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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.

Viecelli AK, Pascoe E, Polkinghorne KR, Hawley C, Paul-Brent PA, Badve SV, Cass A, Heritier S, Kerr PG, Mori TA, Robertson A, Seong HL, Irish AB, FAVOURED study te - BMC Nephrol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia. andrea.viecelli@health.qld.gov.au.

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).

No MeSH data available.


Related in: MedlinePlus

Amended study protocol
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Fig1: Amended study protocol

Mentions: The original protocol was a 2x2 factorial-design trial, where participants were randomised to one of four treatment groups formed by aspirin or matching placebo and omega-3 PUFAs or matching placebo. Patients who were not taking aspirin or who were able to cease taking aspirin were consented and randomised to one of the 4 groups. The study protocol was amended in June 2011 to include suitable patients who were on aspirin at the time of screening and were unable to cease. In this expanded study protocol, participants were allowed to continue with open-label aspirin and were randomised to omega-3 PUFAs or matched placebo only (Fig. 1). The rationale behind this study amendment will be described further in the discussion. Randomisation was achieved using a minimisation method to balance treatments over two stratification factors: study site and AVF location (upper versus lower arm).Fig. 1


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.

Viecelli AK, Pascoe E, Polkinghorne KR, Hawley C, Paul-Brent PA, Badve SV, Cass A, Heritier S, Kerr PG, Mori TA, Robertson A, Seong HL, Irish AB, FAVOURED study te - BMC Nephrol (2015)

Amended study protocol
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482267&req=5

Fig1: Amended study protocol
Mentions: The original protocol was a 2x2 factorial-design trial, where participants were randomised to one of four treatment groups formed by aspirin or matching placebo and omega-3 PUFAs or matching placebo. Patients who were not taking aspirin or who were able to cease taking aspirin were consented and randomised to one of the 4 groups. The study protocol was amended in June 2011 to include suitable patients who were on aspirin at the time of screening and were unable to cease. In this expanded study protocol, participants were allowed to continue with open-label aspirin and were randomised to omega-3 PUFAs or matched placebo only (Fig. 1). The rationale behind this study amendment will be described further in the discussion. Randomisation was achieved using a minimisation method to balance treatments over two stratification factors: study site and AVF location (upper versus lower arm).Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia. andrea.viecelli@health.qld.gov.au.

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).

No MeSH data available.


Related in: MedlinePlus