Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12607000569404
Ethics application status
Approved
Date submitted
30/10/2007
Date registered
5/11/2007
Date last updated
4/06/2021
Date data sharing statement initially provided
4/06/2021
Date results information initially provided
4/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A placebo-controlled trial to assess the effect of aspirin and fish oil (omega-3 fatty acids) in the prevention of early thrombosis in arterio-venous fistulae in patients with chronic kidney disease requiring haemodialysis
Scientific title
A randomised, double-blind, placebo-controlled, factorial-design trial to assess the effect of aspirin and fish oil (omega-3 fatty acids) in the prevention of early thrombosis in arterio-venous fistulae in patients with Stage IV or V chronic kidney disease requiring haemodialysis
Secondary ID [1] 259874 0
AKTN 06.01
Secondary ID [2] 282495 0
EudraCT Number: 2009-014868-19
Universal Trial Number (UTN)
Trial acronym
FAVOURED Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early thrombosis in arterio-venous fistulae in patients with Stage IV or V chronic kidney disease requiring haemodialysis 2519 0
Condition category
Condition code
Renal and Urogenital 2614 2614 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study medication used is 4g Omega 3 fatty acid (4 1g capsules per day (46% eicosapentaenoic acid (EPA) and 38% docosapentaenoic acid (DHA)) and 100mg aspirin (1 100mg tablet per day). Participants can randomised to 6 arms;
1. Omega 3 fatty acid and aspirin,
2. Omega 3 fatty acid and aspirin placebo,
3. Omega 3 fatty acid placebo and aspirin,
4. Omega 3 fatty acid placebo and aspirin placebo,
5. Omega 3 fatty acid (participants already taking aspirin)
6. Omega 3 fatty acid placebo (participants already taking aspirin)
Participants start the study medication 24 hours prior to AVF surgery and contiune to 12 Week visit
Intervention code [1] 2246 0
Prevention
Comparator / control treatment
Placebo capsules matching to omega 3 fatty acid capsules and
placebo tablets matching to aspirin tablets
Control group
Placebo

Outcomes
Primary outcome [1] 3527 0
AVF Access Failure which is a composite of Thrombosis (absence of a thrill or bruit clinically and/or the requirement of Rescue Intervention), AVF Abandonment (permanent abandonment of study AVF) and Cannulation Failure (failure to successfully cannulate the study AVF in 8 or more of the 12 HD sessions during the Cannulation Assessment Period).
Cannulation Assessment Period (CAP) is based on when the patient commences maintenance haemodialysis (HD); If the participant starts HD prior to Week 12, the CAP starts from the first HD session after Week 12, if the partticipant start HD after Week 12, the CAP start at the first HD session.
Timepoint [1] 3527 0
Between Surgery and Month 12
Secondary outcome [1] 5896 0
Thrombosis (absence of a thrill or bruit clinically and/or the
requirement of Rescue Intervention)
Timepoint [1] 5896 0
12 months follow-up
Secondary outcome [2] 5897 0
Primary patency (presence of an audible bruit over the site of the arterio-venous anastomosis)
Timepoint [2] 5897 0
At 24 hrs, Weeks 1, 6 and 12, Month 6 and 12
Secondary outcome [3] 5898 0
Number and type of interventions (number and type of
interventions, both rescue and non-rescue, required by the study AVF)
Timepoint [3] 5898 0
12 months follow-up
Secondary outcome [4] 5899 0
Time to first Rescue intervention
Timepoint [4] 5899 0
Up to 12 Months
Secondary outcome [5] 302763 0
Time to AVF Abandonment
Timepoint [5] 302763 0
Month 12
Secondary outcome [6] 302764 0
Time to first cannulation
Timepoint [6] 302764 0
Up to 3 years
Secondary outcome [7] 302765 0
CVC Requirement
Timepoint [7] 302765 0
Up to Month 12
Secondary outcome [8] 302766 0
Days of CVC requirement
Timepoint [8] 302766 0
Up to Month 12
Secondary outcome [9] 302767 0
Adverse Event - All serious adverse events and adverse drug reactions (mainly bleeding events and gastrointestional symptoms) will be recorded from review of patient records and discussion with participants
Timepoint [9] 302767 0
Up to Month 6
Secondary outcome [10] 302768 0
Long term outcome of AVF (rate of permanent abandonment at Month 24 and 36 Visits and the time to permanent abandonment up to
Month 36 Visit)
Timepoint [10] 302768 0
Up to 3 Years
Secondary outcome [11] 302769 0
Cannulation Failure - failure to successfully cannulate the study AVF in 8 or more of the 12 HD sessions during the Cannulation Assessment Period (CAP). CAP is based on when the patient commences maintenance haemodialysis; If the participant starts HD prior to Week 12, the CAP starts from the first HD session after Week 12, if the partticipant start HD after Week 12, the CAP start at the first HD session.
Timepoint [11] 302769 0
Up to Month 12

Eligibility
Key inclusion criteria
1.Stage 4 or 5 chronic kidney disease
2.Currently on haemodialysis or haemodialysis is planned to start within 6 months (including patients currently on peritoneal dialysis).
3.Planned AVF will be the primary haemodialysis access mechanism.
4.Surgery to create an arterio-venous fistula in the upper or lower arm is planned.
5.Treating team agreeable to patient’s involvement in the trial
6.Informed consent
Minimum age
19 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Revision of existing AVF rather than de novo AVF 2.Medical indication for anti-platelet or thrombolytic agents other than aspirin 3.Known intolerance of agents including hypersensitivity to aspirin, allergy to any other NSAIDs or fish 4.Current use of omega-3 fatty acids within 4 weeks of commencing trial. 5.Pregnancy, lactation or intention to fall pregnant during the time course of the study 6.Known bleeding disorder or established diagnosis of active or suspected bleeding 7.History of GI ulcers or bleeding within the last 3 months 8.Platelet count less than 100 x 109 /L 9.Known active peptic ulcer disease 10.Severe hepatic insufficiency 11.Already receiving anti-coagulation therapy such as warfarin 12.Receiving regular non-steroidal anti-inflammatory (NSAIDS) agents for another indication such as arthritis 13.Syndrome of asthma, rhinitis and nasal polyps if uncontrolled on usual therapy 14.Plan to have other (non-access) surgery within 2 weeks of trial medication period 15.Potential non-compliance with treatment regimen in the view of the treating clinicians 16.Involved in another clinical trial where the intervention being trialled is likely to confound the outcome of this trial 17.Previously randomised to this trial

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each of the two interventions will be studied using a matching placebo, in order to make this a double-blind trial. At the completion of treatment, patients and investigators will be asked which treatment they believe the patient has been receiving, in order to have a measure of the degree of effectiveness of blinding. In addition, the primary outcome of AVF Access Failure will be made by an independent observer, unaware of the patient’s treatment assignment. Participants are centrally randomised using the online system Flexetrials
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be achieved using a permuted block method, balancing over the two stratification factors of 1) study site and 2) upper versus lower arm AVF
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Factorial
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The event rate for the primary outcome (AVF Access Failure)
is estimated to be 30% at twelve months in the control group. To achieve a 30% relative risk reduction is achievable with omega-3 fatty acids, then with 80% power and a significance level of 5%, 954 study subjects will be required. This allows for 5% drop-in from placebo to active treatment, 5% drop-out from study treatment (to no treatment – assumed equivalent to placebo), and 5% loss to follow-up. This is equivalent to an observed relative risk reduction of 24%. Without adjustment for compliance, the study size needed would have been 734 subjects.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/08/2008
Actual
21/08/2008
Date of last participant enrolment
Anticipated
31/01/2014
Actual
26/02/2014
Date of last data collection
Anticipated
Actual
4/09/2015
Sample size
Target
950
Accrual to date
Final
657
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 986 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 987 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 988 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [4] 989 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [5] 990 0
Gold Coast Hospital - Southport
Recruitment hospital [6] 991 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [7] 992 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [8] 993 0
Liverpool Hospital - Liverpool
Recruitment hospital [9] 994 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [10] 995 0
Prince of Wales Hospital - Randwick
Recruitment hospital [11] 996 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [12] 997 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [13] 998 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [14] 999 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [15] 1000 0
Royal Perth Hospital - Perth
Recruitment hospital [16] 1001 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [17] 1002 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [18] 1003 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [19] 1004 0
The Alfred - Prahran
Recruitment hospital [20] 1005 0
The Canberra Hospital - Garran
Recruitment hospital [21] 1006 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [22] 1007 0
The Townsville Hospital - Douglas
Recruitment hospital [23] 1008 0
Western Hospital - Footscray
Recruitment outside Australia
Country [1] 639 0
New Zealand
State/province [1] 639 0
Country [2] 640 0
Malaysia
State/province [2] 640 0
Country [3] 641 0
United Kingdom
State/province [3] 641 0

Funding & Sponsors
Funding source category [1] 2761 0
Government body
Name [1] 2761 0
NHMRC
Country [1] 2761 0
Australia
Funding source category [2] 287278 0
Commercial sector/Industry
Name [2] 287278 0
Abbott Products Operations AG
Country [2] 287278 0
Switzerland
Funding source category [3] 287279 0
Commercial sector/Industry
Name [3] 287279 0
Amgen Australia Pty Ltd
Country [3] 287279 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Kidney Trials Network
Address
School of Population Health
University of Queensland
Princess Alexandra Hospital
Ipwich Rd
Wolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 2494 0
None
Name [1] 2494 0
Address [1] 2494 0
Country [1] 2494 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4681 0
Royal Perth Hospital Ethics Committee
Ethics committee address [1] 4681 0
Royal Perth Hospital
Wellington Street Campus
GPO Box X2213
Perth WA 6847
Ethics committee country [1] 4681 0
Australia
Date submitted for ethics approval [1] 4681 0
Approval date [1] 4681 0
10/01/2007
Ethics approval number [1] 4681 0
Ref: EC 2007/067

Summary
Brief summary
FAVOURED is a multicentre, randomised controlled trial design. The objectives of this trial are to determine whether the use of the omega-3 fatty acids and to a lesser extent, aspirin, will effectively improve postsurgical outcomes for patients with de novo arterio-venous fistulae (AVF). The study population are patients with stage IV or V chronic kidney disease who require or will require haemodialysis and who are scheduled to undergo creation of an AVF. The primary outcome is AVF Access Failure, which is a composite of Thrombosis, AVF Abandonment, and Cannulation Failure during the Cannulation Assessment Period. Secondary outcomes include AVF access failure according to strata of aspirin use, safety and adverse events of omega-3 fatty acids and aspirin alone or in combination, catheter use, and rescue interventions.
Trial website
www.aktn.org.au
Trial related presentations / publications
Preventing AVF Thrombosis: The rationale and design of the Omega-3 fatty Acids (Fish Oils) and Aspirin in Vascular Outcomes in Renal Disease (FAVOURED) study. Irish A, Dogra G, Mori T et al. BMC Nephrology 2009 Jan 21; 10(1): 1 Epub.
Public notes

Contacts
Principal investigator
Name 28157 0
Dr Ashley Irish
Address 28157 0
Renal Unit, Royal Perth Hospital GPO Box X2213 Perth WA
6001
Country 28157 0
Australia
Phone 28157 0
61 8 9224 2244
Fax 28157 0
Email 28157 0
Ashley.Irish@health.wa.gov.au
Contact person for public queries
Name 11314 0
Ms Peta-Anne Paul-Brent
Address 11314 0
Australasian Kidney Trials Network, Centre for Health Services Research
Faculty of Medicine, The University of Queensland
Level 5, Translational Research Institute
37 Kent Street, Woolloongabba
Brisbane Qld 4102 Australia
Country 11314 0
Australia
Phone 11314 0
+61 7 3443 5463
Fax 11314 0
07 3176 5663
Email 11314 0
p.kerr@uq.edu.au
Contact person for scientific queries
Name 2242 0
Ms Peta-Anne Paul-Brent
Address 2242 0
Australasian Kidney Trials Network, Centre for Health Services Research
Faculty of Medicine, The University of Queensland
Level 5, Translational Research Institute
37 Kent Street, Woolloongabba
Brisbane Qld 4102 Australia
Country 2242 0
Australia
Phone 2242 0
+61 7 3443 5463
Fax 2242 0
07 3176 5663
Email 2242 0
p.kerr@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11912Statistical analysis plan https://aktn.org.au/favoured 



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 10.1001/jamainternmed.2016.8029

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis a randomized clinical trial.2017https://dx.doi.org/10.1001/jamainternmed.2016.8029
EmbaseArteriovenous access failure, stenosis, and thrombosis.2016https://dx.doi.org/10.1177/2054358116669126
EmbaseThe 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.2015https://dx.doi.org/10.1186/s12882-015-0089-2
Dimensions AIPreventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study2009https://doi.org/10.1186/1471-2369-10-1
N.B. These documents automatically identified may not have been verified by the study sponsor.