Vorapaxar Study for Maturation of AV Fistulae for Hemodialysis Access

AV Fistula Clinical Trial

Official title:

A Double-blind, Randomized, Placebo Controlled Pilot Trial to Evaluate the Safety and Efficacy of Vorapaxar in Maturation of Arteriovenous Fistulae for Hemodialysis Access

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02475837
• Other study ID #: 33763
• Status: Completed
• Phase: Phase 2
• Start date: August 26, 2015
• Est. completion date: October 23, 2017

Study information

• Verified date: January 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: October 23, 2017
• Est. primary completion date: October 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arteriovenous Fistula
• AV Fistula
• Fistula

Intervention

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

Locations

Country	Name	City	State
United States	Stanford Univeristy	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Ken Mahaffey	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (11)

Andrassy K, Malluche H, Bornefeld H, Comberg M, Ritz E, Jesdinsky H, Möhring 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Hirano K. The roles of proteinase-activated receptors in the vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):27-36. Epub 2006 Nov 9. Review. — View Citation

Kaufman JS. Antithrombotic agents and the prevention of access thrombosis. Semin Dial. 2000 Jan-Feb;13(1):40-6. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2015;7:CD002786. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to AV Fistula Functional Maturation	Time to AV fistula functional maturation (defined as successful cannulation of the AV fistula for six hemodialysis sessions within three weeks).	up to 238 days
Secondary	Count of Participants With AV Fistula Use	Participants able to use their AV fistula for dialysis within 180 days of surgery were considered to have met the outcome.	up to 238 days
Secondary	Count Participants With AV Fistula Patency	Criteria for outcome: AV fistula patency at 150-180 days, with at least 50% increase in vein diameter by ultrasound compared with preoperative vein diameter measurement.	150-238 days
Secondary	Count of All Participants With Bleeding Events	Bleeding events according to GUSTO (criteria for bleeding: Severe, Moderate or Mild) and BARC (bleeding criteria Type 0-5, with 0 being no bleeding and 5 referring to probable or definite fatal bleeding) Criteria	up to 238 days

External Links

•   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.