Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.
BACKGROUND
Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF.


METHODS
The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding.


CONCLUSIONS
This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has shown that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Our study presents significant differences in the anti-platelet agents used, the study design, and surgical and patient demographics that should contribute further evidence regarding the efficacy of anti-platelet agents.


BACKGROUND
Australia & New Zealand Clinical Trials Register (ACTRN12607000569404).
Irish
Ashley
A
Renal Unit, Royal Perth Hospital, Perth, WA, Australia. ashley.irish@health.wa.gov.au
Dogra
Gursharan
G
Mori
Trevor
T
Beller
Elaine
E
Heritier
Stephane
S
Hawley
Carmel
C
Kerr
Peter
P
Robertson
Amanda
A
Rosman
Johan
J
Paul-Brent
Peta-Anne
PA
Starfield
Melissa
M
Polkinghorne
Kevan
K
Cass
Alan
A
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D015337:Multicenter Studies as Topic / Q000379:methods; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D014654:Vascular Patency / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor; D001241:Aspirin