Frailty and Physician Modified Fenestrated Endograft for Thoracoabdominal Aortic Pathologies

Study Overview
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Brief Summary
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The primary objective of this single arm, prospective feasibility study, Impact of Frailty on Clinical Outcomes of Patients Treated for Thoracoabdominal and Complex Abdominal Aortic Aneurysms with Physician-Modified Fenestrated and Branched Stent Grafts, is to assess the use of the physician-modified fenestrated/branched endografts to repair thoracoabdominal and complex aortic aneurysms in subjects having appropriate anatomy, at high risks for open repairs. The primary intent of the study is to assess safety and preliminary effectiveness of the device acutely (i.e., treatment success and technical success), at 30 days (i.e., the rate of major adverse events (MAE)) and at 3 months, 6 months, 12 months, and annually to 5 years (i.e., the proportion of treatment group subjects that achieve and maintain treatment success). Additionally, this study will assess the degree of patient frailty before and after the aneurysm repair, as well as the association between the preoperative baseline frailty and clinical outcomes detailed above. This will help improve subject selection in identification of high risk patients who would not only suffer poor clinical outcomes, but also experience decline in their functional status.

Detailed Description
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Device Description Two types of commercially approved thoracic aortic stent-grafts will be modified under the aegis of a physician-sponsored IDE protocol (G200159). The Cook (Bloomington, IN) Zenith Alpha proximal tapered mainbody thoracic stent-grafts and the Cook Zenith TX2 proximal tapered mainbody will be modified to form the fenestrated/branched aortic components. The Alpha thoracic stent-grafts are constructed of woven polyester graft sewn to discrete rows of self-expanding Nitinol Z stents. The most proximal sealing stent is located internally with fixation barbs that protrude through the graft material. The second proximal stent is straight, and the third stent is tapered by 4mm in diameter. The diameter of the TX2 proximal tapered stent-grafts will range from 32mm to 42mm, depending on the size of the aorta at the proximal seal zone. The lengths will range from 154 to 210mm. The TX2 thoracic stent-grafts are constructed with woven polyester graft sewn to discrete rows of self-expanding stainless steel Z stents. The most proximal seal stent is sewn inside the polyester fabric. The third stent is tapered by either 4mm or 8mm in diameter. The modification design will be planned using a 3-D multiplanar reconstruction analysis of the CT angiography. Proximal seal zone will be chosen at 2cm disease free parallel aortic walls. Target vessel position will be determined by the longitudinal distance between the proximal extent of the seal zone to the middle of the vessel orifice, as well as radial clock position. Based on these measurements, patient specific modification map will be constructed. The modification will be designed to incorporate visceral and renal branches, utilizing a various combinations of fenestrations and branch cuffs. The choice between fenestrations and branch cuffs will be made based on the aortic size and angulation at the level of the target branches. For example, when the target branches are within the seal zone, fenestrations will be chosen. Conversely, branch cuffs will be incorporated onto the mainbody if the aorta at the level of the target branches is aneurysmal, or angulated where precise three dimensional position of the target branch, hence fenestration, along the implanted stent graft is difficult to predict. Modification Technique Modification will be performed on the day of the operation using strict sterile technique. Tapered low profile Cook Zenith Alpha proximal component thoracic stent grafts will be unsheathed. One of the trigger wires is retrieved from the inner cannula of the delivery system, to be used as a diameter constraining wire. This wire is rerouted posteriorly through and through the fabric of the stent graft using a long 22-gauge needle. Fenestrations at planned locations will be created using an ophthalmic cautery, and reinforced with a double layer of Amplatz Gooseneck Snare (Medtronic, Minneapolis, MN) wires made up of braided Nitinol. The wires will be secured around the fenestration by tightly spaced 5-0 Ethibond (Ethicon, Somerville, NJ) locking sutures. Additional radiopaque markers will be sutured around each fenestration. When necessary, directional branch cuffs will be created by fashioning 8mm or 6mm Viabahn self expanding covered stents (Gore & Associates, Flagstaff, AZ) into 2cm long side branch cuffs. The branch cuffs will be sutured to the oval fenestration created on the aortic stent grafts by running 5-0 Goretex sutures. Radiopaque markers will be sutured around the entrance and exit of each branch cuff. Prior to resheathing, the posterior aspect of Z-stents are constrained using loops of prolene sutures as diameter reducing ties. Proximal fixation barbs will be removed using a wire cutter. Fenestrations and branches designed to be catheterized from the brachial approach will be pre-wired with 0.014 inch guidewires. The modified stent graft will be resheathed using 2-0 Silk ties and Umbilical tapes.

Official Title
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Impact of Frailty on Clinical Outcomes of Patients Treated for Thoracoabdominal and Complex Abdominal Aortic Aneurysms With Physician-Modified Fenestrated and Branched Stent Grafts

Conditions
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Thoracoabdominal Aortic Aneurysm, Thoracoabdominal; Aortic, Aneurysm, Dissecting, Pararenal Aneurysm, Frailty Syndrome

Intervention / Treatment
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* Device: Physician Modified Endografts


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients may be included in the study if the patient has at least one of the following indications and are anatomically appropriate for treatment with fenestrated/branched stent grafts. Pararenal, paravisceral, and type I to IV thoracoabdominal aortic aneurysms or chronic post-dissection aneurysms with a diameter 5cm or 2 times the normal aortic diameter. Aneurysm with a history of growth ≥ 0.5cm per year. Saccular aneurysms deemed at significant risk for rupture based on physician interpretation. Symptomatic aneurysm without hemodynamic instability Aneurysms meeting any of the above criteria 1 4, above or below the previous endovascular and/or open aortic repairs. Previously placed aortic stent graft or open aortic grafts may serve as seal zones. Exclusion Criteria: Patients must be excluded from the study if any of the following conditions is true: Less than 18 years of age. Unwilling to comply with the follow-up schedule. Inability or refusal to give informed consent by the patient or a legally authorized representative. Pregnant or breastfeeding. Life-expectancy less than 2 years. Participation in another investigational clinical or device trial, with the exception of participation in another investigational endovascular stent-graft protocol and performed remotely from the fenestrated procedure (>30 days). Examples include remote (>30days) participation in a thoracic, or abdominal branch device trial. Eligible for treatment with FDA-approved marketed device. Eligible and willing to travel to a center with IDE protocol wherein the device is made by a manufacturer.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients may be included in the study if the patient has at least one of the following indications and are anatomically appropriate for treatment with fenestrated/branched stent grafts. Pararenal, paravisceral, and type I to IV thoracoabdominal aortic aneurysms or chronic post-dissection aneurysms with a diameter 5cm or 2 times the normal aortic diameter. Aneurysm with a history of growth ≥ 0.5cm per year. Saccular aneurysms deemed at significant risk for rupture based on physician interpretation. Symptomatic aneurysm without hemodynamic instability Aneurysms meeting any of the above criteria 1 4, above or below the previous endovascular and/or open aortic repairs. Previously placed aortic stent graft or open aortic grafts may serve as seal zones.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PMEG FEVAR<br>The only arm of this study will be enrolled subjects who undergo physician modified endografting as a treatment of their thoracoabdominal aortic aneurysms or complex abdominal aortic aneurysms. | Device: Physician Modified Endografts<br>* Modification procedure Description of modified device is detailed in Section 3.5 of IDE. In summary, the steps involved in modification of the Zenith Alpha thoracic stent grafts are; Unsheathing of the stent graft Retrieval of a trigger wire from the inner cannula of the delivery system Rerouting of the trigger wire along the stent graft Removal of proximal barbs. Creation of fenestrations and/or branch cuffs Placement of radiopaque markers around the fenestrations/ branch cuffs Placement of temporary and/or permanent diameter constraining ties (Optional) Placement of preloaded wires through the fenestrations/branch cuffs<br>* Other names: Fenestrated, Branched Endografts;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Major Adverse Events | Aortic rupture within 30 days Lesion-related mortality within 30 days All-cause mortality within 30 days Permanent paraplegia, defined by lack of resolution at 1 month follow-up Permanent paraparesis, defined by lack of resolution at 1 month follow-up Renal function decline resulting in > 50% of estimated Glomerular Filtration Rate or New onset renal failure requiring dialysis, defined by ongoing dialysis at 1 month follow-up Severe bowel ischemia, requiring laparotomy Disabling stroke, reported within 30 days of the procedure, without resolution at 90 days post-procedure Myocardial infarction Respiratory failure requiring prolonged (> 24 hours from anticipated) mechanical ventilation or reintubation | Immediately after the surgery up to 30 days. If the hospital stay exceeds 30 days, major adverse events that occur prior to discharge from hospital will be included. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Technical Success | Successful delivery of the device(s) to the intended target implantation site(s), and successful removal of the delivery system | Immediately after the surgery | 
| Rate of Treatment Success | Treatment Success is defined by having met ALL of the following dichotomous conditions. Technical success (Yes/No) Absence of death form the initial procedure, secondary intervention for aortic-related cause (Yes/No) Absence of persistent type I or III endoleaks (Yes/No) Absence of aneurysm sac expansion > 5mm (Yes/No) Absence of device migration > 10mm (Yes/No) Absence of failure due to device integrity issues (Yes/No) Absence of aneurysm rupture (Yes/No) Absence of conversion to open surgical repair (Yes/No) Absence of permanent paraplegia, disabling stroke, or dialysis that resulted from the initial operation or a secondary intervention to treat the original aortic pathology (Yes/No) | 30-days, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, 5 years |