title: 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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).
authors.affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia. andrea.viecelli@health.qld.gov.au.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Viecelli
authors.affiliation: Australasian Kidney Trials Network, School of Medicine, University of Queensland, Brisbane, QLD, Australia. e.pascoe@uq.edu.au.
authors.forename: Elaine
authors.initials: E
authors.lastname: Pascoe
authors.affiliation: Department of Nephrology, Monash Medical Centre, Melbourne, VIC, Australia. kevan.polkinghorne@monash.edu.|Departments of Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. kevan.polkinghorne@monash.edu.
authors.forename: Kevan R
authors.initials: KR
authors.lastname: Polkinghorne
authors.affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia. carmel.hawley@health.qld.gov.au.|Australasian Kidney Trials Network, School of Medicine, University of Queensland, Brisbane, QLD, Australia. carmel.hawley@health.qld.gov.au.
authors.forename: Carmel
authors.initials: C
authors.lastname: Hawley
authors.affiliation: Australasian Kidney Trials Network, School of Medicine, University of Queensland, Brisbane, QLD, Australia. p.kerr@uq.edu.au.
authors.forename: Peta-Anne
authors.initials: PA
authors.lastname: Paul-Brent
authors.affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia. sunil.badve@health.qld.gov.au.|Australasian Kidney Trials Network, School of Medicine, University of Queensland, Brisbane, QLD, Australia. sunil.badve@health.qld.gov.au.
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Badve
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, Australia. alan.cass@menzies.edu.au.
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.affiliation: Department of Epidemiology, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. Stephane.Heritier@monash.edu.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heritier
authors.affiliation: Department of Nephrology, Monash Medical Centre, Melbourne, VIC, Australia. Peter.Kerr@monash.edu.|Department of Medicine, Monash University, Melbourne, VIC, Australia. Peter.Kerr@monash.edu.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kerr
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. trevor.mori@uwa.edu.au.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.affiliation: Department of Surgery, Royal Melbourne Hospital, Melbourne, VIC, Australia. Amanda.Robertson@mh.org.au.
authors.forename: Amanda
authors.initials: A
authors.lastname: Robertson
authors.affiliation: Hospital Sultanah Aminah, Johor Bahru, Malaysia. laihooi@pd.jaring.my.
authors.forename: Hooi L
authors.initials: HL
authors.lastname: Seong
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. ashley.irish@health.wa.gov.au.|Department of Renal Medicine, Fiona Stanley Hospital, 102-118 Murdoch Drive, Murdoch, WA, 6150, Australia. ashley.irish@health.wa.gov.au.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Irish
mesh_terms: D001166:Arteriovenous Shunt, Surgical / Q000379:methods*; D001241:Aspirin / Q000627:therapeutic use*; D062905:Central Venous Catheters / Q000706:statistics & numerical data; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005395:Fish Oils / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D006435:Renal Dialysis / Q000379:methods*; D051436:Renal Insufficiency, Chronic / Q000628:therapy; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D010975:Platelet Aggregation Inhibitors; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor; D001241:Aspirin