Design of the Dialysis Access Consortium (DAC) Clopidogrel Prevention of Early AV Fistula Thrombosis Trial.
BACKGROUND
The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes. The autogenous arteriovenous fistula created by direct connection of native artery to vein is the recommended vascular access for hemodialysis. However, it fails frequently due to clotting after surgery.


OBJECTIVE
The DAC Early AV Fistula Thrombosis Trial tests the hypothesis that clopidogrel can prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access. This is one of two initial and concurrent trials being performed by the DAC. The companion trial investigates pharmacologic approaches to prevent venous stenosis leading to AV graft failure.


METHODS
This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,284 patients over four years. Patients undergoing creation of a new native arteriovenous (AV) fistula are randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery. The primary outcome is fistula patency at six weeks. The major secondary outcome is fistula suitability for dialysis.


RESULTS
This paper examines key aspects of this study that have broad relevance to trial design including: 1) the selection of an intermediate event as the primary outcome, 2) timing of the intervention to balance efficacy and safety concerns, 3) ethical considerations arising from required modifications of concomitant drug therapy, and 4) choosing an efficacy or effectiveness evaluation of the intervention.


CONCLUSIONS
This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent early AV fistula failure and promote more usable fistulas for hemodialysis. The methodologic challenges identified and addressed during the development of this trial should help to inform the design of future vascular access trials, and are relevant to clinical trials addressing a wide range of questions.
Dember
Laura M
LM
Renal Section, Boston University School of Medicine, MA 02118 USA. ldember@bu.edu
Kaufman
James S
JS
Beck
Gerald J
GJ
Dixon
Bradley S
BS
Gassman
Jennifer J
JJ
Greene
Tom
T
Himmelfarb
Jonathan
J
Hunsicker
Lawrence G
LG
Kusek
John W
JW
Lawson
Jeffrey H
JH
Middleton
John P
JP
Radeva
Milena
M
Schwab
Steve J
SJ
Whiting
James F
JF
Feldman
Harold I
HI
D001166:Arteriovenous Shunt, Surgical; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D015337:Multicenter Studies as Topic; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D012107:Research Design; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin