Vascular Access Clinical Trials Data Coordinating Center

Fistula Study: The objective of the study is to determine whether clopidogrel reduces the early failure rate of native AV fistulae.

Graft Study: The objective of the study is to determine whether Aggrenox (Boehringer-Ingelheim) prolongs primary unassisted patency in newly created arteriovenous grafts.

• Drug: Aggrenox
• Drug: Clopidogrel

• 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.
• Dixon BS, Beck GJ, Dember LM, Depner TA, Gassman JJ, Greene T, Himmelfarb J, Hunsicker LG, Kaufman JS, Lawson JH, Meyers CM, Middleton JP, Radeva M, Schwab SJ, Whiting JF, Feldman HI; DAC Study Group. Design of the Dialysis Access Consortium (DAC) Aggrenox Prevention Of Access Stenosis Trial. Clin Trials. 2005;2(5):400-12.
• Dixon BS, Beck GJ, Vazquez MA, Greenberg A, Delmez JA, Allon M, Dember LM, Himmelfarb J, Gassman JJ, Greene T, Radeva MK, Davidson IJ, Ikizler TA, Braden GL, Fenves AZ, Kaufman JS, Cotton JR Jr, Martin KJ, McNeil JW, Rahman A, Lawson JH, Whiting JF, Hu B, Meyers CM, Kusek JW, Feldman HI; DAC Study Group. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med. 2009 May 21;360(21):2191-201.
• 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.

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 dudring 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 equvalent 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.

Graft 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
• A new or planned AV graft placed in any location for the purpose of hemodialysis. (Any type of graft material and any configuration of the access is acceptable).
• 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.
• Known allergy or adverse reaction to Aggrenox or any of its study components (dipyridamole and aspirin).
• Required use of warfarin, dipyridamole, non-steroidal antiinflammatory drugs or other antiplatelet agents other than aspirin.
• Current uncontrolled hypertension with systolic blood pressure in excess of 200 mm Hg or diastolic blood pressure in excess of 115 mm Hg.
• 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.

• The Cleveland Clinic
• Boston University
• Duke University
• University of Iowa
• Maine Medical Center
• University of Texas Southwestern Medical Center
• University of Alabama at Birmingham
• Washington University School of Medicine
• Baystate Medical Center
• Vanderbilt University
• CAMC Health System
• Emory University
• St. Louis University
• Tyler Nephrology Associates
• Vascular Surgery Associates LLC