Clinical Study of the BARD® COVERA™ Arteriovenous (AV) Stent Graft

Study Overview
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Brief Summary
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The objective of this study is to assess the safety and effectiveness of the COVERA™ Vascular Covered Stent for the treatment of stenotic lesions in the upper extremity venous outflow of the Arteriovenous (AV) access circuit.

Detailed Description
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This study will compare the use of the COVERA™ Vascular Covered Stent (following percutaneous transluminal angioplasty (PTA)) to PTA alone for the treatment of stenotic lesions in the upper extremity venous outflow of the arteriovenous (AV) access circuit of subjects dialyzing with an AV fistula.

Official Title
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A Prospective, Multi-Center, Randomized, Concurrently-Controlled Clinical Study of the BARD® COVERA™ Arteriovenous (AV) Stent Graft in the Treatment of Stenosis in the Venous Outflow of AV Fistula Access Circuits (AVeNEW)

Conditions
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Stenosis, Restenosis

Intervention / Treatment
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* Device: Covera Vascular Covered Stent following PTA
* Procedure: Percutaneous Transluminal Angioplasty (PTA) with Uncoated PTA Balloon


Participation Criteria
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Eligibility Criteria
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Clinical Inclusion Criteria: Subject must voluntarily sign and date the Informed Consent Form (ICF) prior to collection of study data or performance of study procedures. Subject must be either a male or non-pregnant female ≥ 21 years of age with an expected lifespan sufficient to allow for completion of all study procedures. Subject must be willing to comply with the protocol requirements, including the clinical and telephone follow-up. Subject must have an upper extremity arteriovenous (AV) fistula that has undergone at least one successful dialysis session with two-needle cannulation, prior to the index procedure. Angiographic Inclusion Criteria: Subject must have angiographic evidence of a stenosis ≥ 50% (by visual estimation) located in the venous outflow of the AV access circuit and present with clinical or hemodynamic evidence of AV fistula dysfunction. The target lesion must be ≤ 9cm in length. Note: multiple stenoses may exist within the target lesion. The reference vessel diameter of the adjacent non-stenotic vein must be between 5.0 and 9.0mm. Clinical Exclusion Criteria: The subject is dialyzing with an AV graft. The target lesion has had a corresponding thrombosis treated within 7 days prior to the index procedure. The hemodialysis access is located in the lower extremity. The subject has an infected AV fistula or uncontrolled systemic infection. The subject has a known uncontrolled blood coagulation/bleeding disorder. The subject has a known allergy or hypersensitivity to contrast media which cannot be adequately pre-medicated. The subject has a known hypersensitivity to nickel-titanium (Nitinol) or tantalum. The subject has another medical condition, which, in the opinion of the Investigator, may cause him/her to be non-compliant with the protocol, confound the data interpretation, or is associated with a life expectancy insufficient to allow for the completion of study procedures and follow-up. The subject is currently participating in an investigational drug or another device study that has not completed the study treatment or that clinically interferes with the study endpoints. Note: Studies requiring extended follow-up visits for products that were investigational, but have since become commercially available, are not considered investigational studies. Angiographic Exclusion Criteria: Additional stenotic lesions (≥ 50%) in the venous outflow that are > 3cm from the edge of the target lesion and are not successfully treated (defined as < 30% residual stenosis) prior to treating the target lesion. An aneurysm or pseudoaneurysm is present within the target lesion. The location of the target lesion would require the COVERA™ Vascular Covered Stent be deployed across the elbow joint. The target lesion is located within a stent. The location of the target lesion would require that the COVERA™ Vascular Covered Stent be deployed at or across the segment of fistula utilized for dialysis needle puncture (i.e., cannulation zone). The location of the target lesion would require that the COVERA™ Vascular Covered Stent be placed in the central veins (subclavian, brachiocephalic, superior vena cava (SVC)) or under the clavicle at the thoracic outlet. There is incomplete expansion of an appropriately sized angioplasty balloon to its expected profile, in the operator's judgment, during primary angioplasty at the target lesion prior to randomization.

Ages Eligible for Study
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Minimum Age: 21 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Covera Vascular Covered Stent following PTA<br>Placement of the Covera Vascular Covered Stent following percutaneous transluminal angioplasty (PTA) | Device: Covera Vascular Covered Stent following PTA<br>* Treatment of stenoses with primary percutaneous transluminal angioplasty (PTA) and placement of the Covera Vascular Covered Stent.<br>|
| Active Comparator: PTA only using uncoated PTA Balloon<br>Percutaneous Transluminal Angioplasty (PTA) will be performed using a commercially available uncoated PTA balloon. Balloons with an external wire support, cutting/scoring component or other similar modifications are not permitted. Multiple balloons, inflations and/or prolonged inflation may be used. | Procedure: Percutaneous Transluminal Angioplasty (PTA) with Uncoated PTA Balloon<br>* Treatment of stenoses with PTA only<br>* Other names: Standard Balloon Angioplasty (POBA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness Endpoint: Number of Participants With Target Lesion Primary Patency (TLPP) | TLPP is defined as the interval following the index intervention until the next clinically driven reintervention at, or adjacent to,the original treatment site or until the extremity is abandoned for permanent access. Primary patency ends when any of the following occurs: a) clinically driven reintervention in the treatment area; b) thrombotic occlusion within the treatment area; c) surgical intervention that excludes the original treatment area from the AV circuit, and/or d) abandonment of the AV fistula due to inability to treat the original treatment area. COVERA Vascular Covered Stent (following PTA) is evaluated against subjects treated PTA alone. | 6 months post index procedure | 
| Number of Participants With Freedom From AV Access Circuit Localized or Systemic Serious Adverse Events | Safety is defined as freedom from any adverse event(s) (AEs), localized or systemic, that reasonably suggests the involvement of the AV access circuit (not including stenosis or thrombosis) that require or result in any of the following alone or in combination: additional interventions (including surgery); in-patient hospitalization or prolongation of an existing hospitalization; or death. | 30 days post index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Target Lesion Primary Patency (TLPP) at 12 Months Post Index Procedure | TLPP is defined as the interval following the index intervention until the next clinically driven reintervention at the original treatment site or until the extremity is abandoned for permanent access. Primary patency ends when any of the following occurs: a) clinically driven reintervention in the treatment area; b) thrombotic occlusion within the treatment area; c) surgical intervention that excludes the original treatment area from the AV circuit, and/or d) abandonment of the AV fistula due to inability to treat the original treatment area. | 12 months post-index procedure | 
| Number of Participants With Access Circuit Primary Patency (ACPP). | ACPP is defined as the interval following the index intervention until the next access thrombosis or repeated intervention. ACPP ends with a reintervention anywhere within the access circuit. Vessel rupture caused by PTA is not an ACPP failure unless achieving hemostasis also causes thrombosis. Testing of this secondary endpoint is performed in a hierarchical fashion. Thus, In order to perform hypothesis test of ACPP at 6-month, TLPP at 12-months must be successful. | 6 months post index procedure | 
| Number of Participants With Target Lesion Primary Patency (TLPP) | Defined as the interval following the index intervention until the next clinically driven reintervention at the original treatment site or until the extremity is abandoned for permanent access. mITT subjects results are presented. N= number of subjects in the mITT Population with evaluable data. Evaluation through 1, 3, 18 and 24 months post index procedure. | 1, 3, 18 and 24 months post index procedure | 
| Number of Participants With Access Circuit Primary Patency (ACPP) | ACPP is defined as the interval following the index intervention until the next access thrombosis or repeated intervention. N = number of subjects in the mITT Population with evaluable data. | 1, 3, 12, 18, and 24 months post index procedure | 
| Number of Participants Free From Device and Procedure Related AEs Involving the AV Access Circuit | Number of Participants Free from Device and Procedure Related AEs Involving the AV Access Circuit (ITT population). Number of participants (n) in each follow-up periods varies from overall enrollment (N) as some subjects discontinued participation before the 30 days, 90 days and 6 months follow-up or did not meet endpoint inclusion criteria. The relationships with device/procedure of the events are based on CEC adjudications. | Evaluation through 1, 3, 6, 12, 18, and 24 months post-index procedure | 
| Total Number of Arteriovenous (AV) Access Circuit Reinterventions | Defined as the number of reinterventions to the AV access circuit until access abandonment or through study completion. Whereas the outcome measure time frames for the overall study are 1, 3, 6, 12,18 and 24 months, the interim report only provides the 1, 3, and 6 months results. The 12,18 and 24 months results will be provided in the final reporting for the study. MITT results are presented for this analysis. | 1, 3, 6, 12, 18 and 24 months post index procedure | 
| Total Number of Target Lesion Reinterventions | Total Number of Target Lesion Reinterventions defined as the number of reinterventions to maintain target lesion patency (mITT subjects). Whereas the outcome measure time frames for the overall study are 1, 3, 6, 12,18 and 24 months. | 1, 3, 6, 12, 18 and 24 months post index procedure | 
| Index of Patency Function (IPF) | IPF is defined as the time from the index study procedure to study completion or access abandonment divided by the number of visits for a reintervention performed on the AV access circuit in order to maintain vascular access for hemodialysis. A visit is defined as one (1) procedural event, regardless of the number or type of interventions performed during the visit. The index procedure is counted as the first visit to ensure all subjects have a denominator of at least one. Whereas the measure time frames for the overall study are 1, 3, 6, 12,18 and 24 months. The IPF is representative of the number of days between interventions to maintain access circuit patency. Higher values represent a better outcome, that is, more time elapsed between the Index study procedure and reinterventions. mITT results are analyzed. | 1, 3, 6, 12, 18 and 24 months post index procedure | 
| Index of Patency Function - Target Lesion (IPF-T) | IPF-T (Index of Patency Function - Target Lesion) is defined as the time from the index study procedure to study completion or complete access abandonment divided by the number of visits for a reintervention performed at the target lesion in order to maintain vascular access for hemodialysis. Whereas the measure time frames for the overall study are 1, 3, 6, 12, 18 and 24 months. The IPF for target lesion patency is representative of the approximate (mean) number of days between interventions to maintain target lesion patency. Higher values represent a better outcome, that is, more time elapsed between the Index study procedure and reinterventions. | 1, 3, 6, 12, 18 and 24 months post index procedure | 
| Number of Participants With Post-intervention Secondary Patency | Secondary Patency is defined as the interval after the index intervention until the access is abandoned. Multiple repetitive treatments can be included in post-intervention secondary patency. Whereas the measure time frames for the overall study are 1, 3, 6, 12,18 and 24 months, the interim report only provides the 1, 3, and 6 months results. The 12,18 and 24 months results will be provided in the final reporting for the study. mITT subjects results are presented. | 1, 3, 6, 12, 18 and 24 months post index procedure | 
| Number of Participants With Technical Success | Technical Success is defined as successful deployment, based on the operator's opinion, of the implant to the intended location assessed at the time of the index procedure. Therefore, for this measure, only COVERA data are relevant. mITT results are presented. Number of participants (n) included in this analysis is different from overall enrollment (N) as some subjects discontinued participation before the 30 days, 90 days and 6 months follow-up or did not meet endpoint inclusion criteria. Technical success was assessed on the day the index procedure was performed, which may be a different day for each participant. | On Day of Index Procedure | 
| Number of Participants With Procedure Success | Procedure Success is defined as anatomic success and resolution of the pre-procedural clinical indicator(s) (clinical success) of a hemodynamically significant stenosis. Procedure success was assessed on the day the index procedure was performed, which may be a different day for each participant. | On Day of Index Procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESRD, Stenosis, Restenosis, Hemodialysis, AV Fistula, Arteriovenous (AV)