflect patients who had visits within the specified window but were not eligible at the start of the next window due to death, loss to follow-up, conversion to open surgery, or early withdrawal. Please note that 2 patients had a conversion to open surgery and are counted in the Other column.

* One patient was indicated as having voluntarily withdrawn, but the date of withdrawal was not recorded. This patient was not counted as a withdrawal in this table as the patient has subsequently re-consented for participation.

†† There was one patient who had an x-ray but not a CT scan and three patients who had CTs but not an x-ray. Since fractures can be assessed from either imaging modality, the 51 CT scans plus the one x-ray without a CT scan gives a total of 52/56 patients with imaging adequate to assess fracture.

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### C. Study Population Demographics and Baseline Parameters

#### Demographics

The pivotal study population is 73.2% male (41/56), 53.6% black (30/56) and predominately younger; two thirds were under 65 with a mean age of 59.5±11.4 years.

**Table 6: Patient Demographics (Pro-D)**

| | Statistics | Pro-D Patients (N=56) |
| --- | --- | --- |
| **Sex** | | |
| Male | % (n/N) | 73.2% (41/56) |
| Female | % (n/N) | 26.8% (15/56) |
| **Age (years) at Treatment** | Mean ± SD (N) | 59.5 ±11.42 (56) |
| | Median (IQR) | 59.5 (51-68) |
| | Min - Max | 36 - 82 |
| **Age Group** | | |
| 18-64 years | % (n/N) | 66.1% (37/56) |
| 65-74 years | % (n/N) | 25.0% (14/56) |
| 75+ years | % (n/N) | 8.9% (5/56) |
| **Ethnic Group** | | |
| Not Hispanic/Latino | % (n/N) | 89.3% (50/56) |
| Hispanic/Latino | % (n/N) | 1.8% (1/56) |
| Not Reported | % (n/N) | 8.9% (5/56) |
| **Race** | | |
| Black | % (n/N) | 53.6% (30/56) |
| White | % (n/N) | 42.9% (24/56) |
| Asian | % (n/N) | 1.8% (1/56) |
| Unknown | % (n/N) | 1.8% (1/56) |

Site reported data.

#### Baseline Medical History

The most common comorbidities among patients include hypertension (89.3%, 50/56), history of smoking (82.1%, 46/56), hypercholesterolemia (37.5%, 21/56), documented coronary artery disease (21.4%, 12/56), gastrointestinal complications (19.6%, 11/56), diabetes mellitus (17.9%, 10/56), and renal insufficiency and previous vascular intervention (each reported in 12.5%, 7/56).

**Table 7: Patient Comorbidities (Pro-D)**

| | Pro-D Patients (N=56) |
| --- | --- |
| **Hypertension (treated or untreated)** | 89.3% (50/56) |
| **History of Smoking** | 82.1% (46/56) |
| Current Smoker | 47.8% (22/46) |
| **Hypercholesterolemia** | 37.5% (21/56) |
| **Current Antiplatelet/Anticoagulant Medication** | 37.5% (21/56) |
| **Documented Coronary Artery Disease** | 21.4% (12/56) |

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**Table 7: Patient Comorbidities (Pro-D)**

| | Pro-D Patients (N=56) |
| --- | --- |
| Stable Angina | 3.6% (2/56) |
| Unstable Angina | 1.8% (1/56) |
| Myocardial Infarction | 3.6% (2/56) |
| Arrhythmias | 1.8% (1/56) |
| Congestive Heart Failure | 5.4% (3/56) |
| Other | 12.5% (7/56) |
| **History of Gastrointestinal Complications** | 19.6% (11/56) |
| Cholecystitis | 0 |
| Ischemic Colitis | 0 |
| GI Bleed | 0 |
| Small Bowel Ischemia | 0 |
| GERD | 12.5% (7/56) |
| Other GI condition | 7.1% (4/56) |
| **Diabetes Mellitus** | 17.9% (10/56) |
| **Renal Insufficiency** | 12.5% (7/56) |
| **History of Vascular Intervention** | 12.5% (7/56) |
| **History of Limb Ischemia** | 8.9% (5/56) |
| **History of Peripheral Vascular Disease** | 7.1% (4/56) |
| **History of Impotence (males only)** | 2.4% (1/41) |

All values expressed as % (n/N). Site reported data.

GERD, gastroesophageal reflux disease; GI, gastrointestinal

#### Baseline Vessel Measurements

The baseline lesion characteristics for the patients enrolled in the study are presented in **Table 8**. All 56 patients had Type B aortic dissection complicated by either malperfusion or rupture. Based on the site’s baseline assessment of the type of dissection, 51.8% (29/56) patients presented with malperfusion of the kidneys, 33.9% (19/56) patients with malperfusion of the viscera, 35.7% (20/56) with malperfusion of the lower extremities, 1.8% (1/56) with malperfusion of the spinal cord, and 10.7% (6/56) with rupture. Sixteen patients (28.6%) had more than one type of malperfusion.

The Core Laboratory reported proximal extent of the dissection in Zone 3 in 78.6% (44/56) of patients, extending distally to the iliac arteries (one or both) in 67.3% (35/52), the abdominal aorta (25.0%, 14/52) or limited to the thoracic aorta (5.4%, 3/52). Mean maximum thoracic aortic diameter is 42.2±6.9 mm (median 40.4 mm, range 27–62.7 mm) and mean aortic diameter at the proximal end of the dissection is 33.8±3.4 mm (median 33.5 mm, range 25–42.1 mm).

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**Table 8: Core Laboratory-Reported Baseline CT Measurements (Pro-D)**

| | Pro-D Patients (N=56) |
| --- | --- |
| **Aortic Diameter at Left Common Carotid (mm)** | |
| n | 55 |
| Mean (SD) | 33.1 (3.3) |
| Median (min, max) | 32.9 (25.1, 41) |
| **Aortic Diameter at Left Subclavian (mm)** | |
| n | 56 |
| Mean (SD) | 33.5 (4.2) |
| Median (min, max) | 32.65 (24.3, 45.2) |
| **Aortic Diameter at Proximal End of Dissection (mm)** | |
| n | 56 |
| Mean (SD) | 33.8 (3.4) |
| Median (min, max) | 33.45 (25, 42.1) |
| **Maximum Thoracic Aortic Diameter (mm)** | |
| n | 56 |
| Mean (SD) | 42.2 (6.9) |
| Median (min, max) | 40.4 (27, 62.7) |
| **Maximum Thoracic Aortic Diameter - True Lumen (mm)** | |
| n | 56 |
| Mean (SD) | 18.6 (7.8) |
| Median (min, max) | 17.8 (3.4, 46.7) |
| **Maximum Thoracic Aortic Diameter - False Lumen (mm)** | |
| n | 56 |
| Mean (SD) | 17.7 (8.9) |
| Median (min, max) | 15.9 (0, 45) |
| **Length from Left Common Carotid to Primary Intimal Tear (mm)** | |
| n | 54 |
| Mean (SD) | 55.7 (48.4) |
| Median (min, max) | 42.2 (5.7, 222) |
| **Length from Left Subclavian to Primary Intimal Tear (mm)** | |
| n | 54 |
| Mean (SD) | 39.6 (47.5) |
| Median (min, max) | 24.7 (-8.37, 198.9) |
| **Total Treatment Length (mm)** | |
| n | 50 |
| Mean (SD) | 207.3 (49.5) |
| Median (min, max) | 214.5 (108, 281) |
| **Dissection Length (mm)** | |
| n | 51 |
| Mean (SD) | 442.1 (104.9) |
| Median (min, max) | 439 (217, 654) |
| **Proximal End of Dissection** | |
| n | 56 |

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**Table 8: Core Laboratory-Reported Baseline CT Measurements (Pro-D)**

| | Pro-D Patients (N=56) |
| --- | --- |
| Zone 1 | 1 (1.8%) |
| Zone 2 | 7 (12.5%) |
| Zone 3 | 44 (78.6%) |
| Zone 4 or further distal | 4 (7.1%) |
| **Distal End of Dissection** | |
| n | 52 |
| Thoracic aorta | 3 (5.4%) |
| Abdominal aorta | 14 (25.0%) |
| Right and left iliacs | 14 (25.0%) |
| Left iliac | 11 (19.6%) |
| Right iliac | 10 (17.9%) |

Core Laboratory data.

#### RelayPro Devices Implanted

A total of 98 RelayPro devices were implanted in the study: 39.3% (22/56) of patients were treated with a single device; 46.4% (26/56) with two; and 14.3% (8/56) with three.

The RelayPro device can be provided in a straight, tapered, and reversed tapered configurations. A device offered in the straight configuration has the same diameter at the proximal and distal ends. A tapered device has a larger proximal diameter than distal diameter, whereas the reverse tapered device has a larger distal diameter than proximal diameter.

Several patients had their treatment extend proximal to the LSA (14.3%, 8/56 with proximal extent of the dissection <Z3; 33/56, 58.9% covering the LSA). The RelayPro NBS was used most often out of all RelayPro devices implanted (65.3%, 64/98).

Additionally, many patients who were treated with more than one device received a combination of NBS and bare stent configurations.

**Table 9: Devices Implanted (Initial Procedure) (Pro-D)**

| | | N=56 | NBS* | Bare Stent* |
| --- | --- | --- | --- | --- |
| **Devices Implanted** | 1 | 39.3% (22/56) | 34.0% (18/53) | 32.1% (17/53) |
| | 2 | 46.4% (26/56) | 37.7% (20/53) | 7.5% (4/53) |
| | 3 | 14.3% (8/56) | 3.8% (2/53) | 3.8% (2/53) |

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**Table 9: Devices Implanted (Initial Procedure) (Pro-D)**

| | N=56 | NBS* | Bare Stent* |
| --- | --- | --- | --- |
| *Total devices implanted** | 98 | 64 | 31 |
| Straight | 91.1% (51/56) | 69.8% (37/53) | 35.8% (19/53) |
| Tapered | 21.4% (12/56) | 11.3% (6/53) | 13.2% (7/53) |

NBS, non-bare stent.

Site reported data. Denominator includes all patients who received the test device. A patient may have received a single NBS and a single bare stent configuration so it is counted as having two devices implanted in total. Therefore, percentages may total more than 100%. In addition, three patients do not have proximal stent configuration specified. Patients with multiple devices implanted may be counted more than once if more than one device shape was used and therefore percentages may sum greater than 100%.

*Many patients in the study who were treated with more than one device received a combination of NBS and bare stent configurations.*

*\*Please note that the device configuration (i.e., NBS or proximal bare stent) for three patients is not known. Therefore, these patients are not included in the denominators for the NBS or bare stent columns.*

The most implanted NBS devices were the 34-mm (22.6%, 12/53), 36-mm (32.1%, 17/53), and 38-mm (17.0%, 9/53) proximal diameters. Regarding the proximal bare stent configuration, the most implanted proximal diameters were the 32-mm (13.2%, 7/53) and 36-mm (18.9%, 10/53) (Table 10). The distal end of the RelayPro proximal bare stent configuration and NBS configuration are identical: the most common distal diameters were 34-mm and 36-mm (each 35.8%, 19/53) and 32 mm (30.2%, 16/53).

**Table 10: Diameter of RelayPro Devices Implanted (Pro-D)**

| Diameter (mm) | | NBS | Proximal Bare Stent |
| --- | --- | --- | --- |
| **Proximal** | 24 | 0 | 0 |
| | 26 | 1.9% (1/53) | 0 |
| | 28 | 7.5% (4/53) | 5.7% (3/53) |
| | 30 | 1.9% (1/53) | 0 |
| | 32 | 15.1% (8/53) | 13.2% (7/53) |
| | 34 | 22.6% (12/53) | 7.5% (4/53) |
| | 36 | 32.1% (17/53) | 18.9% (10/53) |
| | 38 | 17.0% (9/53) | 7.5% (4/53) |
| | 40 | 3.8% (2/53) | 1.9% (1/53) |
| | 42 | 1.9% (1/53) | 1.9% (1/53) |
| | 44 | 0 | 0 |
| | 46 | 0 | 0 |
| **Distal** | 24 | 0 | |
| | 26 | 1.9% (1/53) | |
| | 28 | 11.3% (6/53) | |
| | 30 | 7.5% (4/53) | |
| | 32 | 30.2% (16/53) | |
| | 34 | 35.8% (19/53) | |
| | 36 | 35.8% (19/53) | |

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**Table 10: Diameter of RelayPro Devices Implanted (Pro-D)**

| Diameter (mm) | NBS | Proximal Bare Stent |
| --- | --- | --- |
| 38 | 15.1% (8/53) | |
| 40 | 5.7% (3/53) | |
| 42 | 1.9% (1/53) | |
| 44 | 0 | |
| 46 | 0 | |

NBS, non-bare stent.

*Please note that three patients did not have the device configuration listed (i.e., NBS or proximal bare stent. Each patient only received one RelayPro device (straight configuration). These patients are not included in the denominators.*

### Procedural Data

**Table 11** summarizes information from the index procedure, including clinical utility endpoints. The majority of procedures were percutaneous (85.5%, 47/55). CSF drainage was used in 33.9% (19/56). Median (IQR) total procedure duration was 100 (80-192) min, and the median implantation duration (endovascular part only) was 17 (10-26) min. Postoperatively, patients spent a median 81 (50-142) hours in intensive care. Median overall hospitalization was 7 (5-12) days.

**Table 11: Procedural Details (Pro-D)**

| | Statistics | Pro-D Patients (N=56) |
| --- | --- | --- |
| **Type of Anesthesia** | | |
| General Anesthesia | % (n/N) | 100.0% (56/56) |
| **Vascular Access** | | |
| Left Femoral | % (n/N) | 36.4% (20/55) |
| Right Femoral | % (n/N) | 63.6% (35/55) |
| **Vascular Access Method** | | |
| Percutaneous | % (n/N) | 85.5% (47/55) |
| Surgical Cut Down | % (n/N) | 14.5% (8/55) |
| **CSF Drainage** | % (n/N) | 33.9% (19/56) |
| **Duration of Procedure (min)** | Mean ± SD (N) | 138.4±81.44 (56) |
| | Median (IQR) | 100 (80-192) |
| | Min - Max | 49-429 |
| **Duration of Implantation (min)** | Mean ± SD (N) | 23.9±29.78 (54) |
| | Median (IQR) | 17 (10-26) |
| | Min - Max | 1-180 |
| **Estimated Blood Loss (cc)** | Mean ± SD (N) | 167.2±264.1 (53) |
| | Median (IQR) | 100 (50-150) |
| | Min - Max | 10-1500 |
| **Transfusion required** | % (n/N) | 11.1% (6/54) |
| **Duration of ICU Stay (hours)** | Mean ± SD (N) | 122.5±201.7 (56) |
| | Median (IQR) | 81 (50-142) |
| | Min - Max | 7-1536 |
| **Duration of Hospital Stay (days)** | Mean ± SD (N) | 8.8±4.74 (56) |

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**Table 11: Procedural Details (Pro-D)**

| | Statistics | Pro-D Patients (N=56) |
| --- | --- | --- |
| | Median (IQR) | 7 (5-12) |
| | Min - Max | 2-24 |

Site reported data.

CSF, cerebrospinal fluid; ICU, intensive care unit.

## **D. Safety and Effectiveness Results – Pro-D**

### **1. Safety Results**

#### **1.1 Primary Endpoint**

The primary endpoint is the rate of all-cause mortality at 30-days post procedure and was compared to a performance goal of 25%, which is consistent with other endovascular graft pivotal studies for acute, complicated Type B dissections. The study could stop for success according to the interim analysis plan and based on a sample size of 50 patients (which provides at least 80% power to detect one or more rare adverse events that occur at a population rate of 3.2% or greater) and with a p-value $\leq 0.01317$ to cross the boundary.

The primary endpoint (all-cause mortality at 30-days post procedure) was analyzed with the first 50 patients having completed 30-day follow-up; the result of 2.0% (upper bound of the one-sided 95% CI is 9.1%) was below the 25% performance goal, meaning that the primary endpoint was met (**Table 12**). Further, the calculated p-value met the interim analysis criteria for early stopping for success as the calculated p-value is less than 0.01317.

**Table 12: Primary Endpoint Analysis (Pro-D)**

| Characteristic | Statistics | Pro-D N=50 |
| --- | --- | --- |
| All-cause mortality at 30 days | % (n/N) | 2.0% (1/50) |
| | Upper 95% CI | --, 9.1% |
| | p-value* | <.0001 |

\*P-value corresponds to the null hypothesis test that the observed value is less than the Primary Endpoint. Performance Goal of 25% based on exact upper one-sided 95% CI.

CI, confidence interval.

A per-protocol analysis was not performed as there are no patients that would be removed from the intent-to-treat analysis to do a per-protocol analysis.

There was one patient with all-cause mortality at 30-days. This was a 56-year-old male that presented with a complicated Type B aortic dissection, including malperfusion of the kidneys (site reported), extending 65.4 cm in length. The procedure was performed without complications. The estimated blood loss was 10cc. The patient was discharged POD 7. He was found dead (POD 8). No autopsy was performed and the cause of death is unknown.

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### Supplemental Analysis of Primary Endpoint with full enrollment, N=56

Per study protocol, enrollment continued while 30 day follow-up was being obtained on the initial 50 patients. Six additional patients were treated. A supplemental analysis evaluating the primary analysis using the full study cohort (all 56 patients). The result of 1.8% (upper bound of the one-sided 95% CI is 8.2%) was below the 25% performance goal, also meeting the performance goal (Table 13). For this supplemental analysis, per-protocol analysis was not performed as there are no subjects that would be removed from the intent-to-treat analysis to do a per-protocol analysis.

**Table 13: Primary Endpoint Analysis (Pro-D) Supplemental Analysis**

| Characteristic | Statistics | Pro-D N=56 |
| --- | --- | --- |
| All-cause mortality at 30 days | % (n/N) | 1.8% (1/56) |
| | Upper 95% CI | --, 8.2% |
| | p-value* | <.0001 |

*P-value corresponds to the null hypothesis test that the observed value is less than the Primary Endpoint. Performance Goal of 25% based on exact upper one-sided 95% CI.

CI, confidence interval.

### 1.2 Secondary Safety Endpoints

#### Mortality (All-Cause & Dissection-Related)

Dissection related mortality is death due to a rupture, death within 30 days or of a reintervention to treat the dissection, or death from a complication from the dissection. Dissection related mortality was adjudicated by the CEC. One patient expired POD 8 and met the definition for dissection-related mortality as adjudicated by the CEC as it occurred within 30 days of the index procedure.

There have been nine all-cause mortalities (16.1%, 9/56) (Table 14). There was a single death within 30 days of implant (1.8% dissection-related mortality) and five deaths in total during the total 30-day follow-up window which extends to 90 days (8.9%, 5/56). Subsequently, there was one death in the six-month window (1.9%, 1/52), one in the 12-month window (2.1%, 1/48), two in the 2-year window (5.6%, 2/46), and none thus far in the 3-year or 4-year window.

**Table 14: Mortality (Pro-D)**

| | 30 Days | 6 Months | 12 Months | 2 Years | 3 Years | Total |
| --- | --- | --- | --- | --- | --- | --- |
| Number Eligible | 56 | 52 | 48 | 36 | 18 | 56 |
| **All-Cause Mortality** | | | | | | |
| | 8.9% (5/56) | 1.9% (1/52) | 2.1% (1/48) | 5.6% (2/36) | 0 | 16.1% (9/56) |
| **Dissection-Related Mortality** | | | | | | |
| | 1.8% (1/56) | 0 | 0 | 0 | 0 | 1.8% (1/56) |

All deaths are CEC adjudicated for relatedness to the device and/or procedure. Dissection related mortality was also adjudicated by the CEC.

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Kaplan Meier analysis estimated a freedom from All-Cause Mortality to be 98.1% at 30 days, 87.5% at six months, 85.0% at 12 months, 80.8% at two years, and 75.4% at three years (Figure 3). Kaplan-Meier analysis estimated a freedom from dissection-related mortality of 98.1% at each interval from 30 days to three years (Figure 4).


Figure 3: Kaplan Meier Plot for Freedom from All-Cause Mortality

| POD | # Entered | # Censored | # Events | Event-free (%) | Greenwood SE (%) | 95% CI |
| --- | --- | --- | --- | --- | --- | --- |
| 0 | 56 | 2 | 0 | 100.0% | 0.0% | - |
| 1-30 | 54 | 4 | 1 | 98.1% | 1.9% | 87.4-99.7% |
| 31-180 | 49 | 3 | 5 | 87.5% | 4.8% | 74.3-94.2% |
| 181-360 | 41 | 8 | 1 | 85.0% | 5.2% | 71.0-92.6% |
| 361-540 | 32 | 8 | 0 | 85.0% | 5.2% | 71.0-92.6% |
| 541-720 | 24 | 6 | 1 | 80.8% | 6.5% | 64.0-90.3% |
| 721-900 | 17 | 10 | 1 | 75.4% | 8.0% | 55.5-87.3% |
| CI, confidence interval; POD, postoperative day; SE, standard error. | | | | | | |

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Figure 4: Kaplan-Meier Freedom from Dissection-Related Mortality

| POD | # Entered | # Censored | # Events | Event-free (%) | Greenwood SE (%) | 95% CI |
| --- | --- | --- | --- | --- | --- | --- |
| 0 | 56 | 2 | 0 | 100.0% | 0.0% | - |
| 1-30 | 54 | 4 | 1 | 98.1% | 1.9% | 87.4-99.7% |
| 31-180 | 49 | 7 | 0 | 98.1% | 1.9% | 87.4-99.7% |
| 181-360 | 42 | 10 | 0 | 98.1% | 1.9% | 87.4-99.7% |
| 361-540 | 32 | 8 | 0 | 98.1% | 1.9% | 87.4-99.7% |
| 541-720 | 24 | 7 | 0 | 98.1% | 1.9% | 87.4-99.7% |
| 721-900 | 17 | 11 | 0 | 98.1% | 1.9% | 87.4-99.7% |

CI, confidence interval; POD, postoperative day; SE, standard error.

### Aortic rupture

There have been no Core Laboratory reported aortic or graft ruptures to date. There was one patient with a CEC-adjudicated thoracic aortic rupture in the context of subsequent open surgical thoracoabdominal repair. It is not clear whether the rupture is in the same area that the RelayPro devices were located. Additionally, this observation was not Core Laboratory reported nor was it listed in the clinical notes or imaging studies for this patient.

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# Major Adverse Events

Major adverse events (MAEs) were CEC adjudicated. Seven MAEs were reported in six patients (10.7%), all within 30-days, including the following: paraplegia (n=3), paraparesis (n=2), disabling stroke (n=1), and renal failure (n=1). One patient had two events (renal failure and paraplegia).

Kaplan-Meier analysis estimated a freedom from MAEs of 89.1% at each interval from 30 days to three years (Figure 5).


Figure 5: Kaplan-Meier Freedom from Major Adverse Events (MAEs)

| POD | # Entered | # Censored | # Events | Event-free (%) | Greenwood SE (%) | 95% CI |
| --- | --- | --- | --- | --- | --- | --- |
| 0 | 56 | 0 | 2 | 96.4% | 2.5% | 86.5-99.1% |
| 1-30 | 54 | 7 | 4 | 89.1% | 4.2% | 77.4-95.0% |
| 31-180 | 43 | 5 | 0 | 89.1% | 4.2% | 77.4-95.0% |
| 181-360 | 38 | 10 | 0 | 89.1% | 4.2% | 77.4-95.0% |
| 361-540 | 28 | 6 | 0 | 89.1% | 4.2% | 77.4-95.0% |
| 541-720 | 22 | 6 | 0 | 89.1% | 4.2% | 77.4-95.0% |
| 721-900 | 16 | 11 | 0 | 89.1% | 4.2% | 77.4-95.0% |

CI, confidence interval; POD, postoperative day; SE, standard error.

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**Table 15** presents all MAEs adjudicated by the CEC; once an event is reported it continues to be reported in the “to date” row.

**Table 15: Summary of MAEs (CEC adjudicated) (Pro-D)**

| MAE | 30 Days | 6 Months | 12 Months | 2 Years | 3 Years | Total |
| --- | --- | --- | --- | --- | --- | --- |
| Number Eligible | 56 | 52 | 48 | 36 | 18 | - |
| Patients with ≥1 MAE | 10.7% (6/56) | 0 | 0 | 0 | 0 | 6 |
| MAEs (Total) | 7 | 0 | 0 | 0 | 0 | 7 |
| Stroke (disabling) | | | | | | |
| New | 1 | 0 | 0 | 0 | 0 | - |
| To Date | 1.8% (1/56) | 1.9% (1/53) | 2.0% (1/49) | 2.7% (1/37) | 5.3% (1/19) | 1 |
| Renal Failure | | | | | | |
| New | 1 | 0 | 0 | 0 | 0 | - |
| To Date | 1.8% (1/56) | 1.9% (1/52) | 2.1% (1/48) | 2.8% (1/36) | 5.3% (1/19) | 1 |
| Paraplegia | | | | | | |
| New | 3 | 0 | 0 | 0 | 0 | - |
| To Date | 5.4% (3/56) | 5.7% (3/53) | 6.1% (3/49) | 8.1% (3/37) | 15.0% (3/20) | 3 |
| Paraparesis | | | | | | |
| New | 2 | 0 | 0 | 0 | 0 | - |
| To Date | 3.6% (2/56) | 3.8% (2/52) | 4.2% (2/48) | 5.4% (2/37) | 10.0% (2/20) | 2 |

Note that once an event is reported it continues to show up in the “to date” row in the table.

All MAEs were adjudicated by the CEC using these definitions of the individual MAE components:

- • Stroke (disabling): A sudden, non-convulsive loss of neurological function due to an ischemic or hemorrhagic intracranial vascular event defined as focal neurological deficits that impair the patient’s day-to-day life as assessed by the CEC members, lasting for 365 days or longer.
- • Renal failure: Rise in creatinine >50% above pre-procedure level, resulting in a creatinine level above high normal that does not resolve, and requires prolonged renal replacement therapy
- • Paraplegia: Paralysis of both lower extremities and, generally, lower trunk
- • Paraparesis: Partial paralysis of lower limbs
CEC, clinical events committee; MAE, major adverse event.

### Device-Related Adverse Events

Adverse events adjudicated by the CEC as being device-related are summarized in **Table 16**. This table includes both AEs and SAEs and is sorted by MedDRA SOC and PT: 28.6% (16/56) of patients experienced one or more device-related adverse events with the most frequently reported being stent-graft endoleaks (12 patients; 21.4%) which were coded to the SOC of General Disorders and Administration Site Conditions.

For the 12 patients that have been site-reported as having endoleaks, the Core Laboratory noted false lumen perfusion in 11 patients, namely Type R (7 patients), Type II (2 patients), Type II & Type R (2 patients), and Type Ia & Type R (1 patient). The Case Report Forms (CRFs) for the study did not have a field for reporting false lumen perfusion, resulting in the sites reporting this observation as an endoleak.

The following definitions were utilized for the above Core Laboratory assessment of false lumen perfusion for the 12 patients with a site-reported endoleak:

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- Type Ia entry flow is a perigraft leak at the proximal edge of the stent-graft that allows continued antegrade flow into the false lumen through the primary entry tear.
- Type Ib entry flow is a distal perigraft leak caused by a tear in the intimal membrane adjacent to the distal edge of the endograft (distal stent graft-induced new entry [SINE]).
- Type II entry flow is continued retrograde false lumen perfusion through an arch branch (e.g., left subclavian artery) or intercostal or bronchial artery.
- Type R entry flow is antegrade flow from the true lumen to the false lumen through septal, visceral, or distal fenestrations.

Table 16: Summary of CEC Adjudicated Device-Related Adverse Events (Pro-D)

| MedDRA System-Organ Class Preferred Term Adverse Event | Pro-D Patients (N=56) |
| --- | --- |
| Patients with at least one Device-Related Adverse Event | 16 (28.6%) |
| General disorders and administration site conditions | 11 (19.6%) |
| Complication associated with device | 1 (1.8%) |
| Stent-graft endoleak | 12 (21.4%) |
| Musculoskeletal and connective tissue disorders | 1 (1.8%) |
| Muscular weakness | 1 (1.8%) |
| Nervous system disorders | 3 (5.4%) |
| Paralysis | 1 (1.8%) |
| Paraplegia | 1 (1.8%) |
| Spinal cord ischaemia | 1 (1.8%) |
| Product issues | 1 (1.8%) |
| Device dislocation* | 1 (1.8%) |
| Surgical and medical procedures | 1 (1.8%) |
| Surgery | 1 (1.8%) |
| Vascular disorders | 5 (8.9%) |
| Aortic aneurysm† | 3 (5.4%) |
| Aortic dilatation‡ | 1 (1.8%) |
| Aortic dissection§ | 1 (1.8%) |

Data are presented as n (%). Percentages are based on the number of patients in the Safety Evaluable Population. Event verbatim terms are reported by sites. The events listed in this table are coded using MedDRA version 22.0 and then stratified by System-Organ Class (SOC) and Preferred Term. Patients may be counted in this table more than once by Preferred Term but are only counted once in the SOC summary line. Device Relatedness adjudicated by the CEC.

* One patient had a site reported device dislocation (site reported migration). At the one-year follow-up, the site reported misalignment, migration, and expansion with no endoleak. The Core Laboratory reported Type Ia endoleak and migration due to "dilatation at the proximal end of the device". A secondary intervention (conversion to open surgery) was completed POD 529. ‡ Three patients were reported with device-related aortic aneurysm. One patient had a CEC-adjudicated aortic rupture in the context of subsequent open surgical thoracoabdominal repair. A second patient had an aortic arch aneurysm that was mentioned in the source documentation; however, only in the context of a site reported Type II endoleak and not otherwise detailed. A third patient had aortic lengthening, increased size and opacification of the false lumen that appears to have arisen from a previously coiled LSA, suggestive of a Type II endoleak. This patient was also noted to have aneurysm dilatation of the thoracoabdominal aorta at the diaphragmatic hiatus.

§ Expansion of 5 mm noted by the site at six months. The Core Laboratory reported an increase <5 mm. No intervention was performed. The patient completed four-year follow-up and maximum thoracic aortic diameter has decreased at each follow-up since then the original observation.

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**Table 16: Summary of CEC Adjudicated Device-Related Adverse Events (Pro-D)**

| MedDRA System-Organ Class Preferred Term Adverse Event | Pro-D Patients (N=56) |
| --- | --- |
| 1 Patient was noted on POD 40 to have a tear that appears to have begun at the most proximal aspect of the endovascular graft and involved the aortic arch, as well as the ascending aorta. Core Laboratory analysis confirmed a retrograde dissection. She underwent emergency surgery, where a branched open surgical graft was placed to replace the aortic arch and the ascending aorta. Patient was discharged on POD 44. | |

#### Procedure-Related Adverse Events

Adverse events adjudicated by the CEC as being procedure-related are summarized in **Table 17**. This table includes both AEs and SAEs and is sorted by MedDRA SOC and PT. Eighteen patients (32.1%, 18/56) experienced one or more procedure-related adverse events. The most commonly occurring events were within the MedDRA System-Organ Class of nervous system disorders (16.1%, 9/56):

**Table 17: Summary of CEC Adjudicated Procedure-Related Adverse Events (Pro-D)**

| MedDRA System-Organ Class Preferred Term Adverse Event | Pro-D Patients (N=56) |
| --- | --- |
| Patients with at least one Procedure-Related Adverse Event | 18 (32.1%) |
| **General disorders and administration site conditions** | 5 (8.9%) |
| Death | 1 (1.8%) |
| Stent-graft endoleak | 4 (7.1%) |
| **Investigations** | 1 (1.8%) |
| Pulse absent | 1 (1.8%) |
| **Musculoskeletal and connective tissue disorders** | 2 (3.6%) |
| Compartment syndrome | 1 (1.8%) |
| Muscular weakness | 1 (1.8%) |
| **Nervous system disorders** | 9 (16.1%) |
| Cerebellar infarction | 1 (1.8%) |
| Dysarthria | 1 (1.8%) |
| Embolic stroke | 1 (1.8%) |
| Haemorrhagic transformation stroke | 1 (1.8%) |
| Hemiparesis | 1 (1.8%) |
| Ischaemic stroke | 1 (1.8%) |
| Paralysis | 1 (1.8%) |
| Paraplegia | 1 (1.8%) |
| Spinal cord ischaemia | 2 (3.6%) |
| **Psychiatric disorders** | 1 (1.8%) |
| Delirium | 1 (1.8%) |
| Mental status changes | 1 (1.8%) |
| **Renal and urinary disorders** | 1 (1.8%) |
| Acute kidney injury | 1 (1.8%) |
| **Surgical and medical procedures** | 1 (1.8%) |
| Arterial repair | 1 (1.8%) |
| **Vascular disorders** | 2 (3.6%) |
| Aortic dissection | 1 (1.8%) |
| Poor peripheral circulation | 1 (1.8%) |

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**Table 17: Summary of CEC Adjudicated Procedure-Related Adverse Events (Pro-D)**

| MedDRA System-Organ Class Preferred Term Adverse Event | Pro-D Patients (N=56) |
| --- | --- |

Data are presented as n (%).

Percentages are based on the number of patients in the Safety Evaluable Population.

Event verbatim terms are reported by sites. The events listed in this table are coded using MedDRA version 22.0 and then stratified by System-Organ Class (SOC) and Preferred Term. Patients may be counted in this table more than once by Preferred Term but are only counted once in the SOC summary line.

Procedure Relatedness adjudicated by the CEC.

## 2. Effectiveness Results

### 2.1 Summary of Effectiveness Endpoints

A summary of the secondary endpoints are presented in **Table 18**. Details regarding each of these observations and events (along with other captured information) are presented in the subsequent sections.

**Table 18: Summary of Secondary Endpoints (Pro-D)**

| | 30 Days | 6 Months | 12 Months | 2 Years | 3 Years | Total |
| --- | --- | --- | --- | --- | --- | --- |
| **Treatment Success^{1}** | 85.7% (48/56) | NA | NA | NA | NA | - |
| **Dissection Treatment Success^{2}** | 84.0% (42/50) | 97.0% (32/33) | 93.5% (29/31) | 88.9% (16/18) | 100.0% (7/7) | - |
| **All-Cause Mortality** | 8.9% (5/56) | 1.9% (1/52) | 2.1% (1/48) | 5.6% (2/36) | 0 | 9 |
| **Dissection-Related Mortality** | 1.8% (1/56) | 0 | 0 | 0 | 0 | 1 |
| **Aortic Rupture^{3}** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Type Ia Endoleaks** | 0 | 3.3% (1/30) | 3.3% (1/30) | 0 | 0 | 1 |
| **Type Ib Endoleaks** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Type III Endoleaks** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Loss of Patency** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Kinking** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Twisting** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Misalignment/Birdbeaking** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Loss of Integrity** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Stent fracture** | 0 | 0 | 0 | 0 | 0 | 0 |
| **Migration (>10 mm)** | NA | 3.0% (1/33) | 3.2% (1/31) | 11.1% (2/18) | 0 | 3 |
| **Aortic Expansion (>5 mm)** | NA | 2.9% (1/34) | 6.3% (2/32) | 10.5% (2/19) | 0 | 4 |
| **Secondary Intervention^{4}** | 10.7% (6/56) | 3.8% (2/52) | 8.3% (4/48) | 2.8% (1/36) | 0 | 13 |

1. Treatment success defined as individual components and as a composite:

- a. Absence of major adverse events (stroke, renal failure, paraplegia, paraparesis)
- b. Absence of perfusion into the false lumen through the primary intimal tear;
- c. Absence of retrograde extension of the dissection;

2. Dissection treatment success defined as individual endpoints and as a composite:

- a. Absence of expansion (>5 mm) in the aorta that has an endograft
- b. Absence of aortic rupture;
- c. Absence of dissection-related mortality;
- d. Absence of MAEs including new ischemia due to branch vessel compromise;
- e. Absence of false lumen perfusion separated by location
- f. Absence of new aortobronchial/tracheal or aortoenteric fistula formation;

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**Table 18: Summary of Secondary Endpoints (Pro-D)**

| | 30 Days | 6 Months | 12 Months | 2 Years | 3 Years | Total |
| --- | --- | --- | --- | --- | --- | --- |

g. Absence of unintentional rupture of the dissection septum;
3. Core Laboratory reported rupture
4. Secondary interventions (CEC adjudicated) related to the device or treated pathology.

## 2.2 RelayPro Dissection: Technical Success

Technical Success was assessed by the site investigator at the time of the index procedure is defined as successful delivery and deployment of the device, including withdrawal of the delivery system. Technical success is 100% (56/56) with all primary entry tears covered (56/56, 100%) (Table 19). The stent-graft was reported as accurately deployed and patent, with integrity maintained for all patients. Further, there were no procedures completed related to the inability to withdraw the delivery system.

Although considered a technical success and reported as accurately deployed by the site investigator, one patient had a deployment of the RelayPro device (proximal bare stent configuration) with a twist/kink. During advancement of the inner sheath from the outer sheath, the deployment was noted as stiff and had significant resistance during pullback. The investigator paused the deployment, resulting in the graft falling back approximately 8-10 mm distal of intended landing site (proximal to the LSA as this patient's dissection extended to Z2). The site reported a proximal landing zone of only 13.5 mm, which is possibly why the LSA was covered. There was no patient injury or sequelae as a result of this at time of index procedure nor was there any issues observed on the following day.

Although described as "additional treatment beyond standard of care" (26/56, 46.4%), these procedures were mostly supra-aortic trunk (SAT) revascularizations (33/56, 58.9% of TEVARs were <Z3), which is generally considered standard of care. Also, several patients had LSA coil embolization standardly after SAT revascularization, this was reported as an additional procedure in one patient to correct a Type II endoleak.

Nine patients had additional stents placed during the index procedure (9/56, 16.1%). All additional stents were bare metal stents. Seven patients had stents placed in the visceral or iliac arteries; two patients had stents placed in the aorta. Of the 2 patients with additional stents placed in the aorta, one patient had a bare metal stent overlapping with the distal end of the RelayPro and a second patient had a bare metal stent placed distal to the RelayPro (not overlapping with the RelayPro).

During follow-up, three patients within 30 days; one at two years had a retrograde dissection. Two patients had their observations confirmed by the Core Laboratory.

One patient was reported with vascular access difficulties/complications: this was due to Perclose failure.

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There was no conversion to open repair during the index procedure. A data entry error indicated one patient as a conversion to open repair (noted in the below table). The site confirmed by email (18 Jul 2022) that there had been previous open repair (prior to study participation) and no conversion to open repair as part of this study.

**Table 19: Summary of Technical Success and Procedure-Related Information [Site-Reported] (Pro-D)**

| Device Assessment* | Pro-D Patients (N=56) |
| --- | --- |
| **Technical Success at Index Procedure** | 56 (100.0%) |
| **Evaluation of RelayPro System** | |
| Stent-Graft Deployed | 56 (100.0%) |
| Deployment Without Stent-Graft Kinking or Twisting^{#} | 55 (98.2%) |
| Accuracy of Relay System Deployment Acceptable^{#} | 56 (100.0%) |
| Stent-Graft Patent | 56 (100.0%) |
| Stent-Graft Integrity Maintained (no wire fracture) | 56 (100.0%) |
| Performed Without Unplanned Vascular Access Difficulties or Complications | 55 (98.2%) |
| **Additional Treatment Required Beyond Standard of Care** | 26 (46.4%) |
| LSA Revascularized | 15 (26.8%) |
| Stent Placement^{§} | 9 (16.1%) |
| Other † | 7 (12.5%) |
| Corrected Endoleak †† | 1 (1.8%) |
| Balloon Dilation | 1 (1.8%) |
| **Vascular Access** | |
| Right Femoral | 35 (62.5%) |
| Left Femoral | 20 (35.7%) |
| **Placement of the Proximal End of the Covered Portion of the Device** | |
| Proximal to the LSA | 33 (58.9%) |
| Distal to the LSA | 22 (39.3%) |
| **Final Procedure Result** | |
| Primary Tear Covered | 56 (100.0%) |
| Absence of retrograde extension of the dissection | 48 (85.7%) |
| Conversion to Open Repair ‡ | 1 (1.8%) |
| Other Outcomes § | 3 (5.4%) |

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**Table 19: Summary of Technical Success and Procedure-Related Information [Site-Reported] (Pro-D)**

| Device Assessment* | Pro-D Patients (N=56) |
| --- | --- |

Site reported data. All values expressed as n (%).

*The device assessment was performed at the time of the procedure. (Site reported data.)

† “Other Additional Treatment” comprises: LSA coiling (4 patients); angioplasty balloon mid-external iliac artery (one patient); excised dissection of left SFA (one patient); right femoral artery repair secondary to Perclose failure (one patient).

†† Type II endoleak.

‡ A data entry error indicated one patient a conversion to open repair. The site confirmed by email (18 Jul 2022) that there had been previous open repair and no conversion.

§ “Other outcomes” comprise LLE fasciotomy, restoration of blood flow to right lower extremity, and misalignment at celiac that did not result in any correction, however.

LSA, left subclavian artery.

# See paragraph preceding the table regarding a case that was noted by the site to have accurate deployment; however, the site noted that the device was deployed distally to the intended site.

$ Nine patients had additional stents placed during the index procedure (9/56, 16.1%). All additional stents were bare metal stents. Seven patients had stents placed in the visceral or iliac arteries; two patients had stents placed in the aorta.

### 2.3 Treatment Success at 30 Days

Treatment success through one month, defined as a composite of the following:

- Absence of major adverse events (MAEs), defined as:
- Stroke (disabling)
- Renal failure (excludes pre-existing)
- Paraplegia
- Paraparesis
- Absence of perfusion into the false lumen through the primary intimal tear
- Absence of retrograde extension of the dissection.

Two patients had two events/observations each as summarized in **Table 20**: one patient had renal failure and paraplegia; a second patient had paraparesis and false lumen perfusion through the primary intimal tear.

**Table 20: Treatment Success at 30-Days (Pro-D)**

| | Pro-D Patients (N=56) |
| --- | --- |
| **Treatment Success at 30 days** | 85.7% (48/56) |
| **Freedom from MAEs at 30 days** | 89.3% (50/56) |
| Stroke (disabling) | 1.8% (1/56) |
| Paraplegia | 5.4% (3/56) |
| Paraparesis | 3.6% (2/56) |
| Renal Failure (excluding pre-existing) | 1.8% (1/56) |
| **Absence of false lumen perfusion through the primary intimal tear** | 95.7% (45/47) |
| **Absence of retrograde e…