Valiant Evo International Clinical Trial

Study Overview
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Brief Summary
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The purpose of the Valiant Evo International Clinical Trial is to demonstrate the safety and effectiveness of the Valiant Evo Thoracic Stent Graft System in subjects with a descending thoracic aortic aneurysm (DTAA) who are candidates for endovascular repair.

Detailed Description
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Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort of 100 total subjects, in order obtain 87 evaluable subjects for the primary endpoint. The two protocols are identical, and the trials were run simultaneously to enroll subjects concurrently in the United States (US) and Outside United States (OUS). The poolability on the primary endpoint between US and OUS data will be assessed using Fisher's exact test during the data analysis. Data for both trials will be combined and presented as a pooled analysis.

Official Title
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Valiant Evo International Clinical Trial

Conditions
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Aortic Aneurysm, Thoracic

Intervention / Treatment
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* Device: Valiant Evo Thoracic Stent Graft System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥18 years old Subject understands and voluntarily has signed and dated the Patient Informed Consent approved by the Sponsor and by the Ethics Committee for this study Subject presents a DTAA which is localized below the ostium of left subclavian artery (LSA) and above the ostium of celiac trunk Subject has a DTAA that is one of the following: A fusiform aneurysm with a maximum diameter that: is ≥ 50 mm and/or: is ≥ 2 times the diameter of the non-aneurysmal thoracic aorta and/or: is <50 mm and has grown ≥ 5 mm within previous 12 months A saccular aneurysm or a penetrating atherosclerotic ulcer Subject's anatomy must meet all of the following anatomical criteria as demonstrated on contrast-enhanced CT and/or on contrast-enhanced MRI obtained within four (4) months prior to implant procedure: Proximal and distal non-aneurysmal aortic neck diameter measurements must be ≥ 16 mm and ≤ 42 mm Proximal non-aneurysmal aortic neck length must be ≥ 20 mm (for FreeFlo configuration) and ≥ 25 mm (for Closed Web configuration) Distal non-aneurysmal aortic neck length must be ≥ 20 mm Subject has adequate arterial access site or can tolerate a conduit that allows endovascular access to the aneurysmal site with the delivery system of the appropriate sized device chosen for the treatment. Exclusion Criteria: Subject has a life expectancy of less than 1 year Subject is participating in another investigational drug or device study which would interfere with the endpoints and follow-ups of this study Subject is pregnant Subject requires planned placement of the covered proximal end of the stent graft to occur in zones 0 or 1 Subject has a thoracic aneurysm with a contained rupture or localized at the anastomosis of a previous graft (pseudo-/false aneurysm) Subject has a mycotic aneurysm Subject has a dissection (type A or B) or an intramural hematoma or an aortic rupture in addition to the thoracic aneurysm Subject requires emergent aneurysm treatment, e.g., trauma or rupture Subject has received a previous stent or stent graft or previous surgical repair in the ascending and/or descending thoracic aorta, and/or in the aortic arch Subject requires surgical or endovascular treatment of an infra-renal aneurysm at the time of implant Subject has had previous surgical or endovascular treatment of an infra-renal aortic aneurysm Treatment with the Valiant Evo Thoracic Stent Graft would require intentional revascularization of the brachio-cephalic artery, the left common carotid artery or the celiac trunk Subject has had or plans to have a major surgical or interventional procedure within 30 days before or 30 days after the planned implantation of the Valiant Evo Thoracic Stent Graft. This does not include planned procedures that are needed for the safe and effective placement of the stent graft (i.e., carotid/subclavian transposition, carotid/subclavian bypass procedure) Subject has a significant and/or circumferential aortic mural thrombus at either the proximal or distal attachment sites that could compromise fixation and seal of the implanted stent graft Subject has a connective tissue disease (e.g., Marfan's syndrome, aortic medial degeneration) Subject has a bleeding diathesis or coagulopathy, or refuses blood transfusion. Subject has had a myocardial infarction (MI) within 3 months of the procedure Subject has had a Cerebrovascular Accident (CVA) within 3 months of the procedure Subject has a known allergy or intolerance to the device materials Subject has a known allergy to anesthetic drugs Subject has a known hypersensitivity or contraindication to anticoagulants, or contrast media, which is not amenable to pretreatment Subject has active or systemic infection at the time of the index procedure

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endovascular repair<br>Valiant Evo Thoracic Stent Graft System | Device: Valiant Evo Thoracic Stent Graft System<br>* Procedure: thoracic endovascular aneurysm repair (TEVAR)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Safety and Effectiveness Endpoint That is Based on the Percentage of Subjects Who Experienced (a) Access and/or Deployment Failures; and/or (b) Major Device Effect (MDE) Within 30 Days Post Index Procedure | MDEs include: device-related secondary procedures, device-related mortality, conversion to open surgery, thoracic aortic aneurysm rupture. Access failure: Inability to insert device due to mechanical failure or anatomic exclusions of the femoral or iliac arteries. Deployment failure: Deployment failure due to subject anatomy or mechanical failure. Specifically, deployment of the stent graft from the delivery system. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the primary endpoint global cohort of 87 subjects. The poolability on the primary endpoint between US and OUS data were assessed using Fisher's exact test. | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Effectiveness Outcome | Safety and Effectiveness outcome measures between 0-30 days post implant procedure. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort of 100 subjects (53 US, 47 Outside US [OUS]). Measures include: peri-operative mortality, adverse events (AE), major adverse events (MAE), serious adverse events (SAE), secondary procedures, loss of stent graft patency, and endoleaks. | 30 Days | 
| Safety and Effectiveness Outcome | Safety outcome measures between 0-183 days and Effectiveness outcome measures between 31-183 days post implant procedure. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort. Safety measures include: all-cause mortality (ACM), aneurysm related mortality (ARM), major device effects (MDE), adverse events (AE), major adverse events (MAE), serious adverse events (SAE) and secondary procedures. Effectiveness measures include loss of stent graft patency, endoleaks, stent graft migration as compared to 1-month, and aneurysm expansion greater than 5 mm as compared to 1-month. | 6 Month | 
| Safety and Effectiveness Outcome | Safety outcome measures between 0-365 days and Effectiveness outcome measures between 184-365 days post implant procedure. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort. Safety measures include: all-cause mortality (ACM), aneurysm related mortality (ARM), major device effects (MDE), adverse events (AE), major adverse events (MAE), serious adverse events (SAE) and secondary procedures. Effectiveness measures include loss of stent graft patency, endoleaks, stent graft migration as compared to 1-month, and aneurysm expansion greater than 5 mm as compared to 1-month. | 12 Month | 
| Safety and Effectiveness Outcome | Safety outcome measures between 0-730 days and Effectiveness outcome measures between 366-730 days post implant procedure. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort. Safety measures include: all-cause mortality (ACM), aneurysm related mortality (ARM), major device effects (MDE), adverse events (AE), major adverse events (MAE), serious adverse events (SAE) and secondary procedures. Effectiveness measures include loss of stent graft patency, endoleaks, stent graft migration as compared to 1-month, and aneurysm expansion greater than 5 mm as compared to 1-month. | 24 Month | 
| Safety and Effectiveness Outcome | Safety outcome measures between 0-1095 days and Effectiveness outcome measures between 731-1095 days post implant procedure. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort. Safety measures include: all-cause mortality (ACM), aneurysm related mortality (ARM), major device effects (MDE), adverse events (AE), major adverse events (MAE), serious adverse events (SAE) and secondary procedures. Effectiveness measures include loss of stent graft patency, endoleaks, stent graft migration as compared to 1-month, and aneurysm expansion greater than 5 mm as compared to 1-month. | 36 Month | 
| Safety and Effectiveness Outcome | Safety outcome measures between 0-1460 days and Effectiveness outcome measures between 1096-1460 days post implant procedure. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort. Safety measures include: all-cause mortality (ACM), aneurysm related mortality (ARM), major device effects(MDE), adverse events (AE), major adverse events (MAE), serious adverse events (SAE) and secondary procedures. Effectiveness measures include loss of stent graft patency, endoleaks, stent graft migration as compared to 1-month, and aneurysm expansion greater than 5 mm as compared to 1-month. | 48 month | 
| Safety and Effectiveness Outcome | Safety and Effectiveness outcome measures between implant procedure and 60 months. Data from the Valiant Evo US trial (NCT02652949) and Valiant Evo International trial (NCT02625324) were combined to create the global cohort. Measures include: aneurysm related mortality (ARM), major device effects (MDE), adverse events (AE), major adverse events (MAE), serious adverse events (SAE), secondary procedures, loss of stent graft patency, stent graft migration compared to 1 month imaging, aneurysm expansion greater than 5 mm compared to 1 month imaging, and endoleaks. | 60 Month |