Vorapaxar Study for Maturation of AV Fistulae for Hemodialysis Access

NCT ID: NCT02475837

Last Updated: 2019-01-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-26

Study Completion Date

2017-10-23

Brief Summary

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The Objectives of this study are:

1. To determine if vorapaxar safely improves arteriovenous (AV) fistula functional maturation when administered during the maturation process compared with placebo.
2. To determine if vorapaxar safely improves AV fistula patency, allowing for secondary procedures to aid in fistula maturation compared with placebo.
3. To determine if vorapaxar safely facilitates successful cannulation of AV fistulas for hemodialysis compared with placebo.

This is a randomized placebo-controlled double-blind pilot trial. Study procedures will be conducted at Stanford University Medical Center, and standard-of-care (SOC) procedures will be conducted at Stanford and it's affiliated hospitals (Veteran's Affairs Palo Alto Health Care System and the Stanford Vascular Surgery Clinic at Valley Medical Center). The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm).

Detailed Description

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Objectives:

1. To determine if vorapaxar safely improves arteriovenous (AV) fistula functional maturation when administered during the maturation process compared with placebo.
2. To determine if vorapaxar safely improves AV fistula patency, allowing for secondary procedures to aid in fistula maturation compared with placebo.
3. To determine if vorapaxar safely facilitates successful cannulation of AV fistulas for hemodialysis compared with placebo.

This is a randomized placebo-controlled double-blind pilot trial. Study procedures will be conducted at Stanford University Medical Center, and standard-of-care (SOC) procedures will be conducted at Stanford and it's affiliated hospitals (Veteran's Affairs Palo Alto Health Care System and the Stanford Vascular Surgery Clinic at Valley Medical Center). The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm).

Participation in this study will not affect standard care of patients with AV fistulae receiving hemodialysis. The only additional treatment is administration of the study drug or placebo and additional monitoring, including one additional ultrasound, for 6 months.

Conditions

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AV Fistula

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vorapaxar intervention

This arm will receive the study drug: Vorapaxar sulfate.

The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm).

Group Type ACTIVE_COMPARATOR

Vorapaxar sulfate

Intervention Type DRUG

The study drug (12-week supply of study drug) will be dispensed to enrolled patients on the first day following surgery.

Placebo intervention

This arm will receive the matching placebo.

The investigators expect to enroll 128 patients. Patients will be assigned to treatment groups with a 1:1 randomization in blocks of 4 at the conclusion of the AV fistula creation. Patients will be stratified based on fistula location (lower arm versus upper arm).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

The placebo will match the study drug, vorapaxar sulfate, in appearance. A 12-week supply will be dispensed to enrolled patients on the first day following surgery.

Interventions

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Vorapaxar sulfate

The study drug (12-week supply of study drug) will be dispensed to enrolled patients on the first day following surgery.

Intervention Type DRUG

Placebo

The placebo will match the study drug, vorapaxar sulfate, in appearance. A 12-week supply will be dispensed to enrolled patients on the first day following surgery.

Intervention Type DRUG

Other Intervention Names

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Zontivity

Eligibility Criteria

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Inclusion Criteria

1. Age \>18
2. Receiving or planning to receive maintenance hemodialysis
3. Ability to sign informed consent
4. 3 mm venous diameter within recipient vein

Exclusion Criteria

1. History of stroke, transient ischemic attack or intracranial hemorrhage
2. History of or high level of suspicion for, severe arterial insufficiency of the hand
3. Indication or ongoing therapy with other antiplatelet agents, other than aspirin 81 mg daily
4. Indication or ongoing therapy with anticoagulants, including warfarin, low molecular weight heparin, factor Xa inhibitors or direct thrombin and other inhibitors.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Ken Mahaffey

OTHER

Sponsor Role lead

Responsible Party

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Ken Mahaffey

Co Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Matthew W Mell, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Kenneth W Mahaffey, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford Univeristy

Stanford, California, United States

Site Status

Countries

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United States

References

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Brescia MJ, Cimino JE, Appel K, Hurwich BJ. Chronic hemodialysis using venipuncture and a surgically created arteriovenous fistula. N Engl J Med. 1966 Nov 17;275(20):1089-92. doi: 10.1056/NEJM196611172752002. No abstract available.

Reference Type BACKGROUND
PMID: 5923023 (View on PubMed)

Andrassy K, Malluche H, Bornefeld H, Comberg M, Ritz E, Jesdinsky H, Mohring K. Prevention of p.o. clotting of av. cimino fistulae with acetylsalicyl acid. Results of a prospective double blind study. Klin Wochenschr. 1974 Apr 1;52(7):348-9. doi: 10.1007/BF01468835. No abstract available.

Reference Type BACKGROUND
PMID: 4600820 (View on PubMed)

Crowther MA, Clase CM, Margetts PJ, Julian J, Lambert K, Sneath D, Nagai R, Wilson S, Ingram AJ. Low-intensity warfarin is ineffective for the prevention of PTFE graft failure in patients on hemodialysis: a randomized controlled trial. J Am Soc Nephrol. 2002 Sep;13(9):2331-7. doi: 10.1097/01.asn.0000027356.16598.99.

Reference Type BACKGROUND
PMID: 12191977 (View on PubMed)

Fiskerstrand CE, Thompson IW, Burnet ME, Williams P, Anderton JL. Double-blind randomized trial of the effect of ticlopidine in arteriovenous fistulas for hemodialysis. Artif Organs. 1985 Feb;9(1):61-3. doi: 10.1111/j.1525-1594.1985.tb04349.x.

Reference Type BACKGROUND
PMID: 3888153 (View on PubMed)

Osborn G, Escofet X, Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD002786. doi: 10.1002/14651858.CD002786.pub2.

Reference Type BACKGROUND
PMID: 18843633 (View on PubMed)

Kaufman JS. Antithrombotic agents and the prevention of access thrombosis. Semin Dial. 2000 Jan-Feb;13(1):40-6. doi: 10.1046/j.1525-139x.2000.00012.x. No abstract available.

Reference Type BACKGROUND
PMID: 10740671 (View on PubMed)

Dember LM, Kaufman JS, Beck GJ, Dixon BS, Gassman JJ, Greene T, Himmelfarb J, Hunsicker LG, Kusek JW, Lawson JH, Middleton JP, Radeva M, Schwab SJ, Whiting JF, Feldman HI; DAC Study Group. Design of the Dialysis Access Consortium (DAC) Clopidogrel Prevention of Early AV Fistula Thrombosis Trial. Clin Trials. 2005;2(5):413-22. doi: 10.1191/1740774505cn118oa.

Reference Type BACKGROUND
PMID: 16317810 (View on PubMed)

Hirano K. The roles of proteinase-activated receptors in the vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):27-36. doi: 10.1161/01.ATV.0000251995.73307.2d. Epub 2006 Nov 9.

Reference Type BACKGROUND
PMID: 17095716 (View on PubMed)

Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJ, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA; TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012 Apr 12;366(15):1404-13. doi: 10.1056/NEJMoa1200933. Epub 2012 Mar 24.

Reference Type BACKGROUND
PMID: 22443427 (View on PubMed)

Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, White HD, Aylward PE, Wallentin L, Chen E, Lokhnygina Y, Pei J, Leonardi S, Rorick TL, Kilian AM, Jennings LH, Ambrosio G, Bode C, Cequier A, Cornel JH, Diaz R, Erkan A, Huber K, Hudson MP, Jiang L, Jukema JW, Lewis BS, Lincoff AM, Montalescot G, Nicolau JC, Ogawa H, Pfisterer M, Prieto JC, Ruzyllo W, Sinnaeve PR, Storey RF, Valgimigli M, Whellan DJ, Widimsky P, Strony J, Harrington RA, Mahaffey KW; TRACER Investigators. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012 Jan 5;366(1):20-33. doi: 10.1056/NEJMoa1109719. Epub 2011 Nov 13.

Reference Type BACKGROUND
PMID: 22077816 (View on PubMed)

Kosoglou T, Kraft WK, Kumar B, Statkevich P, Xuan F, Ma L, Jennings LK, Schiller JE, Langdon RB, Cutler DL. Pharmacokinetics and pharmacodynamics of the novel PAR-1 antagonist vorapaxar in patients with end-stage renal disease. Eur J Clin Pharmacol. 2012 Jul;68(7):1049-56. doi: 10.1007/s00228-012-1217-6. Epub 2012 Feb 8.

Reference Type BACKGROUND
PMID: 22315147 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

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http://www.usrds.org/atlas.aspx

1\. United States Renal Data System 2013 Annual Report, Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases.

Other Identifiers

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33763

Identifier Type: -

Identifier Source: org_study_id

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