Design of the Dialysis Access Consortium (DAC) Aggrenox Prevention Of Access Stenosis Trial
Bradley S Dixon1, Gerald J Beck, Laura M Dember
1Nephrology Division, Veterans Affairs Medical Center and University of Iowa School of Medicine, Iowa City 52242-1081, USA. bradley-dixon@uiowa.edu
Insights
Aggrenox (dipyridamole and aspirin) was tested to prevent arteriovenous graft stenosis in hemodialysis patients. The trial addressed key design issues for future studies on this common vascular access problem.
Area of Science:
- Nephrology
- Vascular Surgery
- Clinical Trials
Background:
- Arteriovenous (AV) grafts are crucial for hemodialysis vascular access in the US.
- Venous stenosis frequently causes AV graft failure.
- The Dialysis Access Consortium (DAC) initiated a trial to evaluate Aggrenox for preventing AV graft stenosis.
Purpose of the Study:
- To test if Aggrenox (dipyridamole and aspirin) can prevent stenosis and prolong the survival of arteriovenous grafts.
- To establish a pharmacologic approach for preventing AV graft stenosis and failure.
Main Methods:
- A multicenter, randomized, double-blind, placebo-controlled trial involving 1056 subjects.
- Subjects received Aggrenox or placebo post-AV graft surgery.
- Primary outcome: primary unassisted patency; Secondary outcome: cumulative access patency.
- Monthly access flow monitoring to detect stenosis early.
Main Results:
- The paper details critical trial design considerations.
- Ethical issues, risk assessment (bleeding), subject inclusion criteria, intervention timing, and endpoint selection were addressed.
- This study provides a roadmap for future clinical trials in AV graft management.
Conclusions:
- This is the first large, multicenter trial assessing a drug to prevent AV graft stenosis.
- The findings address important design issues for future research in this patient population.
- The trial design provides a framework for future studies on preventing AV graft failure.
Background:
Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The Dialysis Access Consortium (DAC) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox (containing dipyridamole and aspirin) can prevent stenosis and prolong survival of arteriovenous grafts.
Methods:
This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up. Subjects undergoing placement of a new AV graft for hemodialysis are randomized to treatment with Aggrenox or placebo immediately following access surgery. The primary outcome is primary unassisted patency defined as the time from access placement until thrombosis or an access procedure carried out to maintain or restore patency. The major secondary outcome is cumulative access patency. Monthly access flow monitoring is incorporated in the study design to enhance detection of a hemodynamically significant access stenosis before it leads to thrombosis.
Results:
This paper describes the key issues in trial design, broadly including: 1) ethical issues surrounding the study of a clinical procedure that, although common, is no longer the clinical intervention of choice; 2) acceptable risk (bleeding) from the primary intervention; 3) inclusion of subjects already receiving a portion of the study intervention; 4) inclusion of subjects with incident rather than prevalent qualifying clinical conditions; 5) timing of the study intervention to balance safety and efficacy concerns; and 6) the selection of primary and secondary study endpoints.
Conclusions:
This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent AV graft stenosis and failure, an important and costly problem in this patient population. Numerous design issues were addressed in implementing the trial and these will form a roadmap for future trials in this area.
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