ANZCTR - Registration

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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 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]

AKTN 06.01

Secondary ID [2]

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

Condition category

Condition code

Renal and Urogenital

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]

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]

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]

Between Surgery and Month 12

Secondary outcome [1]

Thrombosis (absence of a thrill or bruit clinically and/or the
requirement of Rescue Intervention)

Timepoint [1]

12 months follow-up

Secondary outcome [2]

Primary patency (presence of an audible bruit over the site of the arterio-venous anastomosis)

Timepoint [2]

At 24 hrs, Weeks 1, 6 and 12, Month 6 and 12

Secondary outcome [3]

Number and type of interventions (number and type of
interventions, both rescue and non-rescue, required by the study AVF)

Timepoint [3]

12 months follow-up

Secondary outcome [4]

Time to first Rescue intervention

Timepoint [4]

Up to 12 Months

Secondary outcome [5]

Time to AVF Abandonment

Timepoint [5]

Month 12

Secondary outcome [6]

Time to first cannulation

Timepoint [6]

Up to 3 years

Secondary outcome [7]

CVC Requirement

Timepoint [7]

Up to Month 12

Secondary outcome [8]

Days of CVC requirement

Timepoint [8]

Up to Month 12

Secondary outcome [9]

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]

Up to Month 6

Secondary outcome [10]

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]

Up to 3 Years

Secondary outcome [11]

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]

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?

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]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

Concord Repatriation Hospital - Concord

Recruitment hospital [3]

Fremantle Hospital and Health Service - Fremantle

Recruitment hospital [4]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [5]

Gold Coast Hospital - Southport

Recruitment hospital [6]

Greenslopes Private Hospital - Greenslopes

Recruitment hospital [7]

John Hunter Hospital Royal Newcastle Centre - New Lambton

Recruitment hospital [8]

Liverpool Hospital - Liverpool

Recruitment hospital [9]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [10]

Prince of Wales Hospital - Randwick

Recruitment hospital [11]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [12]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [13]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [14]

Royal North Shore Hospital - St Leonards

Recruitment hospital [15]

Royal Perth Hospital - Perth

Recruitment hospital [16]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [17]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [18]

Sydney Adventist Hospital - Wahroonga

Recruitment hospital [19]

The Alfred - Prahran

Recruitment hospital [20]

The Canberra Hospital - Garran

Recruitment hospital [21]

Toowoomba Hospital - Toowoomba

Recruitment hospital [22]

The Townsville Hospital - Douglas

Recruitment hospital [23]

Western Hospital - Footscray

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Country [2]

Malaysia

State/province [2]

Country [3]

United Kingdom

State/province [3]

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Funding source category [2]

Commercial sector/Industry

Name [2]

Abbott Products Operations AG

Address [2]

Hegenheimermattweg 127 4123 Allschwil Switzerland

Country [2]

Switzerland

Funding source category [3]

Commercial sector/Industry

Name [3]

Amgen Australia Pty Ltd

Address [3]

Level 7, 123 Epping Road North Ryde NSW
2113

Country [3]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Perth Hospital Ethics Committee

Ethics committee address [1]

Royal Perth Hospital
Wellington Street Campus
GPO Box X2213
Perth WA 6847

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

10/01/2007

Ethics approval number [1]

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

Dr Ashley Irish

Address

Renal Unit, Royal Perth Hospital GPO Box X2213 Perth WA
6001

Country

Australia

Phone

61 8 9224 2244

Fax

[email protected]

Contact person for public queries

Name

Peta-Anne Paul-Brent

Address

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

Australia

Phone

+61 7 3443 5463

Fax

07 3176 5663

[email protected]

Contact person for scientific queries

Name

Peta-Anne Paul-Brent

Address

Country

Australia

Phone

+61 7 3443 5463

Fax

07 3176 5663

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
11912	Statistical analysis plan		https://aktn.org.au/favoured

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	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	2009	https://doi.org/10.1186/1471-2369-10-1
Embase	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.	2015	https://dx.doi.org/10.1186/s12882-015-0089-2
Embase	Arteriovenous access failure, stenosis, and thrombosis.	2016	https://dx.doi.org/10.1177/2054358116669126
Embase	Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis a randomized clinical trial.	2017	https://dx.doi.org/10.1001/jamainternmed.2016.8029

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically