Clopidogrel Prevention of Early Arteriovenous (AV) Fistula Thrombosis (FISTULA)

Effect of Clopidogrel on Early Failure of Arteriovenous Fistulas for Hemodialysis

The objective of the study is to determine whether clopidogrel reduces the early failure rate of native AV fistulae. This study was originally registered as NCT00067119 which included two protocols, this one and the GRAFT study)

Study Overview

• Status: Completed
• Conditions: Kidney Failure; Hemodialysis Fistula Thrombosis
• Intervention / Treatment: Drug: Placebo; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Actual): 877
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Fistula Study Protocol

Inclusion Criteria:

• Age 18-21 depending on state regulations
• Life expectancy of at least six months
• Chronic renal failure with anticipated start of hemodialysis within six months of enrollment, or current dialysis dependence
• Planned creation of native upper extremity AV fistula
• The patient is not on aspirin, or the patient is on aspirin but has not had a myocardial infarction or a cerebrovascular accident within the past 12 months.
• The patient is expected to stay at a participating dialysis facility for at least 6 months.
• The patient's physician(s) will allow the patient to participate.
• Ability to give informed consent.

Exclusion Criteria:

• Women must not be pregnant, breastfeeding, or plan to be pregnant during the course of the study.
• The presence of ongoing bleeding.
• The presence of a known bleeding disorder (e.g., hemophilia or von Willebrand's disease).
• Recent bleeding episode requiring transfusion within 12 weeks of entry.
• The presence of acute ulcer disease. Acute ulcer disease is defined as a new diagnosis of peptic disease including esophagitis, gastritis, or ulcer or the initiation of treatment with proton pump inhibitors, H2 blockers or therapy for Helicobacter pylori within three months prior to obtaining consent.
• A condition which prohibits discontinuation of anticoagulant drugs, aspirin, or nonsteroidal anti-inflammatory drugs during the six week study drug administration period. Use of heparin during dialysis is allowed.
• Required use of oral or intravenous glucocorticoids at a dose greater than the equivalent of prednisone 15 mg per day during the six week study drug administration period.
• Current unstable angina.
• Required use of clopidogrel.
• Known hypersensitivity to clopidogrel.
• Medical considerations making anti-platelet therapy dangerous.
• Current uncontrolled hypertension with systolic blood pressure in excess of 200 mm Hg or diastolic blood pressure in excess of 115 mm Hg at the time of enrollment.
• Baseline platelet count less than 75,000/mm3.
• Known advanced liver disease with decompensated cirrhosis, jaundice, ascites or bleeding varices.
• Current problem with substance abuse.
• Concurrent participation in another medical intervention trial.
• Anticipated non-compliance with medical care based on physician judgment.
• Patient refusal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Clopidogrel	Drug: Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fistula thrombosis (patency failure)	The fistula was classified as patent if a bruit was audible with a stethoscope throughout systole and diastole at least 8 cm proximal to the arteriovenous anastomosis. Fistula patency was assessed by trained study personnel.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure to attain suitability for dialysis (ability to use the fistula for dialysis with 2 needles and maintain a dialysis machine blood flow rate adequate for optimal dialysis (>=300 mL/min))	Fistula suitability was defined as the ability to use the fistula for dialysis with 2 needles and maintain a dialysis machine blood flow rate adequate for optimal dialysis (>=300 mL/min) during 8 of 12 dialysis sessions occurring during a 30-day suitability ascertainment period. For participants receiving maintenance hemodialysis at the time of enrollment and for participants who started maintenance hemodialysis within 120 days after fistula creation, the suitability ascertainment period began between 120 and 150 days after fistula creation surgery.	30 days

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Boston University; Washington University School of Medicine; University of Alabama at Birmingham; University of Iowa; The Cleveland Clinic; Emory University; Duke University; Vanderbilt University; University of Texas Southwestern Medical Center; CAMC Health System; Baystate Medical Center; St. Louis University; MaineHealth; Tyler Nephrology Associates; Vascular Surgery Associates LLC
• Investigators: Study Director: John W Kusek, Ph.D., NIDDK - Telephone: 301-594-7717; Email: kusekj@ep.niddk.nih.gov; Study Director: Catherine Meyers, M.D., NIDDK - Telephone: 301-451-4901; Email: meyersc@extra.niddk.nih.gov

Publications and helpful links

General Publications

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
• 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.
• Dember LM, Beck GJ, Allon M, Delmez JA, Dixon BS, Greenberg A, Himmelfarb J, Vazquez MA, Gassman JJ, Greene T, Radeva MK, Braden GL, Ikizler TA, Rocco MV, Davidson IJ, Kaufman JS, Meyers CM, Kusek JW, Feldman HI; Dialysis Access Consortium Study Group. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA. 2008 May 14;299(18):2164-71. doi: 10.1001/jama.299.18.2164.

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2003
• Primary Completion (Actual): June 18, 2007
• Study Completion (Actual): June 18, 2007

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 21, 2017

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Hemodialysis; Vascular Access; Access Blood Flow Monitoring; Clinical Trial Vascular Access; Fistula Failure
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Ticlopidine; Thienopyridines; Clopidogrel
• Other Study ID Numbers: DAC Fistula; U01DK058982 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository
• IPD Sharing Time Frame: September 2011
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No