Physician-Modified Fenestrated and Branched Aortic Endografting for TAAA

Safety and Effectiveness of Physician-Modified Fenestrated and Branched Aortic Endografting for the Treatment of Thoracoabdominal Aortic Aneurysms (TAAA)

The primary clinical objective of this study is to evaluate the safety and effectiveness of a physician-modified, fenestrated and branched aortic endoprosthesis for the treatment of thoracoabdominal aortic aneurysms (TAAAs). The goal of the primary analysis is to demonstrate both the safety and effectiveness of using a physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft as compared to previously published results of open surgical replacement of the aneurysmal aorta.

This study is a prospective, two-arm, traditional feasibility study of a physician modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft base device in adult patients meeting traditional size criteria for open surgical treatment of thoracoabdominal aortic aneurysms (TAAAs). Patients meriting surgical treatment of their aneurysm that also meet inclusion and exclusion criteria will be eligible for enrollment. Patients will be followed for 5 years post procedure. Major adverse events (MAEs) will also be recorded by the Sponsor-Investigator (S-I) and will be monitored by a locally appointed Data Monitoring Committee, Dartmouth-Hitchcock Health and the D-HH Human Research Protection Program IRB/IEC, and the FDA. This record was transferred to Yale in October 2024.

MAIN ARM - Inclusion Criteria:

1. Must be a man or woman 50 years of age or older by the date of informed consent.
2. Must have a thoracoabdominal aortic aneurysm of any Crawford classification (extent I-V) that extends no more proximal than the left subclavian artery.
3. Must have an aneurysm size that meets standard indications for surgical repair (6.0 cm in maximum diameter in the descending thoracic aorta, or 5.5 cm in maximum diameter in the abdominal aorta).
4. Must be considered, in the judgment of the S-I, to be a high risk candidate for open surgical repair.
5. Must not be a candidate for repair under the Instructions for Use of a commercially available, FDA-approved endovascular graft.
6. Must be able to provide informed consent.
7. Must be able to comply with the five year study assessment schedule of events.
8. Must have a non-aneurysm-related life expectancy, in the judgment of the S-I, of greater than 2 years.

MAIN ARM - Exclusion Criteria:

1. Aneurysm due to acute or chronic dissection, intramural hematoma, penetrating aortic ulceration, pseudoaneurysm, mycotic aneurysm, or traumatic transection.

2. Ruptured or acutely symptomatic aortic aneurysm.

3. Known connective tissue disorder.

4. Imaging demonstrating any of the following:

   • Lack of 20 mm non-aneurysmal proximal seal zone (zone 3, or zone 2 with a carotid-subclavian bypass or transposition).
   • Lack of 15 mm non-aneurysmal distal seal zone(s) (aortic, common iliac, or external iliac).
   • Branch vessel target (renal, superior mesenteric, or celiac) < 5 mm or > 10 mm in average diameter.
   • Untreated left subclavian artery stenosis or occlusion.
   • Untreated unilateral or bilateral hypogastric artery occlusion.
   • Signs that the inferior mesenteric artery is indispensable.
   • Have branching, duplication, aneurysm, or untreatable stenosis of the celiac, superior mesenteric artery, or renal arteries that would preclude implantation of the investigational devices.

5. Known sensitivities or allergies to stainless steel, PTFE, polyester, polypropylene, nitinol, or gold.

6. History of anaphylaxis to contrast, with inability to prophylax appropriately.

7. Have uncorrectable coagulopathy.

8. Have unstable angina.

9. Have a body habitus that would inhibit X-ray visualization of the aorta.

10. Have a major surgical or interventional procedure unrelated to the treatment of the aneurysm planned ≤30 days of the endovascular repair.

11. Known to be participating in any other clinical study which may affect performance of this device.

12. Known, visible, or suspected pregnancy, confirmed with a Urine Pregnancy Test (UPT)

13. Contraindication to oral antiplatelet therapy.

14. Prisoners or those on alternative sentencing.

15. Known systemic infection with potential for endovascular graft infection.

16. Anticipated need for MRI scanning within 3 months of insertion of investigational product.

17. Other conditions or comorbidities that, in the opinion of the S-I, would exclude the patient.

EXPANDED ACCESS ARM - Inclusion Criteria

1. Must be a man or woman 50 years of age or older by the date of informed consent
2. Must have a thoracic, thoracoabdominal, or abdominal aortic aneurysm that necessitates coverage of one or more visceral vessels (celiac, superior mesenteric, or renals) for establishment of proximal and/or distal seal.
3. Must have an aneurysm size that meets standard size indications for surgical repair (6.0 cm in maximum diameter in the descending thoracic aorta, or 5.5 cm in maximum diameter in the abdominal aorta); or, in the judgment of the S-I, has aneurysm characteristics that portend a high risk of near-term rupture
4. Must be considered, in the judgement of the S-I, to be a high risk candidate for open surgical repair
5. Must not be a candidate for repair under the Instructions for Use of a commercially available, FDA-approved endovascular graft
6. Patient must be able to provide informed consent
7. Must be able to comply with the five year study assessment schedule of events
8. Must have a non-aneurysm-related life expectancy, in the judgement of the S-I, of greater than 2 years

EXPANDED ACCESS ARM - Exclusion Criteria

1. Known or suspected mycotic aneurysm

2. Ruptured aneurysm with hemodynamic instability

3. Known connective tissue disorder

4. Imaging demonstrating any of the following:

   • Lack of 20 mm non-aneurysmal proximal seal zone (in either native aorta, elephant trunk graft, or aortic arch endograft)
   • Lack of 15 mm non-aneurysmal distal seal zone(s) (in either native aortoiliac vessels, prosthetic aortoiliac grafts, or aortoiliac endografts)
   • Branch vessel target (renal, superior mesenteric, or celiac) > 10 mm in average diameter

5. Known sensitivities or allergies to stainless steel, PTFE, polyester, polypropylene, nitinol, or gold

6. History of anaphylaxis to contrast, with inability to prophylax appropriately.

7. Have uncorrectable coagulopathy

8. Have a body habitus that would inhibit X-ray visualization of the aorta

9. Have a major surgical or interventional procedure unrelated to the treatment of the aneurysm planned ≤ 30 days of the endovascular repair

10. Known to be participating in any other clinical study which may affect performance of this device

11. Known, visible, or suspected pregnancy, confirmed with a Urine Pregnancy Test (UPT)

12. Contraindication to oral antiplatelet therapy

13. Prisoners or those on alternative sentencing

14. Known systemic infection with potential for endovascular graft infection

15. Anticipated need for MRI scanning within 3 months of insertion of investigational product

16. Other conditions or comorbidities that, in the opinion of the S-I, would exclude the patient