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Trial registered on ANZCTR


Registration number
ACTRN12611000774921
Ethics application status
Approved
Date submitted
22/07/2011
Date registered
22/07/2011
Date last updated
17/02/2021
Date data sharing statement initially provided
17/12/2018
Date results provided
17/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial
Scientific title
An Australasian, investigator-driven, NHMRC funded, multicentre, prospective randomised, parallel group, double-blind, placebo-controlled trial to establish the effect(s) of routine administration of fluoxetine (20mg once daily) in patients with recent stroke.
Secondary ID [1] 262683 0
Nil
Universal Trial Number (UTN)
Trial acronym
AFFINITY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 268386 0
Condition category
Condition code
Stroke 268526 268526 0 0
Haemorrhagic
Stroke 268525 268525 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fluoxetine (20mg once daily) for 6 months via oral capsule or enteral tube.
Intervention code [1] 267027 0
Treatment: Drugs
Comparator / control treatment
Placebo capsule taken once daily for 6 months
Control group
Placebo

Outcomes
Primary outcome [1] 269272 0
Functional outcome as measured by the mRS using the simplified modified Rankin Scale questionnaire (smRSq) at 180 days after randomisation
Timepoint [1] 269272 0
Baseline, 1 month, 3 months, 6 months, 12 months
Secondary outcome [1] 355057 0
New Stroke, ischaemic or haemorrhagic [ not the qualifying event leading to enrolment]
Assessed by Clinical presentation of the participant assessed by the treating clinician / CT scan / MRI scan / study specific questionnaire / medical records
Timepoint [1] 355057 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [2] 355063 0
Epileptic seizure [ Focal or generalised }
Assessed by study specific questionnaire / medical records
Timepoint [2] 355063 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [3] 279254 0
overall health status (Stoke Impact Scale)
Timepoint [3] 279254 0
6 months, 12 months
Secondary outcome [4] 355059 0
Upper gastrointestinal bleed requiring blood transfusion and /or endoscopy
Assessed by study specific questionnaire / medical records
Timepoint [4] 355059 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [5] 355053 0
Mood (Patient Health Questionnaire - 9 item {PHQ-9}
Timepoint [5] 355053 0
Baseline, 1 month, 3 months, 6 months, 12 months
Secondary outcome [6] 355061 0
Fall resulting in injury
Assessed by study specific questionnaire / medical records
Timepoint [6] 355061 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [7] 279253 0
New diagnosis of depression requiring treatment with antidepressants.
Assessed using Patient Health Questionnaire (PHQ-9)
Timepoint [7] 279253 0
Baseline, 1 month, 3 months, 6 months, 12 months
Secondary outcome [8] 279255 0
cognition (TICSm)
Timepoint [8] 279255 0
6 months, 12 months
Secondary outcome [9] 279260 0
adherence to trial medication (patient self report of medication compliance & tablet counting)
Timepoint [9] 279260 0
1 month, 3 months, 6 months
Secondary outcome [10] 279256 0
Health-Related Quality of Life (HRQoL) [EQ-5D-5L)
Timepoint [10] 279256 0
6 months, 12 months
Secondary outcome [11] 355054 0
Communication (Stroke Impact Scale {SIS}
Timepoint [11] 355054 0
6 months , 12 months
Secondary outcome [12] 355052 0
survival
Timepoint [12] 355052 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [13] 355056 0
Functional ability Simplified Modified Rankin Scale (smRSq)
Timepoint [13] 355056 0
6 months, 12 months
Secondary outcome [14] 355067 0
Attempted suicide / self harm
Assessed by study specific questionnaire / medical records
Timepoint [14] 355067 0
1 month, 3months, 6 months, 12 months
Secondary outcome [15] 279259 0
health care utilisation (Data linkage to patient medical records and patient diary recording hospital admissions/ visits & GP/specialist visits)
Timepoint [15] 279259 0
6 months, 12 months
Secondary outcome [16] 355058 0
Acute coronary syndrome [Myocardial infarction confirmed by ECG and / or raised serum Troponin. Assessed by Electrocardiogram / serum assay [raised serum troponin / study specific questionnaire / medical records
Timepoint [16] 355058 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [17] 355065 0
Symptomatic hyperglycaemia { blood sugar > 22mmol/L
Assessed by study specific questionnaire / medical records
Timepoint [17] 355065 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [18] 355055 0
Motor Function (Stroke Impact Scale [SIS] )
Timepoint [18] 355055 0
6 months, 12 months
Secondary outcome [19] 279258 0
fatigue (vitality of subscale of SF36)
Timepoint [19] 279258 0
6 months, 12 months
Secondary outcome [20] 355060 0
Other major bleed ( i.e not upper GI or intracerebral ) requiring blood transfusion or procedural intervention. Assessed by study specific questionnaire / medical records
Timepoint [20] 355060 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [21] 355062 0
New Fracture [confirmed on X ray}
Timepoint [21] 355062 0
1 month , 3 months, 6 months, 12 months
Secondary outcome [22] 391995 0
Functional outcome as measured by the mRS using the simplified modified Rankin Scale questionnaire (smRSq) in two predefined geographical subgroups - a) participants recruited in Australia and New Zealand (ANZ), and b) participants recruited in Vietnam.
Timepoint [22] 391995 0
180 days after randomisation
Secondary outcome [23] 355064 0
Symptomatic hypoglycaemia [blood sugar < 3mmol/L }
Assessed by study specific questionnaire / medical records
Timepoint [23] 355064 0
1 month, 3 months, 6 months, 12 months
Secondary outcome [24] 355066 0
New hyponatremia [Na < 125mmol/L
Assessed by study specific questionnaire / medical records
Timepoint [24] 355066 0
1 month, 3 months, 6 months, 12 months

Eligibility
Key inclusion criteria
Men or women aged 18 years or more with: - Clinical diagnosis of stroke 2-15 days previously (Day of stroke onset = Day 0, randomise on Day 2-15); - Brain imaging consistent with ischaemic or haemorrhagic (intracerebral and/or subarachnoid) stroke (including normal CT brain scan); - Persisting measurable focal neurological deficits (e.g. motor, somatosensory, visual, language, cognitive) present at randomisation and severe enough to produce a modified Rankin Scale (mRS) score of equal or > 1 and to warrant treatment from the perspective of patient or carer(s).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
Any of the following:
History of epileptic seizures
History of bipolar disorder
History of drug overdose or attempted suicide
Ongoing treatment with any selective serotonin reuptake inhibitor (SSRI)
Allergy or contra indication to fluoxetine including
Hepatic impairment (serum alanine aminotransferase [ALT] >120 U/l),
Renal impairment (creatinine >180micromol/l or eGFR < 30ml/min/1.73m2),
Hyponatremia (sodium <125mmol/L) despite treatment of the cause and confirmed on repeat testing,
Use of medications that may interact seriously with fluoxetine
Proposed use of a monoamine oxidase inhibitor (MAOI), or use of a MAOI within 14 days prior to randomisation
Current treatment with an antipsychotic drug (neuroleptic), pimozide, tamoxifen, or tramadol, unless the patient, doctor and if possible prescribing doctor, believe it is appropriate to discontinue use.
Not available for follow up over the next 365 days e.g. no fixed home address.
Life-threatening illness (e.g. advanced cancer) that is likely to reduce 365 day survival
Pregnant, breast-feeding or of child-bearing potential and not using contraception
Enrolled in another interventional clinical research trial involving an investigational product (medicine) or device

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
to jointly present the results of the trial along with our sister trial "EFFECTS" in Sweden which had completed its recruitment target.
Date of first participant enrolment
Anticipated
20/09/2012
Actual
11/01/2013
Date of last participant enrolment
Anticipated
31/12/2019
Actual
28/06/2019
Date of last data collection
Anticipated
31/12/2020
Actual
3/08/2020
Sample size
Target
1600
Accrual to date
Final
1280
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 1670 0
Swan Districts Hospital - Middle Swan
Recruitment hospital [2] 12746 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [3] 1668 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 1669 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 2926 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [6] 12732 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [7] 12734 0
Footscray Hospital - Footscray
Recruitment hospital [8] 12736 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [9] 2922 0
Rockingham General Hospital - Cooloongup
Recruitment hospital [10] 1671 0
Osborne Park Hospital - Stirling
Recruitment hospital [11] 12745 0
Prince of Wales Private Hospital - Randwick
Recruitment hospital [12] 2925 0
Blacktown Hospital - Blacktown
Recruitment hospital [13] 2932 0
Wagga Wagga Base Hospital - Wagga Wagga
Recruitment hospital [14] 12733 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [15] 2923 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [16] 2927 0
Camden Hospital - Camden
Recruitment hospital [17] 2924 0
Western Hospital - Footscray
Recruitment hospital [18] 12740 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment hospital [19] 12730 0
Belmont Hospital - Belmont
Recruitment hospital [20] 2928 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [21] 2929 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [22] 12738 0
Shoalhaven Hospital - Nowra
Recruitment hospital [23] 12743 0
Liverpool Hospital - Liverpool
Recruitment hospital [24] 2930 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [25] 12795 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [26] 12741 0
Caulfield Hospital - Caulfield
Recruitment hospital [27] 12731 0
Calvary Public Hospital ACT - Bruce
Recruitment hospital [28] 2933 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [29] 12744 0
Manly Hospital - Manly
Recruitment hospital [30] 12737 0
St John of God Midland Public Hospital - Midland
Recruitment hospital [31] 12742 0
John Hunter Hospital - New Lambton
Recruitment hospital [32] 12735 0
Kingston Centre - Cheltenham
Recruitment hospital [33] 12739 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 25164 0
3192 - Cheltenham
Recruitment postcode(s) [2] 25163 0
6150 - Murdoch
Recruitment postcode(s) [3] 25170 0
3162 - Caulfield
Recruitment postcode(s) [4] 25161 0
2617 - Bruce
Recruitment postcode(s) [5] 25165 0
5112 - Elizabeth Vale
Recruitment postcode(s) [6] 25160 0
2280 - Belmont
Recruitment postcode(s) [7] 25162 0
2298 - Waratah
Recruitment postcode(s) [8] 25166 0
6056 - Midland
Recruitment postcode(s) [9] 25171 0
2305 - New Lambton
Recruitment postcode(s) [10] 25174 0
2031 - Randwick
Recruitment postcode(s) [11] 25168 0
3021 - St Albans
Recruitment postcode(s) [12] 25173 0
2095 - Manly
Recruitment postcode(s) [13] 25167 0
2541 - Nowra
Recruitment postcode(s) [14] 25169 0
3350 - Ballarat Central
Recruitment postcode(s) [15] 25172 0
2170 - Liverpool
Recruitment postcode(s) [16] 25255 0
2200 - Bankstown
Recruitment postcode(s) [17] 25175 0
4020 - Redcliffe
Recruitment outside Australia
Country [1] 21132 0
Viet Nam
State/province [1] 21132 0
Country [2] 6320 0
New Zealand
State/province [2] 6320 0
North Island

Funding & Sponsors
Funding source category [1] 267504 0
Government body
Name [1] 267504 0
National Health and Medical Research Council
Country [1] 267504 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue
Nedlands
Perth, Western Australia
6009
Country
Australia
Secondary sponsor category [1] 266546 0
Other
Name [1] 266546 0
The George Institute for Global Health
Address [1] 266546 0
PO Box M201
Missenden Road NSW 2050
Country [1] 266546 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302202 0
Alfred Health
Ethics committee address [1] 302202 0
Ethics committee country [1] 302202 0
Australia
Date submitted for ethics approval [1] 302202 0
21/07/2016
Approval date [1] 302202 0
19/08/2016
Ethics approval number [1] 302202 0
248/16
Ethics committee name [2] 302204 0
Southern Adelaide Local Health Network
Ethics committee address [2] 302204 0
Ethics committee country [2] 302204 0
Australia
Date submitted for ethics approval [2] 302204 0
09/12/2014
Approval date [2] 302204 0
09/01/2015
Ethics approval number [2] 302204 0
275.14 HREC/14/SAC/284
Ethics committee name [3] 269469 0
HREC Royal Perth Hospital
Ethics committee address [3] 269469 0
Ethics committee country [3] 269469 0
Australia
Date submitted for ethics approval [3] 269469 0
31/08/2011
Approval date [3] 269469 0
24/02/2012
Ethics approval number [3] 269469 0
2011/131
Ethics committee name [4] 302203 0
St John Of God Health Care
Ethics committee address [4] 302203 0
Ethics committee country [4] 302203 0
Australia
Date submitted for ethics approval [4] 302203 0
30/10/2015
Approval date [4] 302203 0
16/02/2016
Ethics approval number [4] 302203 0
894
Ethics committee name [5] 291589 0
Western Sydney Local Health District
Ethics committee address [5] 291589 0
Ethics committee country [5] 291589 0
Australia
Date submitted for ethics approval [5] 291589 0
Approval date [5] 291589 0
30/04/2013
Ethics approval number [5] 291589 0
HREC2013/3/4.1(3619)AU RED HREC/13/WMEAD/165
Ethics committee name [6] 302201 0
Calvary Health Care Bruce
Ethics committee address [6] 302201 0
Ethics committee country [6] 302201 0
Australia
Date submitted for ethics approval [6] 302201 0
30/09/2014
Approval date [6] 302201 0
07/04/2015
Ethics approval number [6] 302201 0
29-2014

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32909 0
Prof Graeme Hankey
Address 32909 0
Faculty of Health and Medical Sciences
Medical School
QEII Medical Centre Unit (M503)
The University of Western Australia
Level 2, Harry Perkins Institute of Medical Research
6 Verdun Street
NEDLANDS WA 6009
Country 32909 0
Australia
Phone 32909 0
+61 8 6151 1061
Fax 32909 0
Email 32909 0
graeme.hankey@uwa.edu.au
Contact person for public queries
Name 16156 0
Anne Claxton
Address 16156 0
Faculty of Health and Medical Sciences
Medical School
QEII Medical Centre Unit (M503)
The University of Western Australia
Level 2, Harry Perkins Institute of Medical Research
6 Verdun Street
NEDLANDS WA 6009
Country 16156 0
Australia
Phone 16156 0
+61 8 6151 1061
Fax 16156 0
Email 16156 0
anne.claxton@health.wa.gov.au
Contact person for scientific queries
Name 7084 0
Graeme Hankey
Address 7084 0
Faculty of Health and Medical Sciences
Medical School
QEII Medical Centre Unit (M503)
The University of Western Australia
Level 2, Harry Perkins Institute of Medical Research
6 Verdun Street
NEDLANDS WA 6009
Country 7084 0
Australia
Phone 7084 0
+61 8 6151 1061
Fax 7084 0
Email 7084 0
graeme.hankey@uwa.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?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 343231-(Uploaded-02-03-2021-14-45-34)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AISelective Serotonin Reuptake Inhibitors for Stroke Recovery2013https://doi.org/10.1001/jama.2013.107828
EmbaseThe FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: A study protocol for three multicentre randomised controlled trials.2015https://dx.doi.org/10.1186/s13063-015-0864-1
EmbaseThe FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: Statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis.2017https://dx.doi.org/10.1186/s13063-017-2385-6
EmbaseSafety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial.2020https://dx.doi.org/10.1016/S1474-4422%2820%2930207-6
EmbaseUpdate to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical analysis plan for the trials and for the individual patient data meta-analysis.2020https://dx.doi.org/10.1186/s13063-020-04875-1
EmbaseDepression Outcomes among Patients Treated with Fluoxetine for Stroke Recovery: The AFFINITY Randomized Clinical Trial.2021https://dx.doi.org/10.1001/jamaneurol.2021.2418
EmbaseCognitive Impairment After Stroke and Treatment With Fluoxetine: A Planned Analysis of the AFFINITY Randomized Controlled Trial.2022https://dx.doi.org/10.1016/j.jagp.2022.08.002
EmbaseMeasures Associated with Early, Late, and Persistent Clinically Significant Symptoms of Depression 1 Year after Stroke in the AFFINITY Trial.2022https://dx.doi.org/10.1212/WNL.0000000000200058
EmbaseRepeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings.2022https://dx.doi.org/10.1161/JAHA.121.025425
EmbaseWishing to die or self-harm after stroke: A planned secondary analysis of the AFFINITY Randomised Controlled Trial.2022https://dx.doi.org/10.1016/j.maturitas.2022.08.011
N.B. These documents automatically identified may not have been verified by the study sponsor.