The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

Abstract

BACKGROUND:

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design.

METHODS/DESIGN:

The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure.

DISCUSSION:

This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study.

TRIAL REGISTRATION:

Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

• Authors: Andrea K Viecelli, Elaine Pascoe, Kevan R Polkinghorne, Carmel Hawley, Peta-Anne Paul-Brent, Sunil V Badve, Alan Cass, Stephane Heritier, Peter G Kerr, Trevor A Mori, Amanda Robertson, Hooi L Seong, Ashley B Irish, FAVOURED study team
• Journal: BMC nephrology (BMC Nephrol) Vol. 16 Pg. 89 (Jun 27 2015) ISSN: 1471-2369 [Electronic] England
• PMID: 26116581 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• Fatty Acids, Omega-3
• Fish Oils
• Platelet Aggregation Inhibitors
• Docosahexaenoic Acids
• Eicosapentaenoic Acid
• Omacor
• Aspirin

Topics

• Arteriovenous Shunt, Surgical (methods)
• Aspirin (therapeutic use)
• Central Venous Catheters (statistics & numerical data)
• Docosahexaenoic Acids (therapeutic use)
• Double-Blind Method
• Drug Combinations
• Drug Therapy, Combination
• Eicosapentaenoic Acid (therapeutic use)
• Fatty Acids, Omega-3 (therapeutic use)
• Fish Oils (therapeutic use)
• Humans
• Kidney Failure, Chronic (therapy)
• Platelet Aggregation Inhibitors (therapeutic use)
• Postoperative Complications (prevention & control)
• Renal Dialysis (methods)
• Renal Insufficiency, Chronic (therapy)
• Thrombosis (prevention & control)