Study Comparing Lutonix AV Drug Coated Balloon vs Standard Balloon for Treatment of Dysfunctional AV Fistulae

Study Overview
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Brief Summary
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This prospective, global, multicenter, randomized, controlled study is designed to evaluate the safety and effectiveness of the Lutonix 035 AV Drug Coated Balloon PTA Catheter compared to a standard PTA Catheter in treating subjects presenting with clinical and hemodynamic abnormalities in native arteriovenous (AV) fistulae located in the upper extremity.

Official Title
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A Prospective, Global, Multicenter, Randomized, Controlled Study Comparing Lutonix® 035 AV Drug Coated Balloon PTA Catheter vs. Standard Balloon PTA Catheter for the Treatment of Dysfunctional AV Fistulae

Conditions
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Arteriovenous Fistula

Intervention / Treatment
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* Combination Product: Lutonix DCB
* Device: Standard Balloon Angioplasty Catheter
* Procedure: Percutaneous Transluminal Angiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥21 years; The subject is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions, and has duly signed the informed consent form (ICF); Arteriovenous fistula located in the arm; Native AV fistula was created ≥30 days prior to the index procedure and has undergone one or more hemodialysis sessions; Venous stenosis of an AV fistula with the target lesion located from the anastomosis to the axillosubclavian junction and an abnormality attributable to the stenosis as defined by K/DOQI guidelines.; Successful pre-dilation of the target lesion with a percutaneous transluminal angioplasty (PTA) balloon; Intended target lesion. Exclusion Criteria: Women who are pregnant, lactating, or planning on becoming pregnant during the study; Hemodialysis access is located in the leg; Subject has more than two lesions in the access circuit; Subject has a secondary non-target lesion that cannot be successfully treated; Target lesion is located central to the axillosubclavian junction; The subject has a secondary lesion located in the central venous system (central to the axillosubclavian junction); A thrombosed access; Surgical revision of the access site planned; Recent prior surgical interventions of the access site; Other planned treatment during the index procedure; Known contraindication (including allergic reaction) or sensitivity to iodinated contrast media, that cannot be adequately managed with pre-and post-procedure medication; Known contraindication (including allergic reaction) or sensitivity to paclitaxel. Subjects who are taking immunosuppressive therapy or are routinely taking ≥10mg of prednisone per day; Subject has another medical condition, which, in the opinion of the Investigator, may cause him/her to be noncompliant with the protocol or confound the data interpretation; Subject has a life expectancy <12 months; Anticipated for a kidney transplant; Anticipated conversion to peritoneal dialysis; Subject has a stent located in the target or secondary non target lesion; Subject has an infected AV access or systemic infection; Currently participating in an investigational drug, biologic, or device study, or previous enrollment in this study.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lutonix DCB<br>Percutaneous transluminal angiography (PTA) will be performed using the Lutonix AV drug coated balloon. | Combination Product: Lutonix DCB<br> <br> Procedure: Percutaneous Transluminal Angiography<br>* Percutaneous transluminal angioplasty (PTA) is a procedure that can open up a blocked blood vessel using a small, flexible plastic tube, or catheter, with a balloon at the end of it. When the tube is in place, it inflates to open the blood vessel, or artery, so that normal blood flow is restored.<br>* Other names: PTA;|
| Active Comparator: Standard Balloon Angioplasty Catheter<br>Percutaneous transluminal angiography (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. | Device: Standard Balloon Angioplasty Catheter<br> <br> Procedure: Percutaneous Transluminal Angiography<br>* Percutaneous transluminal angioplasty (PTA) is a procedure that can open up a blocked blood vessel using a small, flexible plastic tube, or catheter, with a balloon at the end of it. When the tube is in place, it inflates to open the blood vessel, or artery, so that normal blood flow is restored.<br>* Other names: PTA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Target Lesion Primary Patency (TLPP) at 6 Months Post Index Procedure | Primary Patency is defined as the interval following index procedure intervention until clinically driven reintervention of the target lesion or access thrombosis. Target Lesion Primary Patency (TLPP) ends with a clinically driven re-intervention of the target lesion or access thrombosis. | 6 months post index procedure | 
| Number of Participants With Freedom From Any Serious Adverse Event(s) Involving the AV Access Circuit at 30 Days Post Index Procedure. | The primary safety endpoint is freedom from localized or systemic serious adverse events through 30 days that reasonably suggests the involvement of the AV access circuit (CEC adjudicated). | 30 Days Post Index Procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Target Lesion Primary Patency at 3, 9, 12, 18, and 24 Months | Primary Patency is defined as the interval following index procedure intervention until clinically driven reintervention of the target lesion or access thrombosis. Target Lesion Primary Patency (TLPP) ends with a clinically driven re-intervention of the target lesion or access thrombosis. | 3, 9, 12, 18, and 24 Months Post Index Procedure | 
| Percentage of Participants With Device, Procedural and Clinical Success | Device Success: Successful delivery to the target lesion, deployment, and retrieval at index procedure. Procedural Success: At least one indicator of hemodynamic success (e.g., physical examination with restoration of a thrill, direct measurement of flow) in the absence of peri-procedural (index procedure and through hospital stay) Serious Adverse Device Effects (SADEs). Clinical Success: The resumption of dialysis for at least one session after the index procedure. | Device and Procedural Success: At time of Index Procedure; Clinical Success: at 1st session of dialysis following index procedure | 
| Number of Participants With Abandonment of Permanent Access in the Index Extremity at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure | Index access site abandonment refers to an abandonment due to either receiving a kidney transplant, converting to Peritoneal Dialysis, or a new access site being created. | 3, 6, 9, 12, 18 and 24 Months Post Index Procedure | 
| Number of Interventions Required to Maintain Access Circuit Primary Patency (ACPP) at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure |  | 3, 6, 9, 12, 18 and 24 Months Post Index Procedure | 
| Number of Participants With Device Related Adverse Events at 1, 3, 6, 9, 12, 18, and 24 Months (CEC Adjudicated) | Events adjudicated as 'definitely related' and 'possibly related' by the CEC were combined in all analyses and are displayed as 'related' in this report. | 1, 3, 6, 9, 12, 18 and 24 Months Post Index Procedure | 
| Number of Participants With Target Lesion Primary Patency (TLPP) by Fiber Pre-Dilation Balloon at 6 Months Post Index Procedure | Primary Patency is defined as the interval following index procedure intervention until clinically driven reintervention of the target lesion or access thrombosis. Target Lesion Primary Patency (TLPP) ends with a clinically driven re-intervention of the target lesion or access thrombosis. | 6 Months Post Index Procedure | 
| Number of Interventions Required to Maintain Target Lesion Primary Patency (TLPP) at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure |  | 3, 6, 9, 12, 18, and 24 Months Post Index Procedure | 
| Number of Procedure Related Serious Adverse Events (CEC Adjudicated) at 1, 3, 6, 9, 12, 18, and 24 Months Post Index Procedure |  | 1, 3, 6, 9, 12, 18, and 24 Months Post Index Procedure |