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

• Lutonix DCB (Combination product)
• Standard Balloon Angioplasty Catheter (Device)
• Percutaneous Transluminal Angiography (Procedure), also known as PTA: 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.

Primary outcomes

• Percentage of Participants With Target Lesion Primary Patency (TLPP) at 6 Months Post Index Procedure [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.
• Number of Participants With Freedom From Any Serious Adverse Event(s) Involving the AV Access Circuit at 30 Days Post Index Procedure. [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).

Secondary outcomes

• Percentage of Participants With Target Lesion Primary Patency at 3, 9, 12, 18, and 24 Months [3, 9, 12, 18, and 24 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.
• Percentage of Participants With Device, Procedural and Clinical Success [Device and Procedural Success: At time of Index Procedure; Clinical Success: at 1st session of dialysis following index procedure]: * 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.
• Number of Participants With Abandonment of Permanent Access in the Index Extremity at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure [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.
• 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) [1, 3, 6, 9, 12, 18 and 24 Months Post Index Procedure]: Events adjudicated as 'definitely related' and 'possibly related' by the CEC were combined in all analyses and are displayed as 'related' in this report.
• Number of Participants With Target Lesion Primary Patency (TLPP) by Fiber Pre-Dilation Balloon at 6 Months Post Index Procedure [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.
• 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]

Sex: All, ages: 21 Years to any

Inclusion Criteria:

1. Age ≥21 years;
2. 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);
3. Arteriovenous fistula located in the arm;
4. Native AV fistula was created ≥30 days prior to the index procedure and has undergone one or more hemodialysis sessions;
5. 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.;
6. Successful pre-dilation of the target lesion with a percutaneous transluminal angioplasty (PTA) balloon;
7. Intended target lesion.

Exclusion Criteria:

1. Women who are pregnant, lactating, or planning on becoming pregnant during the study;
2. Hemodialysis access is located in the leg;
3. Subject has more than two lesions in the access circuit;
4. Subject has a secondary non-target lesion that cannot be successfully treated;
5. Target lesion is located central to the axillosubclavian junction;
6. The subject has a secondary lesion located in the central venous system (central to the axillosubclavian junction);
7. A thrombosed access;
8. Surgical revision of the access site planned;
9. Recent prior surgical interventions of the access site;
10. Other planned treatment during the index procedure;
11. Known contraindication (including allergic reaction) or sensitivity to iodinated contrast media, that cannot be adequately managed with pre-and post-procedure medication;
12. Known contraindication (including allergic reaction) or sensitivity to paclitaxel.
13. Subjects who are taking immunosuppressive therapy or are routinely taking

    ≥10mg of prednisone per day;
14. 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;
15. Subject has a life expectancy <12 months;
16. Anticipated for a kidney transplant;
17. Anticipated conversion to peritoneal dialysis;
18. Subject has a stent located in the target or secondary non target lesion;
19. Subject has an infected AV access or systemic infection;
20. Currently participating in an investigational drug, biologic, or device study, or previous enrollment in this study.

Participant flow

Outcome results

• Percentage of Participants With Target Lesion Primary Patency (TLPP) at 6 Months Post Index Procedure (Primary), Number, Percentage of Participants: Lutonix DCB 71.4 (62.7 to 78.4); Standard Balloon Angioplasty Catheter 63 (54.4 to 70.4) (p 0.0562)
• Number of Participants With Freedom From Any Serious Adverse Event(s) Involving the AV Access Circuit at 30 Days Post Index Procedure. (Primary), Count of participants, Participants: Lutonix DCB 130; Standard Balloon Angioplasty Catheter 138 (p 0.002)
• Percentage of Participants With Target Lesion Primary Patency at 3, 9, 12, 18, and 24 Months (Secondary), Number, Percentage of Participants: Lutonix DCB 92.6 (86.6 to 95.9); Standard Balloon Angioplasty Catheter 86.7 (79.9 to 91.3)
• Percentage of Participants With Device, Procedural and Clinical Success (Secondary), Number, Percentage of participants: Lutonix DCB 100; Standard Balloon Angioplasty Catheter 100
• Number of Participants With Abandonment of Permanent Access in the Index Extremity at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure (Secondary), Count of participants, Participants: Lutonix DCB 3; Standard Balloon Angioplasty Catheter 0
• Number of Interventions Required to Maintain Access Circuit Primary Patency (ACPP) at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure (Secondary), Number, Interventions: Lutonix DCB 21; Standard Balloon Angioplasty Catheter 20
• Number of Participants With Device Related Adverse Events at 1, 3, 6, 9, 12, 18, and 24 Months (CEC Adjudicated) (Secondary), Count of participants, Participants: Lutonix DCB 5; Standard Balloon Angioplasty Catheter 1
• Number of Participants With Target Lesion Primary Patency (TLPP) by Fiber Pre-Dilation Balloon at 6 Months Post Index Procedure (Secondary), Count of participants, Participants: Lutonix DCB 57; Standard Balloon Angioplasty Catheter 48 (p 0.7160)
• Number of Interventions Required to Maintain Target Lesion Primary Patency (TLPP) at 3, 6, 9, 12, 18, and 24 Months Post Index Procedure (Secondary), Number, Interventions: Lutonix DCB 19; Standard Balloon Angioplasty Catheter 11
• Number of Procedure Related Serious Adverse Events (CEC Adjudicated) at 1, 3, 6, 9, 12, 18, and 24 Months Post Index Procedure (Secondary), Number, Events: Lutonix DCB 8; Standard Balloon Angioplasty Catheter 2

Adverse events

Time frame: At 24 months Post Index Procedure

Serious adverse events by term

Other adverse events by term

• Results publication: Trerotola SO, Lawson J, Roy-Chaudhury P, Saad TF; Lutonix AV Clinical Trial Investigators. Drug Coated Balloon Angioplasty in Failing AV Fistulas: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2018 Aug 7;13(8):1215-1224. doi: 10.2215/CJN.14231217. Epub 2018 Jul 24. PMID 30042225

• Study Protocol and Statistical Analysis Plan (PDF, 2015-11-30)

• Scott Trerotola, MD, Principal investigator, University of Pennsylvania