Thoraflex Hybrid
Device Facts
| Record ID | P210006 |
|---|---|
| Device Name | Thoraflex Hybrid |
| Applicant | Vascutek, Ltd. |
| Product Code | QSK · Cardiovascular |
| Decision Date | Apr 19, 2022 |
| Decision | APPR |
| Device Class | Class 3 |
| Attributes | Therapeutic |
Intended Use
The Thoraflex™ Hybrid device is indicated 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.
Device Story
Thoraflex™ Hybrid is a gelatin-coated woven polyester vascular graft combined with a distal self-expanding nitinol stented graft, supplied in a single-use delivery system. Used in open surgical repair (median sternotomy) of aortic arch/descending aorta aneurysms/dissections. The device provides a conduit for blood flow while excluding the lesion. The delivery system allows distal stented graft deployment into the descending aorta while the proximal graft is anastomosed to the native vessel. If additional length is required, the Relay®Pro NBS Thoracic Stent Graft System can be used for distal extension. The device benefits patients by enabling treatment of multi-segment aortic disease in a single open surgical procedure. Surgeons use the device to replace diseased aortic segments, potentially reducing the need for multi-stage procedures. Clinical outcomes are monitored via imaging to assess patency, endoleaks, and aortic size.
Clinical Evidence
Pivotal multi-center, prospective, single-arm study (IDE #G150224) of 65 patients (main arm) and 9 patients (rupture arm). Primary endpoint: 1-year freedom from composite MAEs (permanent stroke, permanent paraplegia/paraparesis, unanticipated aortic-related re-operation, all-cause mortality). Main arm MAE-free rate was 76.9% (95% CI 66.7%–87.2%), meeting the 57.4% performance goal. Secondary endpoints included device technical success (98.5% main arm), treatment success, and incidence of endoleaks, thrombosis, and mortality. Follow-up extended to 3 years.
Technological Characteristics
Implant: Woven polyester graft (gelatin-coated), self-expanding nitinol stents, tantalum radiopaque markers. Delivery system: Malleable stainless-steel shaft, PTFE sheath, atraumatic tip. Energy: None (mechanical). Connectivity: None. Sterilization: 100% Ethylene Oxide (EtO). Standards: ISO 25539-1, ISO 7198, ISO 10993-1.
Indications for Use
Indicated for open surgical repair or replacement of damaged or diseased vessels of the aortic arch and descending aorta, with or without ascending aorta involvement, in cases of aneurysm and/or dissection. Contraindicated in patients with known allergy/intolerance to device materials (polyester, nitinol, tantalum, bovine-origin materials) or conditions threatening to infect the graft.
Regulatory Classification
Identification
Repair or replacement of damaged or diseased vessel of the aortic arch and descending thoracic aorta, with or without involvement of ascending aorta, using vascular grafts and/or stent grafts placed during open surgical repair.
Reference Devices
Related Devices
- P200045 — RelayPro Thoracic Stent-Graft System · Bolton Medical, Inc. · Aug 5, 2021
- P110038 — RELAY THORACIC STENT-GRAFT WITH PLUS DELIVERY SYSTEM · Bolton Medical, Inc. · Sep 21, 2012
- P070007 — TALENT THORACIC STENT GRAFT SYSTEM · Medtronic Vascular · Jun 5, 2008
- P040043 — GORE TAG THORACIC ENDOPROSTHESIS · W. L. Gore & Associates, Inc. · Mar 23, 2005
- P070016 — ZENITH TX2 THORACIC TAA ENDOVASCULAR GRAFT WITH THE H&LB ONE-SHOT INTRODUCTION SYSTEM · William Cook Europe Aps · May 21, 2008
Submission Summary (Full Text)
SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)
I. GENERAL INFORMATION
Device Generic Name: Hybrid stent graft, thoracic aortic lesion treatment
Device Trade Name: Thoraflex™ Hybrid
Device Procode: QSK
Applicant’s Name and Address: Terumo Aortic (Vascutek Ltd)
Newmains Avenue, Inchinnan
Renfrewshire, PA4 9RR
Scotland, UK
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P210006
Date of FDA Notice of Approval: April 19, 2022
Breakthrough Device: Granted breakthrough device status on March 20, 2020 because of reasonable expectation that the device can provide more effective treatment of a life threatening disease; as well has the potential of offering significant advantages over existing cleared alternatives for the 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.
II. INDICATIONS FOR USE
The Thoraflex™ Hybrid device is indicated 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.
III. CONTRAINDICATIONS
The Thoraflex™ Hybrid device is contraindicated in the following;
- Patients with a known allergy or intolerance to device materials (Polyester, Nitinol, tantalum or materials of bovine origin)
- Patients with a condition that threatens to infect the graft
IV. WARNINGS AND PRECAUTIONS
The warnings and precautions can be found in the Thoraflex™ Hybrid labeling.
PMA P210006: FDA Summary of Safety and Effectiveness Data
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V. DEVICE DESCRIPTION
Thoraflex™ Hybrid is designed for the open surgical repair of aneurysms and/or dissections in the aortic arch and descending aorta with or without involvement of the ascending aorta. There are two types of Thoraflex™ Hybrid implants, namely the Plexus 4 and the Ante-Flo versions. Each patient receives one Thoraflex™ Hybrid device (either the Plexus 4 or Ante-Flo). For patients that need additional length for repair of their lesions, the Relay®Pro Non-Bare Stent (NBS) Thoracic Stent Graft System can be used to extend the repair.
**Thoraflex™ Hybrid Device**
The Thoraflex™ Hybrid device is a gelatin coated vascular graft combined with a distal stented graft, supplied pre-loaded in a single use delivery system. The entire implant is coated with gelatin, loaded into a delivery system and terminally sterilized. The Thoraflex™ Hybrid device, once placed in the aorta, provides an alternative conduit for blood flow while excluding the lesion.
**Thoraflex™ Hybrid Implant**
The Thoraflex™ Hybrid implant consists of a proximal vascular graft section, a collar, and a distal stented graft section. Each of these aspects of the implant are described below. The implant is comprised of a woven polyester graft material that is gelatin coated.
The proximal graft section is crimped. The distal stented graft section is comprised of self-expanding nitinol stents sutured to the woven polyester fabric using polyester sutures. The stent scaffold is a series of springs stacked in a tubular configuration. These stents are externally spaced along the length of the graft fabric to provide radial support and allow for the self-expansion of the distal stented graft section. For visualization when extending the Thoraflex™ Hybrid device, there are radiopaque tantalum markers located at approximately 20mm increments starting from the most distal end of the device and covering a total length of 100mm.
The collar is designed to facilitate in the anastomosis of the graft to the native vessel. The anastomosis also provides proximal fixation of the distal stented graft section of the device.
The Thoraflex™ Hybrid device is available in two configurations, which differ only in the proximal vascular graft section, which are the Plexus 4 and Ante-flo versions. The Plexus 4 version (Figure 1) includes three branches for attachment to the great vessels and an ante-flo branch to aid cannulation and perfusion. The Ante-Flo version (Figure 2) contains only a single ante-flo branch.
The Thoraflex™ Hybrid device is tapered between the proximal vascular graft section and the distal stented graft section. For each configuration, the proximal vascular graft section is available in 22 - 32 mm diameters, and the distal stented graft section is available in 24-40 mm diameters. The distal stented section is available in 100 mm and 150 mm lengths. The branches are available in 8 - 12 mm diameters dependent on the graft configuration.
PMA P210006: FDA Summary of Safety and Effectiveness Data
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Figure 1. Thoraflex™ Hybrid Plexus 4 implant
Figure 2. Thoraflex™ Hybrid Ante-Flo implant
PMA P210006: FDA Summary of Safety and Effectiveness Data
# Thoraflex™ Hybrid Delivery System
The Thoraflex™ Hybrid device is supplied pre-loaded in a delivery system (Figure 3) which is designed to facilitate delivery and accurate deployment in the patient's descending aorta. The delivery systems for the Plexus and Ante-Flo configurations are identical. The stented portion of the device is compacted into a PTFE sheath, while the proximal vascular graft section remains largely uncompacted. This allows the distal stented portion to be inserted into the descending aorta while the proximal vascular graft section retains its crimped form. As the device is unsheathed to release the distal stented portion into the descending aorta, the delivery system causes the sheath to split around the proximal vascular graft section to leave it unaffected.
Figure 3. Thoraflex™ Hybrid Delivery System
An atraumatic tip at the distal end of the delivery system has a profile that is designed to guide the delivery system, with or without a guide wire, into the descending aortic arch. The tip has two guide wire ports that can be used at the discretion of the surgeon, depending on the particular anatomy being treated.
The shaft, to which the device is attached via the tip, is comprised of a malleable stainless-steel section that allows the surgeon to manipulate the curvature of the delivery system to treat a particular patient anatomy. The distal stented graft section is attached to the tip of the delivery system via a release wire. The entire graft is also held in place by the splitter, which inhibits rotational and longitudinal movement of the device relative to the delivery system and also assists in splitting the sheath during deployment.
# Extension Device: Relay®Pro NBS Thoracic Stent Graft System
If required, the Thoraflex™ Hybrid device can be extended using a Relay®Pro NBS Thoracic Stent Graft System (P200045). Please refer to the Instructions for Use for a comprehensive device description on this component (P200045). Please also refer to the Thoraflex™ Hybrid Instructions for Use for details on sizing recommendations and other information regarding the use of this device as an extension to the Thoraflex™ Hybrid.
PMA P210006: FDA Summary of Safety and Effectiveness Data
VI. ALTERNATIVE PRACTICES AND PROCEDURES
There are several other alternatives for treatment 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, including medical management, as well as conventional open surgical elephant trunk procedures with an optional second stage open surgical repair. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.
VII. MARKETING HISTORY
Thoraflex™ Hybrid is commercially available in the countries listed in Table 1 below.
Table 1. Thoraflex™ Hybrid Marketing History
| Europe | | | | |
| --- | --- | --- | --- | --- |
| Austria | Denmark | Iceland | Malta | Serbia |
| Belgium | Estonia | Ireland | Netherlands | Slovakia |
| Bosnia | Finland | Italy | Norway | Slovenia |
| Bulgaria | France | Latvia | Poland | Spain |
| Croatia | Germany | Liechtenstein | Portugal | Sweden |
| Cyprus | Greece | Lithuania | Romania | Switzerland |
| Czech Republic | Hungary | Luxembourg | Russia | United Kingdom |
| North America | | | | |
| Canada | Costa Rica | Dominican Republic | Jamaica | Trinidad and Tobago |
| Middle East and Africa | | | | |
| Armenia | Israel | Lebanon | Palestine | Turkey |
| Georgia | Kuwait | Oman | South Africa | United Arab Emirates |
| South America | | | | |
| Brazil | Chile | Colombia | Suriname | |
| Asia-Pacific | | | | |
| Australia | India | Nepal | Singapore | Thailand |
| Hong Kong | Malaysia | New Zealand | Taiwan | Vietnam |
Thoraflex™ Hybrid has not been withdrawn from any market for reasons 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) associated with the use of the device:
PMA P210006: FDA Summary of Safety and Effectiveness Data
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Table 2. Potential Adverse Events
| Anemia | Hepatic failure |
| --- | --- |
| Allergic reaction to polyester / gelatin | Infection of the prosthesis / wound site |
| Aneurysm enlargement | Lymphatic complications e.g. lymph fistula |
| Aneurysm/Lesion Rupture | Multi-system organ failure |
| Aortic damage, including perforation, dissection, bleeding, aortic rupture | Neointimal Hyperplasia |
| Arterial or venous thrombosis | Neurological local or systematic complications e.g. confusion, stroke, transient ischemia attack (TIA), paraplegia, paraparesis, paralysis, spinal cord injury, peripheral neuropathy, altered mental status, temporary post-operative delirium, altered consciousness, coma, new onset seizures |
| Aorto-bronchial fistula, aorto-esophageal fistula, arterial or venous fistula, arteriovenous fistula, Bleeding, blood loss, hematoma, coagulopathy, re-opening, thrombocytopenia, | Prosthesis dilatation |
| Bowel complications e.g. aortoenteric fistula, bowel obstruction, bleeding, infection, ileus, perforation, transient ischemia, infarction, necrosis, mesenteric ischemia, hepatic complications | Pseudoaneurysm |
| Cardiac complications e.g. Angina, arrhythmia (e.g. atrial or ventricular fibrillation) congestive heart failure, hypotension, hypertension shock, cardiac tamponade, valve insufficiency, myocardial infarction, murmur of aortic insufficiency and pulse deficits, embolization (micro and macro) with transient or permanent ischemia or infarction, pericardial effusion, intramural hematoma, occlusion, downstream reintervention for aortic complications | Renal complications e.g. acute kidney injury, renal insufficiency, renal dysfunction, artery occlusion, failure, infarction, transient or permanent increase in serum creatinine, urinary tract infection |
| Device deficiencies e.g. Stented Section: improper component placement; incomplete component deployment; component migration and/or separation; suture break; occlusion; infection; stent fracture; graft material wear; graft twisting/kinking; dilatation; erosion; puncture; perigraft flow; and corrosion | Respiratory complications e.g. breathing difficulties, pneumonia, pulmonary edema, pulmonary embolism, post-operative respiratory insufficiency (defined as requiring prolonged intubation (>72 hours), reintubation, or ventilatory support requiring tracheostomy), pleural effusion, exacerbation of COPD |
PMA P210006: FDA Summary of Safety and Effectiveness Data
| | |
| --- | --- |
| Death | Sepsis |
| Edema | Stenosis |
| Endoleak | Surgical complications: sternal instability, swelling, rash, pain, compartment syndrome, recurrent laryngeal nerve damage/paralysis |
| Fever & localized inflammation | Vascular trauma, spasm, damage and access site complications (infection, pain, hematoma, pseudoaneurysm, arteriovenous fistula, ilio-femoral vessel dissection, bleeding, rupture, deep vein thrombosis) |
| Genitourinary complications e.g. ischemia, erosion, fistula, incontinence, hematuria, infection, impotence | Wound complications e.g. dehiscence, infection, hematoma, seroma, cellulitis, pain, sacral ulcer/pressure sore and any commonly recognized complications associated with the following adverse events: paraplegia/paraparesis, coma and spinal cord injury (for example pressure sores/sacral ulcer resulting from paraplegia) |
For the specific adverse events that occurred in the clinical study, please see Section X below. Long term potential adverse effects will be evaluated in a post approval study.
## IX. SUMMARY OF NONCLINICAL STUDIES
Nonclinical studies were completed to evaluate the Thoraflex™ Hybrid device, including non-clinical bench testing, biocompatibility, sterilization, packaging, shelf-life, and animal studies. These are discussed in detail in the following sections.
### A. Laboratory Studies
Thoraflex™ Hybrid underwent testing for design verification and validation, including long-term durability and corrosion testing. Testing was performed in accordance with international standards and guidance documents, including ISO 25539-1 "Cardiovascular implants -- Endovascular devices -- Part 1: Endovascular prostheses" and ISO 7198 "Cardiovascular implants and extracorporeal systems -- Vascular prostheses -- Tubular vascular grafts and vascular patches." For the evaluation of Thoraflex™ Hybrid, a subset of device components and sizes were used for each test or alternatively, the worst-case configuration/size was selected. The samples selected represented the full size range available for Thoraflex™ Hybrid. Additionally, testing was completed using a Relay®Pro NBS Thoracic Stent Graft System to support the use of this endovascular device as an extension to the Thoraflex™ Hybrid.
PMA P210006: FDA Summary of Safety and Effectiveness Data
A summary of this testing is provided in Table 3. Please note that an asterisk (*) indicates that the testing was performed at baseline and after aging (accelerated or real time to the 2 years shelf life duration).
Table 3. Non-Clinical Testing
| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Design Verification Testing – Thoraflex™ Hybrid Implant | | | |
| Migration Testing | To evaluate the movement (migration) of the device when subjected to variable physiological conditions. This test provides an indication of the resistance to migration provided by the fixation mechanisms of the device (i.e., distal ring). In addition, characterisation pullout testing was completed to evaluate the performance of Thoraflex™ Hybrid against other, commercially available thoracic devices by measuring the tensile force required to remove the device from vessel. | For migration testing, devices should not move more than 10mm during any of the test conditions. Pullout testing was performed for characterization only, therefore there were no set acceptance criteria. | Pass |
| Seal Testing | To verify the sealing ability of the distal stented graft section of Thoraflex™ Hybrid. The test was conducted in a mock (bovine) vessel subjected to physiological conditions. | Thoraflex™ Hybrid leak rate < sutured cleared Gelweave graft (K162794) to vessel leak rate: Leak rate ≤ 130.74 ml/min | Pass |
| Stent to Graft Attachment Force* | To determine the strength of the fixation or attachment system between the distal stent graft material and the nitinol stent rings. | Mean Stent to graft attachment force - 3SD > 38N (Max Loading during deployment) Mean Stent to graft attachment force - 3 SD > 77N (Max loading during compaction) | Pass |
| Flex and Kink Radius | To determine if the device can accommodate worst-case curvature without kinking. | Percentage Reduction in cross-sectional-area at a 101° bend, around 11mm radius < 50%. | Pass |
| Dimensional Verification of Implant | To evaluate the conformance of the Thoraflex™ Hybrid | Stent Diameter THP2224x150: 22.6mm -23.8mm THP3032x150: 30.9mm -32.2mm THP3240x150: 39.4mm - 40.2mm | Pass |
PMA P210006: FDA Summary of Safety and Effectiveness Data
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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | dimensions to their design specifications. | **Device Diameter**
Stented diameter range 24mm – 40mm, in 2mm increments & open vascular graft diameter range 22mm - 32mm | Pass |
| | | **Module Length**
Overall Length = 327-333mm (100mm Devices) or 377- 383mm (150mm Devices)
Unstented Graft (main bore) Length = minimum length of 242mm
Each diameter combination has a nominal 100±5mm (100mmm Devices) and 150±5mm (150mm Devices) stented section. | Pass |
| | | **Collar Width**
12.0mm±2.0mm. | Pass |
| | | **Branch Length**
All branches are a minimum length of 150mm | Pass |
| | | **Branch Inner Diameter**
All Ante-grade perfusion branches are between 9.5-10.5mm inner diameter (ID)
22 and 24mm Plexus grafts have Innominate branches between 9.5-10.5mm ID.
26-32mm Plexus grafts have Innominate branches between 11.0-13.0mm ID
22-32mm Plexus grafts have common Carotid branches between 7.5-8.5mm ID
22 and 24mm Plexus grafts have Left Subclavian branches between 7.5-8.5mm ID.
26-32mm Plexus grafts have Left Subclavian branches between 9.5-10.5mm ID | Pass |
| | | **Branch Spacing**
BP1: 5mm ± 2mm
BP2: 5mm ± 2mm
BP3: 12mm ± 2mm | Pass |
| | | **Radiopaque Marker Positions**
The first marker position is measured from the distal edge of the device to the center of the marker. All other marker positions are measured from center to center.
“M” = Marker
**100mm Devices**
M1: 4.0mm ± 2mm
M2: 20.0mm ± 2mm
M3: 20.0mm ± 2mm
M4: 21.0mm ± 2mm | Pass |
| Test Name | Test Purpose | Acceptance Criteria | | | Results |
| --- | --- | --- | --- | --- | --- |
| | | M5: 19.0mm ± 2mm M6: 19.0mm ± 2mm 150mm Devices M1: 4.0mm ± 2mm M2: 21.5mm ± 2mm M3: 17.5mm ± 2mm M4: 21.0mm ± 2mm M5: 20.0mm ± 2mm M6: 20.0mm ± 2mm | | | |
| Collar Attachment Force | To verify that the tensile strength of the attachment between the collar and proximal vascular graft section is sufficient for this application. | Mean Collar to graft attachment -3SD > 34N | | | Pass |
| Suture Retention Strength | To determine the force required to remove a placed suture from the proximal vascular graft section fabric. | Failure force > 4.5N | | | Pass |
| Blood Leak Testing* | To evaluate the blood leakage from Thoraflex™ Hybrid after compaction and deployment. | Level of blood porosity <21g over the initial 3 minutes | | | Pass |
| Particulate Testing* | To characterise the release of particulates from Thoraflex™ Hybrid devices under simulated use conditions. | The device must not produce excessive levels of particulates during simulated use, defined as: • ≤3 parts/ml ≥25μm • ≤25 parts/ml ≥10μm | | | Pass |
| Whole Graft Porosity | To determine the amount of leakage from the device after the impregnation process, to ensure that it has been sufficiently impregnated, and that excessive leakage will not occur. | <0.15ml/min/cm2 | | | Pass |
| Burst Strength* | To determine the level of applied load at which the fabric of the proximal vascular graft section of the device will burst. | Mean - 3SD > 33.51 N | | | Pass |
| Porosity Testing | To determine the amount of leakage from the raw, ungelled fabric which will be used to produce a Thoraflex™ Hybrid device. | Product Type | Maximum Water Porosity (ml/min/mm2) | | Pass |
| | | | Body | Seam/Black Line | |
| | | Graft section fabric | 515 | 583 | |
| | | Stented section fabric | 346 | 346 | |
PMA P210006: FDA Summary of Safety and Effectiveness Data
| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Relaxed Internal Diameter | To evaluate the conformance of the ThoraflexTM Hybrid dimensions to the design specifications. | All sizes, tolerance ±0.5mm | Pass |
| Longitudinal tensile strength* | To determine the longitudinal tensile failure force of the ThoraflexTM Hybrid device. | Mean Failure force - 3SD > 33.51N | Pass |
| Fatigue and Durability - Computational Analysis | FEA was used to compute the material strains arising within the nitinol stents during manufacture, compaction, deployment and worst-case cyclic radial loading. | FEA simulation results should show a Fatigue Safety Factor >1 when compared with the Fatigue Safety Limit.The FEA study was also used to identify the worst-case prosthesis size for in vitro fatigue testing | Pass |
| Fatigue and Durability - In vitro testing | Pulsatile Fatigue Testing: To evaluate the long-term durability of the stent-graft design over 400 million cycles of pulsatile fatigue loading. | After 100 million and 400 million cycles, the overlapped regions of all test samples shall have:1. No stent fractures such as would affect clinical performance2. No other device integrity failures such as would affect clinical performance. | Pass |
| | Pulsatile Bending Testing: To evaluate the long-term durability of the stent-graft design over 400 million cycles of bending loads. | | Pass |
| Corrosion Testing | To evaluate the corrosion resistance properties of the metallic (all nitinol) components of the ThoraflexTM Hybrid device. | The stent ring components must not be susceptible to failure by localized corrosion under anticipated in-vivo conditions. | Pass |
| Radial Force | To determine the force exerted by the distal stented graft section of the device as a function of the implant diameter, under conditions of compression and extension. The testing was performed not only to obtain results for physical testing, but also to use these results to assess the validity of the current Finite Element Analysis (FEA) model used to extrapolate the rest of the radial force data. | This testing was performed for characterization only.Results from this testing should be comparable to those found by using the finite element analysis model. | Pass |
PMA P210006: FDA Summary of Safety and Effectiveness Data
| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Tray Soaking Verification | To verify that the packaging tray of the Thoraflex™ Hybrid device was capable of allowing the device to be submerged in 700ml of fluid for at least 5 minutes. | A visual inspection will be carried out during and post testing to ensure the device can be fully submerged without the fluid overspilling. This will ensure suitable soaking across the entire device.
If the 700mL of fluid remains within the tray and the device is suitably soaked after 5 minutes, the test can be considered a pass. | Pass |
| **Design Verification Testing – Thoraflex™ Hybrid Delivery System** |
| Dimensional Verification of Delivery System Components* | To ensure that delivery system dimensions are within specification. | **Visual Inspection**
The packaging, tip to sheath interface and the release clips are to be visually inspected to verify they are all intact, as intended and hence acceptable for use | Pass |
| **Overall Length**
Full length (100mm Devices) = 327-333mm
Full length (150mm Devices) = 377-383mm | Pass |
| **Positioning of Splitter**
Tip to Splitter Length (100mm Devices) = 153-159mm
Tip to Splitter Length (150mm Devices) = 203-209mm | Pass |
| **Guide Wire Lumen Diameter**
The guide wire lumen diameters are to be inspected using pin gauges and the lumen should be large enough to allow a 0.035” guide wire to freely pass through it along its full length | Pass |
| **Strap Position and Attachment**
The strap should be on the correct side of the system with all four screws fully engaged | Pass |
| **Splittable PTFE Sheath Inspection**
Sheath Outer Diamter of 10.06mm+0.25mm/-0.10mm
The sheaths should be inspected for any sign of premature splitting. | Pass |
| **Tip Diameter**
The tip diameter should be <45Fr, 15mm | Pass |
| Splitter to Shaft Attachment | To measure the attachment strength of various components of Thoraflex™ Hybrid and ensure they are suitable for the intended application. | Mean Attachment Strength – 3SD > 25.27N | Pass |
| Control Loops to Tip Attachment | Mean Attachment Strength – 3SD > 76N | Pass |
| Device to Delivery System Tensile Testing* | Mean Straight Line Deployment Force + 2SD ≥ 43.65N. | Pass |
| Release Wire to Clip Attachment* | Attachment strength – 3SD ≥ 6.15N | Pass |
PMA P210006: FDA Summary of Safety and Effectiveness Data
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| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Handle to Shaft Compression and Tensile Testing* | | Handle to Shaft Compression - 3SD ≥ 92.12N | Pass |
| Shaft Tension | | Handle to Shaft Tension ≥ 30.17N (Characterization only) | |
| Tin to Shaft Tensile Test* | | Attachment Strength -3SD ≥ 92.12N | Pass |
| Catheter Stop to Shaft Tensile Test* | | Attachment Strength - 3SD ≥ 30.17N | Pass |
| Sheath Splitting Tensile Testing | To verify the delivery system sheath splitting force meets tensile design input requirements. | Sheath Failure Force ≥ 92.12N | Pass |
| Splitter Tensile Testing* | To measure the tensile strength required to open the splitter and to characterise how the splitter failed. | This testing was used for characterization purposes only, as such there was no specific acceptance criteria. | The tensile strength (mean - 3SD) was determined to be 104.87N. |
| Tip to Shaft Torsion Test | To verify that the delivery system tip to shaft and catheter stop to shaft connections meet torsional design input requirements. | Mean Max Torque ≥ 29.22 cNm | Pass |
| Catheter Stop to Shaft Torsion Test | | | |
| Force to Compact* | To evaluate the force required to compact the device into the 28.5F sheath. | Compaction Force Limit is 76N | Pass |
| Deployment Force Testing | To determine the maximum deployment force of the Thoraflex™ Hybrid device. | Sheath retraction force < 97N | Pass |
| Deployment Testing* | To verify the functionality of the Thoraflex™ Hybrid device during deployment into benchtop models of representative anatomy. | The testing would have been deemed to have failed if any aspect of the deployment could not be carried out successfully. | Pass |
| Deployment Accuracy Testing | To assess the accuracy of the deployment position of the Thoraflex™ Hybrid device. | Peaks of the distal ring are placed within ±5mm of the target position after deployment into a model vessel. | Pass |
| Thoraflex™ Hybrid and Relay®Pro NBS Thoracic Stent Graft System Device Extension Testing | | | |
| Integral Water Permeability Testing | To evaluate the amount of leakage between docked Thoraflex™ Hybrid and Relay®Pro NBS Thoracic Stent Graft Systems in both straight and angulated configurations, to ensure a suitable seal is achieved between the | The permeability of the docked Thoraflex™ Hybrid and Relay®Pro NBS Thoracic Stent Graft System must be less than the permeability of the individual devices combined in the same ratio. | Pass |
PMA P210006: FDA Summary of Safety and Effectiveness Data
| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | devices and thus demonstrate that the Relay®Pro NBS Thoracic Stent Graft System is suitable for use as extension devices for Thoraflex™ Hybrid. | | |
| Kink Testing | To determine if the combined Thoraflex™ Hybrid and Relay®Pro NBS Thoracic Stent Graft Systems can accommodate worst-case curvature without kinking. | Percentage Reduction in cross-sectional-area at a 101° bend, around 11mm radius < 50%. | Pass |
| Separation Force Testing | To verify that the force required to separate a Relay®Pro NBS Thoracic Stent Graft System device from a Thoraflex™ Hybrid device is sufficient to withstand the forces experienced in vivo. | The force to separate each Relay®Pro NBS Thoracic Stent Graft System device from the Thoraflex™ Hybrid device shall be ≥ 4N | Pass |
| Distal Ring Dislodgement Testing | To verify that inserting the Relay®Pro NBS Thoracic Stent Graft System delivery system into the Thoraflex™ Hybrid device (in order to deploy the Relay®Pro NBS Thoracic Stent Graft System) will not disturb the distal ring of the Thoraflex™ Hybrid device, in such a way that it prevents the Relay®Pro NBS Thoracic Stent Graft System from docking successfully within the Thoraflex™ Hybrid. | The Relay®Pro NBS Thoracic Stent Graft System delivery system must not disrupt the distal ring of the Thoraflex™ Hybrid such that the Relay®Pro NBS Thoracic Stent Graft System cannot be deployed within the Thoraflex™ Hybrid device with the required 3 z-stent overlap. | Pass |
| Deployment Testing | To deploy a number of Relay®Pro NBS Thoracic Stent Graft Systems into a Thoraflex™ Hybrid device, in order to evaluate the use of the Relay®Pro NBS Thoracic Stent Graft System as an extension device to Thoraflex™ Hybrid, and to ensure there are no additional risks related to the extension procedure which have not been identified and covered in | This testing was used for characterization purposes only, as such there was no specific acceptance criteria. | This characterization testing has determined that the tests performed in the separate verification testing cover all associated risks and design inputs. |
PMA P210006: FDA Summary of Safety and Effectiveness Data
| Test Name | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | the Thoraflex™ Hybrid / Relay®Pro NBS Thoracic Stent Graft System extension verification testing. | | |
| Fatigue and Durability – Computational Analysis | To show the fatigue safety of the Relay®Pro NBS Thoracic Stent Graft System when used at higher oversize for Thoraflex™ Hybrid extension | The worst-case Relay®Pro NBS Thoracic Stent Graft System components should demonstrate a suitable fatigue safety factor of >1.5 for ‘worst case’ and ‘representative’ higher oversizing use, relating to Thoraflex™ Hybrid extension indication as per the IFU. | Pass |
| Fatigue and Durability – in-vitro Testing | Pulsatile Fatigue Testing (Dissection): To evaluate the long-term durability of the Thoraflex™ Hybrid device in a straight, overlapped and dissection configuration with the Relay®Pro NBS Thoracic Stent Graft System over 400 million cycles of pulsatile fatigue loading. | After 100 million and 400 million cycles, the overlapped regions of all test samples shall have: 1. No stent fractures such as would affect clinical performance 2. No other device integrity failures such as would affect clinical performance. | Pass |
| | Pulsatile Bending Testing: To evaluate the long-term durability of the Thoraflex™ Hybrid device in an overlapped, supported static bend configuration with the Relay®Pro NBS Thoracic Stent Graft System over 400 million cycles of bending loads. | | Pass |
| MRI Testing | To provide the recommended scan conditions for use with the device. | Non-clinical testing completed at worst-case conditions for displacement & deflection force, torque force, RF heating, and MRI artifact demonstrated that the Thoraflex™ Hybrid and the Relay®Pro NBS Thoracic Stent Graft System are Magnetic Resonance (MR) Conditional. A patient with these devices can be safely scanned in an MR system meeting the following conditions: Static magnetic field of 3.0 or 1.5 Tesla. Maximum magnetic field spatial gradient of 4,000 gauss/cm (40 T/m). Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 2 W/kg (Normal Operating Mode) | Pass |
PMA P210006: FDA Summary of Safety and Effectiveness Data
# B. Animal Studies
The design of the Thoraflex™ Hybrid device is based on the basic design, materials of construction, and similar processing as other Vascutek devices. Specifically, the proximal vascular graft sections are cleared devices under pre-market notification in the US (K162794). These devices underwent previous animal testing and demonstrated acceptable results with respect to gelatin hydrolysis (if gelatin sealed), device patency, tissue ingrowth, healing response, local and systemic toxicity. Therefore, animal studies from the other Vascutek devices were leveraged in support of the Thoraflex™ Hybrid device. With respect to the other aspects of the device (e.g., stented segment of the implant and delivery system), other available data (e.g., clinical, bench and biocompatibility data) was leveraged to address device safety and performance endpoints typically addressed in stent graft animal studies (e.g., successful deployment, patency).
# C. Biocompatibility
The biocompatibility evaluation of the Thoraflex™ Hybrid device was conducted in accordance with ISO 10993-1:2018 (Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process) and the FDA Guidance Document "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" (2020).
The Thoraflex™ Hybrid device is comprised of an implantable graft with a proximal graft portion and a distal stented graft portion, which is pre-loaded in a delivery system. For purposes of the biocompatibility assessment, the stent graft was classified as an implant device with circulating blood contact and long term exposure ( $>30$ days), while the delivery system was classified as an externally communicating device with tissue/bone/dentin contact and limited exposure ( $\leq 24$ hours). All testing was conducted by a qualified contract laboratory in accordance with FDA GLP regulations, 21 CFR 58.
The Thoraflex™ Hybrid implant successfully met all pre-specified acceptance criteria with the exception of cytotoxicity, mammalian genotoxicity (mouse lymphoma assay), and specific assessments for hemocompatibility (i.e., partial thromboplastin time and complement activation) biocompatibility tests. The results of the biocompatibility testing performed are summarized in Table 4 for the Implant.
Table 4. Biocompatibility Evaluation - Thoraflex™ Hybrid Implant
| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| ISO MTS Cytotoxicity | To determine if cytotoxicity is caused when L-929 mouse fibroblast cells are exposed to implant extracts. | Cytotoxic potential: The neat (100%) and 50% (v/v) dilution extracts had cytotoxic potential. The 25%(v/v) and 12.5% (v/v) dilution extracts had no cytotoxic potential. | No |
| ISO Guinea Pig Maximization Sensitization | To evaluate the allergenic/sensitization potential of implant extracts in guinea pigs. | Non-Sensitizer: All animals scored 0 resulting in 0% sensitization rate. | Yes |
PMA P210006: FDA Summary of Safety and Effectiveness Data
Table 4. Biocompatibility Evaluation – Thoraflex™ Hybrid Implant
| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| | pigs. | | |
| ISO Intracutaneous Reactivity | To evaluate the potential irritation effects after intracutaneous injection of implant extracts in rabbits | Non-irritant: The difference in the overall mean score between the test article extracts and corresponding control was lower than 1.0. | Yes |
| ISO Acute Systemic Toxicity | To evaluate the potential toxic effects after single-dose systemic injections of implant extracts in mice. | There was no mortality or evidence of systemic toxicity from the test article extracts. | Yes |
| ISO Subchronic Toxicity | To evaluate the potential toxic effects after repeated intravenous and intraperitoneal injections of implant extracts in rats over a period of 14-days. | There was no evidence of systemic toxicity from the test article extracts. | Yes |
| Material Mediated Pyrogenicity | To evaluate implant extracts for the potential of inducing a pyrogenic response in rabbits | Non-pyrogenic: Rabbits showed a maximum temperature rise of 0.20, 0.01 and 0.14°C, respectively over a 3-hour period. | Yes |
| Rabbit Intramuscular Implant 90 days | To evaluate local biocompatibility of the components of the Thoraflex™ Hybrid Device in comparison to positive and negative controls via intramuscular implants in the rabbit model. | Components of the Thoraflex™ Hybrid Device did not result in any visible adverse local or distant effects, and no exuberant or unexpected inflammatory or local tissue responses when compared to positive or negative control materials. | Yes |
| Chemical Characterization | To identify and quantify the extractables and/or leachables that may be released from the implant. | Based on the available toxicity data, exposure estimates, and safety margins, the likelihood of extractable chemicals from the implant producing unacceptable carcinogenic or non-carcinogenic health risks in the adult patient population under the proposed conditions and duration of clinical use (long term; >30 days) is acceptable. | Yes |
| Genotoxicity | | | |
| Ames Assay | To evaluate implant extracts for the potential to induce reverse mutations at selected loci of several strains of bacteria. | The implant is considered to be non-mutagenic in the test system | Yes |
PMA P210006: FDA Summary of Safety and Effectiveness Data
Table 4. Biocompatibility Evaluation – Thoraflex™ Hybrid Implant
| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| In vitro Mouse Lymphoma Assay | To evaluate implant extracts for the potential to induce a forward mutation in the TK locus of L5178Y/TK± cells. | The implant is considered to be mutagenic in the test system | No |
| Hemocompatibility | | | |
| Hemolysis | To evaluate the potential of the implant to cause hemolysis in direct contact or by extraction. | Non-hemolytic; Percent hemolysis: Direct contact – 0.0% Extract – 0.0% | Yes |
| Partial Thromboplastin Time (PTT) | To evaluate the potential of the implant extracts to cause an effect on the coagulation cascade via the intrinsic coagulation pathway. | The test article had a final average clotting time of 152.4 seconds and was 55% of the negative control. | No |
| Platelet and Leukocyte Count | To determine if exposure of the implant to human whole blood in vitro will adversely affect the platelet and leukocyte ratios in human whole blood. | The test article results for the leukocyte and platelet counts were 72% and 105%, respectively, of the negative control. The test article normalized platelet value was within 80 to 120% of the negative control. When evaluating the biological significance, the test article normalized platelet value was more than that of the comparison articles (which were all <80% of the negative control). | Yes |
| Complement Activation | To determine the potential of the implant to activate complement. | SC5b-9 – considered to be potential activator of the complement system | No |
A summary of the testing that did not meet the acceptance criteria is provided below:
- Cytotoxicity and genotoxicity: The root cause for the in vitro cytotoxic and genotoxic potential of Thoraflex™ Hybrid was determined to be low level formaldehyde residues (a manufacturing aid, which crosslinks the gelatin sealant). The presence of these residues, which would be expected to yield a positive response in these highly sensitive in vitro tests, has not been related to any observed instances of in vivo effects during biological testing or clinically in patients.
The extractable formaldehyde residue was quantified and evaluated in accordance
PMA P210006: FDA Summary of Safety and Effectiveness Data
with ISO 10993-17:2002 (Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances) and has been determined to be toxicologically acceptable and not impact device safety.
- Hemocompatibility: The Thoraflex™ Hybrid device does not contain novel materials, nor does it contain novel processing, that is dissimilar from other commercially available products, including currently cleared vascular grafts for open procedures. Furthermore, in vivo implantation of Thoraflex™ Hybrid device coupons in rabbit paravertebral muscle for up to 90 days resulted in no visible adverse local or distant effects, and no exuberant or unexpected inflammatory or local tissue responses compared with positive and negative controls. Additionally, the leveraged clinically relevant in vivo animal study performed, also concluded that no systemic or local effects were observed including no evidence of thrombosis in the treated arteries and no evidence of foreign body embolic material in non-graft organs. No instances of Thoraflex™ Hybrid device-related incidences of pseudoaneurysm in the treated segment or anaphylaxis were reported in the US clinical study with 3-year follow-up.
It is concluded that the adverse outcomes observed in the in vitro testing of the Thoraflex™ Hybrid, have not been translated into observable local or distant effects in vivo, and so these aspects of the biological evaluation have been determined to be adequately addressed and the benefits of the device outweigh the potential biocompatibility risks.
The Thoraflex™ Hybrid delivery system successfully met all pre-specified acceptance criteria. The results of the biocompatibility testing performed on the delivery system are summarized in Table 5.
Table 5. Biocompatibility Evaluation – Thoraflex™ Hybrid Delivery System
| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| ISO NRU Cytotoxicity | To determine if delivery system extracts cause cytotoxicity when exposed to L-929 mouse fibroblast cells. | No cytotoxic potential: not considered to have cytotoxic potential. | Yes |
| ISO Guinea Pig Maximization Sensitization | To evaluate the allergenic/sensitization potential of delivery system extracts in guinea pigs. | Non-Sensitizer: All animals scored 0 resulting in 0% sensitization rate | Yes |
| ISO Intracutaneous Reactivity | To evaluate the potential irritation effects after intracutaneous injection of delivery system extracts in rabbits. | Non-irritant: The difference in the overall mean score between the test article extracts and corresponding control was lower than 1.0. | Yes |
| ISO Acute Systemic Toxicity | To evaluate the potential toxic effects after single-dose systemic injections of delivery system extracts in mice. | The test article extracts did not induce a significantly greater biological reaction than the control extracts. | Yes |
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Table 5. Biocompatibility Evaluation – Thoraflex™ Hybrid Delivery System
| Biological Effect (Test) | Purpose | Results | Acceptance Criteria Met? |
| --- | --- | --- | --- |
| Material Mediated Pyrogenicity | To evaluate delivery system extracts for the potential of inducing a pyrogenic response in rabbits. | Non-pyrogenic: Rabbits showed a maximum temperature rise of 0.0, 0.0 and 0.1°C, respectively over a 3-hour period. | Yes |
| Hemocompatibility | | | |
| Hemolysis | To evaluate the potential of the delivery system to cause hemolysis in direct contact or by extraction. | Non-hemolytic; Percent hemolysis: Direct contact – 0.00% Extract – 1.24% | Yes |
D. Sterilization, Packaging and Shelf-Life
Thoraflex™ Hybrid is a single-use device that is provided sterile to the end user. It is sterilized using 100% Ethylene Oxide (EtO) gas with heated aeration to allow for residual EtO dissipation, in accordance with ISO 11135 - Sterilization of health-care products — Ethylene oxide — Requirements for the development, validation and routine control of a sterilization process for medical devices. Devices must have a sterility assurance level (SAL) of 10⁻⁶. Sterilization validation was performed by comparison to "worst case" devices. A total of 72 devices were used, as these have the highest compaction density of all Thoraflex™ Hybrid versions.
Distribution testing has been performed as per ISO 2247:2002 Complete, filled transport packages and unit loads: Vibration tests at fixed low frequency and ISO 22248:1993 Complete, filled transport packages, vertical impact test by dropping.
Packaging validation was executed successfully per AAMI/ANSI/ISO 11607-1:2006: Packaging for terminally sterilized devices – Part 1: Requirements for materials, sterile barrier systems and packaging systems. All packaging and shelf life validation testing was performed as per current standards and Vascutek procedures. The Thoraflex™ Hybrid packaging configuration used in these studies reflects the final package configuration.
Specific engineering testing completed to support shelf life are denoted by an asterisk (*) in Table 3. Accelerated and real time shelf-life product testing conducted on Thoraflex™ Hybrid supports a 2-year shelf-life.
X. SUMMARY OF PRIMARY CLINICAL STUDY
The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the open surgical repair or replacement of aneurysms and/or dissections of the aortic arch and descending aorta with or without involvement of the ascending aorta with the Thoraflex™ Hybrid device in the US under IDE # G150224. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below.
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# A. Study Design
Patients were treated between August 22, 2016 and May 29, 2018. The database for this PMA reflected data collected through July 31, 2021 and included 65 patients in the main study arm and 9 patients in the aortic rupture arm. There were 12 US investigational sites. The study was a multi-center, prospective, single-arm clinical study.
The primary endpoint was defined as the proportion of patients with freedom from the following composite of Major Adverse Events (MAEs) occurring $\leq 1$ year post procedure: permanent stroke (new neurological deficit of abrupt onset caused by a disturbance in blood supply to the brain), permanent paraplegia/paraparesis (complete/partial or incomplete loss of lower limb motor function), unanticipated aortic related re-operation (surgical re-intervention to address complications with the Thoraflex™ Hybrid device excluding reoperation for bleeding), and all-cause mortality.
The results were tested against a performance goal of $57.4\%$, derived from the clinical outcomes (MAEs) after an elephant trunk (ET) procedure collated by two medical centers. These ET MAE frequencies were as follows: $6.5\%$ permanent stroke; $5.4\%$ permanent paraplegia/paraparesis; $28.1\%$ mortality at one year; $2.7\%$ unanticipated aortic related re-operation. The proportion of patients in the historical cohort with 1 or more MAE at one year was $35.7\%$. The proportion of patients MAE-free at one year was $64.3\%$ (95% CI $57.4\%$ to $71.2\%$).
Furthermore, data were extrapolated from a Frozen Elephant Trunk (FET) meta-analysis (Tian et al, 2013) of 17 studies and 1,675 patients (both aneurysm and dissection) that reported $4.9\%$ stroke, $5.1\%$ paraplegia/paraparesis and $15.3\%$ mortality at one year.
Based on these data and assuming a re-operation rate of $2.7\%$, a cumulative total of $28\%$ is achieved. However, as patients often have more than one MAE, this figure was adjusted using the ratio of MAEs per patient observed in the historical cohort (1.2 events per patient), resulting in an overall expected rate of $23.4\%$ of FET patients experiencing one or more MAE. Consequently, it can be expected that $76.6\%$ of patients will be free from MAE. This figure was used together with the performance goal of $57.4\%$ from the historical ET cohort to derive the study sample size.
The hypothesis tested for the primary endpoint at a one-sided alpha level of 0.025 was:
- $\mathrm{H}_{0}: p \leq 0.574$
- $\mathrm{H}_{1}: p > 0.574$
where $p$ represents the probability of being free from the defined composite MAEs in the population under study.
The hypothesis of the primary endpoint was that the 1 year freedom from the defined composite MAEs in the pivotal study was higher than the performance goal of $57.4\%$ in the main study arm. Sample size was calculated assuming that the proportion of patients with freedom from the composite MAEs up to 1-year post-implant was $76.6\%$. Therefore a total of 52 patients would provide $90\%$ power to reject the null hypothesis using a one-
side test and an alpha level of 0.025. To accommodate an anticipated drop-out rate of 20%, 65 patients were enrolled.
External evaluation groups were used during the course of the pivotal study, which are described below:
- Imaging Core Laboratory: An independent core laboratory evaluated all imaging obtained during the course of the study, including endoleak, device migration, aneurysm sac size increase, thrombus in the device and external to the graft, aortic rupture, fistula formation, pseudo-aneurysm, false lumen patency, occlusion, kinking, graft compression, patency of extension device, and stent ring 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 all adverse events reported by the site and classified them as related or not related to the device or the procedure, as well as adverse event outcome. In addition, the CEC adjudicated computated tomography (CT) scan analysis for endoleak, patency and device migration. 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.
- Data Management: A clinical research organization was responsible for data management, safety and medical monitoring and statistics for the study with sponsor oversight.
1. Clinical Inclusion and Exclusion Criteria
Enrollment in the pivotal study was limited to patients who met the following inclusion criteria:
Main Study Arm
A. Acute aortic dissection that required repair or replacement of damaged or diseased vessels of the aortic arch (with or without involvement of the ascending aorta), and the descending aorta requires replacement, or, in the opinion of the investigator, the patient would derive clinical benefit from prophylactic treatment of the descending aorta.
B. Chronic aortic dissection that required repair or replacement of damaged or diseased vessels of the aortic arch and descending aorta with or without involvement of the ascending aorta, with one or more of the following criteria:
- An aortic sinus, or ascending aorta, or aortic arch, or descending aorta diameter ≥5.5 cm (including if asymptomatic), or
- An aortic diameter <5.5 cm and growth rate ≥0.5 cm/year (including if asymptomatic), or
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- An ascending aorta diameter ≥4.5 cm and required valve repair or replacement
C. Aortic aneurysm (including connective tissue disorders) that:
- required repair or replacement of damaged or diseased vessels of the aortic arch and descending aorta with or without involvement of the ascending aorta with one or more of the following criteria:
- An aortic sinus, or ascending aorta, or aortic arch, or descending aorta diameter ≥5.5cm (including if asymptomatic), or
- An aortic diameter <5.5cm and growth rate ≥0.5cm/year (including if asymptomatic), or
- An ascending aorta diameter ≥4.5cm and requires valve repair or replacement, or
- Marfan syndrome or other genetically mediated disorders with aortic sinus, or ascending aorta, or arch diameter ≥4.5cm, or, the ratio of the maximal ascending or aortic root area (Π r2) in cm² divided by the patient’s height in meters exceeds 10
## Rupture Arm
- 18 years or over on the date of consent
- Patient or their legally authorized representative is able and willing to give consent to the patient’s enrollment in the study.
- Either a ruptured thoracic aorta, or, in the experience of the treating surgeon is at high risk of imminent rupture of the thoracic aorta
Patients were not permitted to enroll in the pivotal study if they met any of the following exclusion criteria:
## Main Study Arm
- Unfitness for open surgical repair involving circulatory arrest
- Known sensitivity to polyester, nitinol, or materials of bovine origin
- A ruptured aorta
- Active endocarditis or an active infective disorder of the aorta
- Active systemic infection that, in the opinion of the investigator, would compromise the outcome of the surgical procedure.
- Participation in another active study and has received an investigational product (device, pharmaceutical or biologic) within 6 months prior to the date of the implant or had not reached the primary endpoint of the study
- Pregnant, or planned pregnancy during the course of the study.
- Uncorrectable bleeding anomaly
- Renal failure (defined as dialysis dependent or serum creatinine ≥2.5mg/dL)
- Known sensitivity to radiopaque contrast agents that cannot be adequately pre-treated
- Co-morbidity causing expected survival to be less than 1 year
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- Any other medical, social or psychological problems that in the opinion of the investigator preclude them from study treatment and the procedures and evaluations pre and post procedure
## Rupture Arm
- Chronic dissection or aneurysmal disease which, in the opinion of the investigator, could be treated electively
## 2. Follow-up Schedule
All patients were scheduled to return for follow-up examinations at discharge/30 days, 3 months (13 ± 4 weeks), 12 months (52 ± 8 weeks), and annually through 3 years (± 8 weeks) postoperatively. Adverse events were recorded at all visits.
**Preoperatively** - Each patient was required to have CT imaging with contrast, physical exam, coagulation (PT and APTT), chemistry (BUN & creatinine), and urine or blood human chorionic gonadotropin (hCG) (if applicable).
**At the index procedure** - Each patient was required to be assessed for any required extension procedures/additional unplanned surgical interventions, assessed for any adverse events and device deficiencies and concomitant medications.
**Post-operative follow-up visits** - Assessments during the study included CT with contrast, physical exam, coagulation (PT and APTT), chemistry (BUN & creatinine), patient assessments (HRQoL EQ-5D, return to normal activities), and device deficiencies. If a patient received an extension device, an additional follow-up visit at 3 months after the extension procedure was completed, unless this visit falls within 6 weeks of a visit scheduled as part of the primary follow-up protocol, in which case the additional extension related data was collected at the scheduled primary study visit.
Additional assessments that were collected at each follow-up visit included:
- Adverse events, including
- Serious adverse events
- Non-serious adverse events
- Device-related adverse events
- Procedure-related adverse events
- Aortic-disease related mortality
- Rupture
- Migration
- Endoleak
- Change in aortic size
- Stent graft integrity
- Failed patency
- Secondary procedures
Pre-operative and post-operative parameters measured for all visits are presented in Table 6. Schedule of Activities. The key timepoints are shown below in the tables.
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Table 6. Schedule of Activities
| Assessment (Timing relative to date of implant) | Pre-procedure (≤60 days) | Implant (Day 0) | Discharge or within 30 days^{1} (+/- 7 days) | 3 months (13 ± 4 weeks) | 12 months (52 ± 8 weeks) | 24 months (104 ± 8 weeks) | 36 months (156 ± 8 weeks) | Extension additional follow-up^{2} |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Informed consent | X | | | | | | | |
| Inclusion/ exclusion | X | | | | | | | |
| Demographics and medical history | X^{3} | | | | | | | |
| Physical examination | X^{4} | | X | X | X | X | X | X |
| Vital signs | X | | X | | X | | | X |
| Lab tests (including serum creatinine) as per standard of care | X^{4} | | X | X | X | X | X | |
| Pregnancy test^{5} | X^{4} | | | | | | | |
| Assessment of requirement for extension procedure | X | X | | | | | | |
| Surgical procedural information | | X | | | | | | X |
| Discharge destination | | | X | | | | | |
| CT Imaging | X^{4} | | X^{6} | X | X | X | X | X |
| Additional unplanned surgical interventions | | X | X | X | X | X | X | X |
| Return to normal activities | | | | X | X | X | X | X |
| HRQoL EQ-5D | X^{3} | | X | X | X | X | X | X |
| Concomitant medications | X^{3} | X | X | X | X | X | X | X |
| Adverse events & Device deficiency | | X | X | X | X | X | X | X |
| Extension procedure additional data collection^{7} | | | | | (X) | (X) | (X) | X |
| Study completion^{8} | | | | | | | X | |
1 A follow-up examination was performed at discharge or within 30 days of surgery if the patient remained hospitalized or was unfit for contrast enhanced CT scan at the time of discharge.
2 Additional follow-up visit at 3 months after extension procedures, unless this visit fell within 6 weeks of a visit scheduled as part of the primary follow-up protocol, in which case the additional extension related data was collected at the scheduled primary study visit.
3 For patients recruited to the additional Rupture arm this data could be collected retrospectively
4 For patients recruited to the additional Rupture arm this data could be omitted if collecting the data would delay the patient's treatment and in the opinion of the treating clinician this would increase the patient's risk of death.
5 Women of childbearing potential only, 6hCG test (blood or urine).
6 If patient was not fit for contrast CT scan at time of discharge, then the scan could be performed at a later date up to a maximum of 30 days +/- 7 days after initial surgery.
7 Data only collected for patients who have had an extension procedure.
8 At 3 years post-implant or time of discontinuation.
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# 3. Clinical Endpoints
With regards to safety and effectiveness, the primary endpoint was freedom from the following composite Major Adverse Events (MAEs) occurring $\leq 1$ year post-procedure.
- Permanent stroke
- Permanent paraplegia/paraparesis
- Unanticipated aortic related re-operation (excluding reoperation for bleeding), and
- All-cause mortality
The primary endpoint was compared to a performance goal of $57.4\%$.
With regard to success/failure criteria, the Thoraflex™ Hybrid pivotal study will be considered successful if the lower limit of the $95\%$ confidence interval, associated with the proportion of study patients who are free from the defined composite Major Adverse Events (permanent stroke, permanent paraplegia/paraparesis, unanticipated aortic related reoperation and all-cause mortality) at 1 year post procedure, is greater than $57.4\%$.
The following secondary analyses were completed using descriptive statistics:
## Device Technical Success (at exit from the OR)
- Device technical success is defined as the following:
- Successful delivery and accurate placement of the intraluminal part of the graft at the intended implantation site and retrieval of the device delivery system, and
- Patency of the graft (including branches) and absence of device deformations (e.g., kinks) requiring unplanned placement of additional devices within the graft, and
- No need for unanticipated or emergency surgery (e.g., return to bypass after initial removal of aortic cannula or reversal of heparin) or re-intervention (e.g., placement of additional unplanned endoluminal devices within the frozen segment) related to the device or procedure.
## Procedural Success (at discharge/30 days)
- Procedural success is defined as technical success with absence of the following at discharge/30 days:
- Death
- Major adverse ischemic events: paraplegia / paraparesis, disabling stroke, new ischemia (i.e., not evident at the time of the index procedure) due to branch vessel compromise (malperfusion of organ including bowel, upper limb, or lower limb), distal procedure-related thromboembolic adverse event
- Aortic and valve complications: aortic rupture, Increase in aortic regurgitation grade of greater than 1 (i.e., on 0 – 4 scale)
- General procedure related complications: peri-procedural myocardial infarction (biomarker increase > 10×ULN first 72 hours) or need for urgent or emergent
percutaneous coronary interventions (PCI)/coronary artery bypass grafting (CABG), new onset renal failure requiring dialysis, renal dysfunction or volume overload requiring ultrafiltration, bowel ischemia requiring surgery or intervention, life-threatening bleed, severe Heart Failure (HF) or hypotension requiring pressors or IV inotrope > 24 hr or mechanical circulatory support (MCS), prolonged Intubation > 48 hours, pseudoaneurysm of any graft surgical suture line, additional unplanned surgical or interventional procedures related to the device since completion of the original procedure
## Treatment Success (at discharge/30 days and at all post-procedural intervals)
- Treatment success is defined as device technical success with absence of the following at discharge/30 days and at all post-procedural intervals:
- Aortic enlargement >0.5cm between scheduled post-operative imaging (that is performed within the time windows defined) in the region encompassed by the initial lesion, aortic rupture, fistula formation, lesion-related mortality, loss of device integrity (e.g., wireform fracture that could affect fixation or seal, graft fabric hole or tear, collapse), residual or new Type III endoleak;
- The subset of major adverse events of disabling stroke within 30 days of the procedure and paraplegia/paraparesis (defined as permanent if persisting at 12 months post procedural follow up)
## Individual Patient Success
- Individual patient success is defined as Treatment Success at 12 months, post-operative return to normal activities – employment, household activities, social life, and hobbies, and Improved Health Related Quality of Life Measure (HRQoL) - EQ-5D
## Additional Secondary Endpoints (evaluated at all follow-up intervals unless otherwise noted)
- Incidence of any paraplegia/paraparesis
- Incidence of myocardial infarction
- Incidence of respiratory failure (ventilator dependence greater than 48 hours) at
- Incidence of renal failure requiring dialysis
- Incidence of thromboembolic adverse events as adjudicated by Clinical Events Committee (CEC)
- Incidence of bowel ischemia
- Incidence of failed patency where failed patency was defined as a reduction in blood flow through the device as determined through imaging analysis and requiring surgical intervention.
- Incidence of aortic disease related mortality
- Incidence of all re-interventions in the downstream aorta up to 36 months
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- Incidence of change in aortic size in the grafted segment > 5 mm from the discharge/30 day CT. This was defined as an increase in diameter > 5 mm measured along the major axis. Maximum aortic diameter is measured inner diameter to inner diameter.
- Incidence of pseudo-aneurysm up to 36 months.
- Incidence of aortic rupture up to 36 months. Aortic rupture was defined as leakage of blood from the blood vessel into a body cavity or adjacent organ as determined from imaging.
- Incidence of significant failure of device integrity, up to 36 months, defined as wear or tear in the fabric or wire breakage resulting in a compromised seal and blood leakage or movement of the device.
- Incidence of device migration up to 36 months. Migration was evaluated based on the position of the device at discharge/30 days; migration will be considered as a change > 10 mm from this position. First-stage procedures where the device cannot be adequately placed in the distal landing zone will be reported separately.
- Endoleaks
- Incidence of all endoleaks
- Incidence of secondary procedures to correct endoleaks
- Incidence of thrombosis of the lumen (perigraft lumen, false lumen)
- Endpoints specific to extension procedures:
- Incidence of any failure of device-extension integrity (e.g., wear or tear in the fabric or wire breakage) resulting in a compromised seal and blood leakage or movement of the device
- Incidence of Type III endoleak
- Incidence of failed patency of the device-extension overlap
- Incidence of MAE at 30 days post-extension
- Incidence of secondary procedures related to the extension
- Procedural outcomes which included total operation time, bypass time, blood loss, anesthesia type and time, intraoperative management (i.e. lowest core temperature, spinal drainage), device information and performance, length of ICU stay, length of hospital stay, discharge destination, concomitant procedures)
- Incidence of hypersensitivity reactions up to 36 months
- Post-operative outcomes: return to normal activities – employment, household activities, social life and hobbies and Health Related Quality of Life Measure (HRQoL) - EQ-5D
- Non-serious and serious adverse events
## B. Accountability of PMA Cohort
In the main study arm, 65 patients were implanted with Thoraflex™ Hybrid and seen through discharge.
The primary analysis population for the primary endpoint (freedom from MAE) is the Intent-to-Treat population (ITT) defined as all patients who were enrolled and met all
PMA P210006: FDA Summary of Safety and Effectiveness Data
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selection criteria for the main study arm and treated with the Thoraflex™ Hybrid device. Additional analysis was performed on the Per-Protocol Population defined as all patients enrolled and evaluated for the primary endpoint at one year post-procedure without any major protocol violations.
Table 7 and Table 8 show the patient follow up, imaging adequacy and patient status at each follow up time point for the main and aortic rupture study arm, respectively.
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Table 7. Summary of Visit Compliance and Core Laboratory Imaging Follow-Up: Main Study Arm
| Visit | Patient Follow-Up | | | | | Adequate Imaging to Assess the Parameter† | | | | | Patient Status | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Eligible for Follow-up | Data for Visit | No Visit [1] | Still in Window [2] | CT Scan | Patency | Size Increase | Rupture | Migration | Endoleak | Death | Lost to Follow-up [3] | Early Withdrawal [4] | Not Due for Next Visit [5] |
| Operative | 65 | 65/65 (100%) | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | 0/65 (0.0%) | 0/65 (0.0%) | 0/65 (0.0%) | 0/65 (0.0%) |
| 30 Day | 65 | 65/65 (100%) | 0 | 0/65 (0.0%) | 55/65 (84.6%) | 54/65 (83.0%) | 55/65 (84.6%) | 55/65 (84.6%) | N/A | 54/65 (83.0%) | 5/65 (7.6%) | 2/65 (3.1%) | 1/65 (1.5%) | 0/65 (0.0%) |
| 3 Month | 58 | 58/58 (100%) | 0 | 0/58 (0.0%) | 55/58 (94.8%) | 52/58 (89.6%) | 55/58 (94.8%) | 55/58 (94.8%) | 53/58 (91.3%) | 52/58 (89.6%) | 2/58 (3.4%) | 0/58 0.0%) | 0/58 (0.0%) | 0/58 (0.0%) |
| 1 Year | 56 | 56/56 (100%) | 0 | 0/56 (0.0%) | 54/56 (96.4%) | 52/56 (92.8%) | 54/56 (96.4%) | 54/56 (96.4%) | 53/56 (94.6%) | 52/56 (92.8%) | 4/56 (7.1%) | 3/56 (5.4%) | 3/56 (5.4%) | 0/56 (0.0%) |
| 2 Years | 49 | 49/49 (100%) | 0 | 0/49 (0.0%) | 36/49 (73.5%) | 35/49 (71.4%) | 36/49 (73.5%) | 36/49 (73.5%) | 36/49 (73.5%) | 35/49 (71.4%) | 2/49 (4.1%) | 0/49 (0.0%) | 0/49 (0.0%) | 0/49 (0.0%) |
| 3 Years | 47 | 46/47 (91.5%) | 1 | 0/47 (0.0%) | 33/47 (70.2%) | 30/47 (63.8%) | 33/47 (70.2%) | 33/47 (70.2%) | 33/47 (70.2%) | 30/47 (63.8%) | 0/47 (0.0%) | 0/47 (0.0%) | 0/47 (0.0%) | 0/47 (0.0%) |
| N/A: not applicable; CT: Contrast or non-contrast CT scans. The numbers in the table are the numbers of patients in the specified category. “Data for Visit” means that any data were collected for the follow-up time point. | | | | | | | | | | | | | | |
| [1] Patients who did not have a visit within the window or patients who did not have a visit but have not yet reached the end of the analysis window. | | | | | | | | | | | | | | |
| [2] Patients still within follow-up window, but data not yet available. | | | | | | | | | | | | | | |
| [3] Lost to follow-up includes all Early Withdrawal [4] patients. | | | | | | | | | | | | | | |
| [4] Early withdrawal includes both patient withdrawal and investigator withdrew of patient. | | | | | | | | | | | | | | |
| [5] Not due for next visit includes patients who had visits within the specified window but were not eligible at the start of the next window due to death, surgical conversion, or early withdrawal. | | | | | | | | | | | | | | |
PMA P210006: FDA Summary of Safety and Effectiveness Data
Table 8. Summary of Visit Compliance and Core Laboratory Imaging Follow-Up: Aortic Rupture Arm
| Visit | Patient Follow-Up | | | | | Adequate Imaging to Assess the Parameter† | | | | | Patient Status | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Eligible for Follow-up | Data for Visit | No Visit [1] | Still in Window [2] | CT Scan | Patency | Size Increase | Rupture | Migration | Endoleak | Death | Lost to Follow-up [3] | Early Withdrawal [4] | Not Due for Next Visit [5] |
| Operative | 9 | 9/9 (100%) | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | 0/9 (0.0%) | 0/9 (0.0%) | 0/9 (0.0%) | 0/9 (0.0%) |
| 30 Day | 9 | 9/9 (100%) | 0 | 0/9 (100%) | 6/9 (66.6%) | 6/9 (66.6%) | 6/9 (66.6%) | 6/9 (66.6%) | N/A | 6/9 (66.6%) | 1/9 (11.1%) | 1/9 (11.1%) | 0/9 (0.0%) | 0/9 (0.0%) |
| 3 Month | 7 | 7/7 (100%) | 0 | 0/7 (0.0%) | 5/7 (71.4%) | 5/7 (71.4%) | 5/7 (71.4%) | 5/7 (71.4%) | 5/7 (71.4%) | 5/7 (71.4%) | 0/7 (0.0%) | 1/7 (14.2%) | 0/7 (0.0%) | 0/7 (0.0%) |
| 1 Year | 6 | 6/6 (100%) | 0 | 0/6 (0.0%) | 5/6 (83.3%) | 5/6 (83.3%) | 5/6 (83.3%) | 5/6 (83.3%) | 5/6 (83.3%) | 5/6 (83.3%) | 1/6 (16.6%) | 0/6 (0.0%) | 0/6 (0.0%) | 0/6 (0.0%) |
| 2 Years | 5 | 5/5 (100%) | 0 | 0/5 (0.0%) | 3/5 (60.0%) | 2/5 (40.0%) | 3/5 (60.0%) | 3/5 (60.0%) | 3/5 (60.0%) | 2/5 (40.0%) | 0/5 (0.0%) | 0/5 (0.0%) | 0/5 (0.0%) | 0/5 (0.0%) |
| 3 Years | 4 | 4/4 (100%) | 0 | 0/0 (0.0%) | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 0/4 (0.0%) | 0/4 (0.0%) | 0/4 (0.0%) | 0/4 (0.0%) |
| N/A: not applicable; CT: Contrast or non-contrast CT scans. The numbers in the table are the numbers of patients in the specified category. “Data for Visit” means that any data were collected for the follow-up time point. | | | | | | | | | | | | | | |
| [1] Patients who did not have a visit within the window or patients who did not have a visit but have not yet reached the end of the analysis window. | | | | | | | | | | | | | | |
| [2] Patients still within follow-up window, but data not yet available. | | | | | | | | | | | | | | |
| [3] Lost to follow-up includes Early Withdrawal [4] patients. | | | | | | | | | | | | | | |
| [4] Early withdrawal includes both patient withdrawal and investigator withdrew of patient. | | | | | | | | | | | | | | |
| [5] Not due for next visit includes patients who had visits within the specified window but were not eligible at the start of the next window due to death, surgical conversion, or early withdrawal. | | | | | | | | | | | | | | |
PMA P210006: FDA Summary of Safety and Effectiveness Data
# C. Study Population Demographics and Baseline Parameters
# Demographics and Baseline Characteristics
The demographics of the study population are typical for an aortic arch pathology study performed in the US.
In the main study arm, $66.2\%$ of the patients were male (43/65) and $33.8\%$ were female (22/65). The average age at screening was 64.6 years. The majority of patients in the main study arm were White (44/65, $67.7\%$ ) and non-Hispanic or Latino (87.7%, 57/65) with $43.1\%$ (28/65) of the main study arm being ex-smokers and $40\%$ (26/65) non-smokers.
In the aortic rupture arm, 7 patients $(77.8\%)$ were males and 2 $(22.2\%)$ were females. Patients had an average age of 63.2 years at the time of screening. The majority of patients in the aortic rupture arm were White $(7/9, 77.8\%)$ and $22.2\%$ $(2/9)$ were Hispanic. Five patients $(5/9, 55.9\%)$ were ex-smokers and three $(33.3\%)$ were non-smokers.
The table below summarizes the patient demographics and baseline characteristics for the intent-to-treat population for both the main study arm and aortic rupture arm.
Table 9. Summary of Patient Demographics & Baseline Characteristics (Intent-to-Treat Population)- Overall
| Characteristic | Main Study Arm (N=65) | Aortic Rupture Arm (N=9) |
| --- | --- | --- |
| Gender, n (%) | | |
| Male | 43 (66.2) | 7 (77.8) |
| Female | 22 (33.8) | 2 (22.2) |
| Age at screening | | |
| N | 65 | 9 |
| Mean | 64.6 | 63.2 |
| SD | 12.74 | 16.32 |
| Minimum | 31 | 31 |
| Median | 68.0 | 70.0 |
| Maximum | 86 | 79 |
| Ethnicity, n (%) | | |
| Hispanic or Latino | 5 (7.7) | 2 (22.2) |
| Not Hispanic or Latino | 57 (87.7) | 7 (77.8) |
| Not Reported | 2 (3.1) | 0 (0.0) |
| Unknown | 1 (1.5) | 0 (0.0) |
| Race, n (%) | | |
| Hispanic or Latino | 5 (7.7) | 2 (22.2) |
| Not Hispanic or Latino | 57 (87.7) | 7 (77.8) |
| Not Reported | 2 (3.1) | 0 (0.0) |
| Unknown | 1 (1.5) | 0 (0.0) |
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| Characteristic | Main Study Arm (N=65) | Aortic Rupture Arm (N=9) |
| --- | --- | --- |
| Asian | 6 (9.2) | 0 (0.0) |
| American Indian or Alaska Native | 0 (0.0) | 0 (0.0) |
| Black or African American | 12 (18.5) | 2 (22.2) |
| Native Hawaiian or Other Pacific Islander | 0 (0.0) | 0 (0.0) |
| White | 44 (67.7) | 7 (77.8) |
| Other | 3 (4.6) | 0 (0.0) |
| Baseline Height (cm) | | |
| N | 65 | 9 |
| Mean | 172.6 | 172.54 |
| SD | 10.29 | 6.28 |
| Minimum | 152.40 | 165.10 |
| Median | 172.72 | 170.2 |
| Maximum | 195.6 | 185.4 |
| Baseline Weight (Kg) | | |
| N | 65 | 9 |
| Mean | 86.29 | 81.28 |
| SD | 19.45 | 14.62 |
| Minimum | 50.35 | 60.70 |
| Median | 83.0 | 82.1 |
| Maximum | 142.40 | 99.79 |
| Baseline BMI (kg/m²) | | |
| N | 65 | 9 |
| Mean | 28.85 | 27.32 |
| SD | 5.34 | 4.96 |
| Minimum | 19.9 | 21.0 |
| Median | 28.07 | 26.39 |
| Maximum | 43.3 | 36.1 |
| ASA Grade | | |
| I | 0 (0.0) | 0 (0.0) |
| II | 3 (4.6) | 0 (0.0) |
| III | 7 (10.8) | 1 (11.1) |
| Characteristic | Main Study Arm (N=65) | Aortic Rupture Arm (N=9) |
| --- | --- | --- |
| IV | 55 (84.6) | 7 (77.8) |
| V | 0 (0.0) | 0 (0.0) |
| Missing | 0 (0.0) | 1 (11.1) |
| Smoker | | |
| Yes | 11 (16.9) | 1 (11.1) |
| No | 26 (40.0) | 3 (33.3) |
| Ex-smoker | 28 (43.1) | 5 (55.6) |
| N = Number of patients in the given cohort in the population and is used as the denominator for percentage calculations. n = Number of patients with a value. Baseline is defined as the pre-procedure measurement. BMI = body mass index. | | |
# Baseline Medical and Surgical History
In the main study arm, $92.3\%$ (60/65) had hypertension, $56.9\%$ (37/65) had hyperlipidemia, $38.5\%$ (25/65) had coronary artery disease, $16.9\%$ (11/65) had renal insufficiency, $15.4\%$ (10/65) had chronic obstructive pulmonary disease (COPD), and $13.8\%$ (9/65) had a stroke. The surgical histories for the main study arm include the following: $32.3\%$ (21/65) had a previous aortic dissection repair, $18.5\%$ (12/65) had an aortic valve replacement or repair, $10.8\%$ (7/65) had coronary artery bypass grafting and $10.8\%$ (7/65) had an aortic aneurysm repair.
In the aortic rupture arm, $100\%$ (9/9) had hypertension, $44.4\%$ (4/9) had hyperlipidemia, $22.2\%$ (2/9) had coronary artery disease and $22.2\%$ (2/9) had chronic obstructive pulmonary disease.
Table 10. Summary of Medical & Surgical History (All Enrolled Patients) - Overall
| Category | Main Study Arm (N=65) n (%) | Aortic Rupture Arm (N=9) n (%) |
| --- | --- | --- |
| Cardiac Medical History | | |
| Other | 47 (72.3) | 4 (44.4) |
| Coronary Artery Disease - CAD | 25 (38.5) | 2 (22.2) |
| Congestive Heart Failure - CHF | 10 (15.4) | 1 (11.1) |
| Angina | 3 (4.6) | 0 (0.0) |
| Myocardial Infarction - MI | 5 (7.7) | 1 (11.1) |
| Cardiac Surgical History | | |
| Aortic Dissection Repair | 21 (32.3) | 2 (22.2) |
| Other | 13 (20.0) | 1 (11.1) |
PMA P210006: FDA Summary of Safety and Effectiveness Data
| Category | Main Study Arm (N=65) n (%) | Aortic Rupture Arm (N=9) n (%) |
| --- | --- | --- |
| Aortic Valve Replacement or Repair | 12 (18.5) | 1 (11.1) |
| Aortic Aneurysm Repair | 7 (10.8) | 1 (11.1) |
| Coronary Artery Bypass Graft - CABG | 7 (10.8) | 1 (11.1) |
| Coronary Angioplasty or Stent | 4 (6.2) | 0 (0.0) |
| Pacemaker | 2 (3.1) | 0 (0.0) |
| Endocrine Medical History | | |
| Hypertension | 60 (92.3) | 9 (100.0) |
| Hyperlipidemia | 37 (56.9) | 4 (44.4) |
| Hypothyroid | 9 (13.8) | 1 (11.1) |
| Other | 7 (10.8) | 2 (22.2) |
| Diabetes | 6 (9.2) | 0 (0.0) |
| Cancer | 5 (7.7) | 0 (0.0) |
| Hyperthroid | 1 (1.5) | 0 (0.0) |
| Neurological Medical History | | |
| Other | 10 (15.4) | 0 (0.0) |
| Stroke | 9 (13.8) | 0 (0.0) |
| Transient Ishemic Attack - TIA | 4 (6.2) | 0 (0.0) |
| Seizure | 2 (3.1) | 0 (0.0) |
| Nerve Damage | 1 (1.5) | 0 (0.0) |
| Neuromuscular Disease | 1 (1.5) | 0 (0.0) |
| Paraplegia | 1 (1.5) | 0 (0.0) |
| Pulmonary Medical History | | |
| Other | 27 (41.5) | 3 (33.3) |
| Chronic Obstructive Pulmonary Disease- COPD | 10 (15.4) | 2 (22.2) |
| Asthma | 8 (12.3) | 2 (22.2) |
| Pulmonary Hypertension | 3 (4.6) | 0 (0.0) |
| Emphysema | 2 (3.1) | 0 (0.0) |
| Bronchitis | 1 (1.5) | 0 (0.0) |
| Renal Medical History | | |
| Other | 50 (76.9) | 6 (66.7) |
| Renal Insufficiency | 11 (16.9) | 1 (11.1) |
| Renal Failure | 2 (3.1) | 0 (0.0) |
| Other | 1 (1.5) | 0 (0.0) |
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| Category | Main Study Arm (N=65) n (%) | Aortic Rupture Arm (N=9) n (%) |
| --- | --- | --- |
| Vascular Surgical History | | |
| Endovascular Stent Graft | 5 (7.7) | 1 (11.1) |
| Other | 5 (7.7) | 0 (0.0) |
| Non-Coronary Bypass | 4 (…
