Physician-Modified Fenestrated and Branched Aortic Endografting for TAAA

Aortic Aneurysm, Thoracoabdominal Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02989948
• Other study ID #: D18194
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 22, 2020
• Est. completion date: December 31, 2031

Study information

• Verified date: February 2024
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 38
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 95 Years

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Thoracoabdominal

Intervention

Device:
• Physician-modified aortic endograft
Use of physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair.

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
David P. Kuwayama

Country where clinical trial is conducted

United States, 

References & Publications (19)

Browne TF, Hartley D, Purchas S, Rosenberg M, Van Schie G, Lawrence-Brown M. A fenestrated covered suprarenal aortic stent. Eur J Vasc Endovasc Surg. 1999 Nov;18(5):445-9. doi: 10.1053/ejvs.1999.0924. — View Citation

Chuter T, Greenberg RK. Standardized off-the-shelf components for multibranched endovascular repair of thoracoabdominal aortic aneurysms. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):195-201. doi: 10.1177/1531003511430397. — View Citation

Clouse WD, Hallett JW Jr, Schaff HV, Gayari MM, Ilstrup DM, Melton LJ 3rd. Improved prognosis of thoracic aortic aneurysms: a population-based study. JAMA. 1998 Dec 9;280(22):1926-9. doi: 10.1001/jama.280.22.1926. — View Citation

Cowan JA Jr, Dimick JB, Henke PK, Rectenwald J, Stanley JC, Upchurch GR Jr. Epidemiology of aortic aneurysm repair in the United States from 1993 to 2003. Ann N Y Acad Sci. 2006 Nov;1085:1-10. doi: 10.1196/annals.1383.030. — View Citation

Crawford ES, Coselli JS. Thoracoabdominal aneurysm surgery. Semin Thorac Cardiovasc Surg. 1991 Oct;3(4):300-22. No abstract available. — View Citation

Dapunt OE, Galla JD, Sadeghi AM, Lansman SL, Mezrow CK, de Asla RA, Quintana C, Wallenstein S, Ergin AM, Griepp RB. The natural history of thoracic aortic aneurysms. J Thorac Cardiovasc Surg. 1994 May;107(5):1323-32; discussion 1332-3. — View Citation

Greenberg R, Eagleton M, Mastracci T. Branched endografts for thoracoabdominal aneurysms. J Thorac Cardiovasc Surg. 2010 Dec;140(6 Suppl):S171-8. doi: 10.1016/j.jtcvs.2010.07.061. — View Citation

Greenberg RK, Lu Q, Roselli EE, Svensson LG, Moon MC, Hernandez AV, Dowdall J, Cury M, Francis C, Pfaff K, Clair DG, Ouriel K, Lytle BW. Contemporary analysis of descending thoracic and thoracoabdominal aneurysm repair: a comparison of endovascular and open techniques. Circulation. 2008 Aug 19;118(8):808-17. doi: 10.1161/CIRCULATIONAHA.108.769695. Epub 2008 Aug 4. — View Citation

Haulon S, D'Elia P, O'Brien N, Sobocinski J, Perrot C, Lerussi G, Koussa M, Azzaoui R. Endovascular repair of thoracoabdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2010 Feb;39(2):171-8. doi: 10.1016/j.ejvs.2009.11.009. Epub 2009 Nov 27. — View Citation

Kuzmik GA, Sang AX, Elefteriades JA. Natural history of thoracic aortic aneurysms. J Vasc Surg. 2012 Aug;56(2):565-71. doi: 10.1016/j.jvs.2012.04.053. — View Citation

Lee JT, Lee GK, Chandra V, Dalman RL. Comparison of fenestrated endografts and the snorkel/chimney technique. J Vasc Surg. 2014 Oct;60(4):849-56; discussion 856-7. doi: 10.1016/j.jvs.2014.03.255. Epub 2014 Apr 27. — View Citation

Matsumura JS, Melissano G, Cambria RP, Dake MD, Mehta S, Svensson LG, Moore RD; Zenith TX2 Clinical Trial Investigators. Five-year results of thoracic endovascular aortic repair with the Zenith TX2. J Vasc Surg. 2014 Jul;60(1):1-10. doi: 10.1016/j.jvs.2014.01.043. Epub 2014 Mar 14. — View Citation

O'Brien N, Sobocinski J, d'Elia P, Guillou M, Maioli F, Azzaoui R, Haulon S. Fenestrated endovascular repair of type IV thoracoabdominal aneurysms: device design and implantation technique. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):173-7. doi: 10.1177/1531003511408340. Epub 2011 Aug 1. — View Citation

O'Callaghan A, Mastracci TM, Eagleton MJ. Staged endovascular repair of thoracoabdominal aortic aneurysms limits incidence and severity of spinal cord ischemia. J Vasc Surg. 2015 Feb;61(2):347-354.e1. doi: 10.1016/j.jvs.2014.09.011. Epub 2014 Oct 23. — View Citation

Oderich GS, Greenberg RK. Endovascular iliac branch devices for iliac aneurysms. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):166-72. doi: 10.1177/1531003511408344. Epub 2011 Aug 1. — View Citation

Oderich GS, Greenberg RK. The evolving options for endovascular repair of complex aortic aneurysms. Foreword. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):145-8. doi: 10.1177/1531003511407343. No abstract available. — View Citation

Riga CV, McWilliams RG, Cheshire NJ. In situ fenestrations for the aortic arch and visceral segment: advances and challenges. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):161-5. doi: 10.1177/1531003510388421. Epub 2011 Apr 17. — View Citation

Safi HJ, Miller CC 3rd. Spinal cord protection in descending thoracic and thoracoabdominal aortic repair. Ann Thorac Surg. 1999 Jun;67(6):1937-9; discussion 1953-8. doi: 10.1016/s0003-4975(99)00397-5. — View Citation

Starnes BW. Physician-modified endovascular grafts for the treatment of elective, symptomatic, or ruptured juxtarenal aortic aneurysms. J Vasc Surg. 2012 Sep;56(3):601-7. doi: 10.1016/j.jvs.2012.02.011. Epub 2012 May 2. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30 day survival	Percent of patients who survive 30 days following surgery	30 Days
Primary	Major Adverse Events (MAE) at 30 days following surgery	Percent of patients who development major adverse events	30 Days
Primary	Treatment success at 12 months following surgery	Percent of patients achieving treatment success through 1 year	12 Months
Primary	Technical success at 12 months following surgery	Technical success is assessed 12 months following surgery and is defined as a composite of: successful delivery, without need for unanticipated corrective intervention related to delivery; successful and accurate deployment at the intended implantation site; and successful withdrawal, without need for unanticipated correct intervention related to withdrawal.	12 Months
Secondary	Technical success on the day of surgery	Percent of patients achieving technical success on the day of surgery, defined as the composite of; successful delivery, successful and accurate deployment, successful withdrawal.	Day of Surgery
Secondary	Aneurysm rupture	Percent of patients developing aneurysm rupture	Day of Surgery
Secondary	Conversion to open repair	Percent of patients necessitating conversion to open repair. This is assessed intraoperatively. In case of a device deployment failure or intraoperative aneurysm rupture, emergent conversion to open repair via laparotomy, thoracotomy, or thoracoabdominal aortic exposure may become necessary. Patients undergoing such intraoperative conversion will be considered to have met this endpoint.	Day of Surgery
Secondary	Access site complication (Femoral or Iliac)	Percent of patients suffering access site complication (femoral or iliac). If femoral or iliac rupture occurs intraoperatively, or if femoral or iliac flow-limiting dissection or occlusion is identified intraoperatively or on the day of surgery, patients will be considered to have met this outcome.	Day of Surgery
Secondary	Lower extremity ischemia	Percent of patients developing lower extremity ischemia. This will be assess intraoperatively and on the day of surgery. If patients have lower extremity pulses either absent or diminished compared to baseline, with associated pain, sensory deficits or motor deficits on clinical evaluation, patients will be considered to have met this outcome.	Day of Surgery
Secondary	Lower extremity compartment syndrome	Percent of patients developing lower extremity compartment syndrome. In patients with lower extremity pain to passive motion post-operatively, invasive pressure measurement of the four calf compartments will be performed. If compartment pressures are greater than 30 in any compartment, patients will be considered to have met this outcome.	Day of Surgery
Secondary	Stroke	Percent of patients developing stroke - Modified Rankin Score (MRS) of 2 or greater). In patients with altered mental status or lateralizing motor or sensory deficits, MRI of the brain will be performed. If diffusion weighted MRI imaging demonstrates an intracranial lesion, a modified Rankin score will be calculated. If MRS is 2 or greater, patients will be considered to have met this outcome.	Day of Surgery
Secondary	Paraplegia	Percent of patients developing paraplegia. Patients with complete absence of lower extremity motor function in one or both legs will be considered to have met this outcome.	Day of Surgery
Secondary	Paraparesis	Percent of patients developing paraparesis. Patients will undergo lower extremity motor strength assessment post-operatively on a standard 0 to 5 scale. If greater than 0 but less than 5 in either extremity, patients will be considered to have met this outcome.	Day of Surgery
Secondary	Death during surgery	Percent of patients who die during surgery	Day of Surgery
Secondary	Survival rate	Percent of patients who survive	At 30, 183 days; 1, 2, 3, 4 and 5 years
Secondary	Major Adverse Events (MAEs)	Percent of patients that development MAEs	At 30, 183 days; 1, 2, 3, 4 and 5 years
Secondary	Treatment success	Percent of patients achieving treatment success	At 30, 183 days; 2, 3, 4 and 5 years