FOCUS: Fluoxetine Or Control Under Supervision. Gillian Mead and Martin Dennis Co-chief investigators, on behalf of the FOCUS team

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1 FOCUS: Fluoxetine Or Control Under Supervision Gillian Mead and Martin Dennis Co-chief investigators, on behalf of the FOCUS team

2 Background Several small trials suggest a benefit of SSRI in prevention of post-stroke depression and to improve recovery FLAME trial (n=118) demonstrated improvements in motor recovery and mrs at 3/12 if given fluoxetine days 5-15 after stroke onset FLAME ignited world-wide interest in the role of SSRI for stroke recovery, through mechanisms other than just an effect on mood

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4 Cochrane review of SSRI for 52 trials, 4059 patients stroke recovery Fluoxetine most commonly used SSRI At end of treatment, there were improvements in But Dependency, disability, neurological impairment, anxiety and depression Multiple sources of biases in the trials Most were small There was heterogeneity in estimates of treatment effect Most did not follow up patients after treatment had ended Larger trials are needed Mead GE, Hsieh C-F, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, Hackett ML. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database of Systematic Reviews 2012 Issue 11.

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7 Aims of FOCUS To determine whether taking fluoxetine 20mg each day for 6 months after stroke Reduces dependency after stroke Reduces other post-stroke problems Whether any improvements persist after the treatment has stopped To provide robust evidence about whether any benefits outweigh any risks Target recruitment: 3000

8 Inclusion criteria Clinically definite stroke (ischaemic or haemorrhagic) Persisting deficits at time of joining the study, that are considered severe enough to warrant treatment with the FOCUS medication Between 2 and 15 days after stroke Main exclusions-contraindications to SSRI

9 Outcome measures Primary: modified Rankin score Secondary Survival Euroquol 5-D Vitality score of SF-36 Stroke impact score (59 items, 8 domains) New clinical diagnosis of depression Resource use

10 Eligible consenting patients (total 3000) Collect baseline data Randomise Fluoxetine 20mg for 6/12 Placebo for 6/12 Discharge (for IP) or 1 month central follow up (for OP) Adverse effects and adherence 3 month central postal reminder 6 months Central follow up (Postal / telephone / web) Modified Rankin scale (primary outcome) and secondary outcomes 12 months Central follow-up (Postal / telephone / web) Primary and secondary outcomes Patient flagged with national statistics for death certificate

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13 Feasibility Remote start up and close out meetings Can recruit inpatient or outpatients Stroke research nurses can recruit (need doctor to confirm eligibility and prescribe trial medication) Simple intervention no funding required Simple data collection form at discharge Few SAEs need to be reported Central follow up after hospital discharge

14 15 centres Progress so far Exeter is the 5 th highest recruiting centre 86 patients ( ) All 6 patients reaching 6 month follow-up have sent back complete follow-up questionnaires No serious adverse events reported

15 What proportion of patients might be eligible? At one site, we screened 276 admissions to hospital with stroke ( to ) Of these 93 (34%) were eligible Most common reasons for exclusion Stroke deficits too mild (65), on SSRI (24), history of seizures (15), renal impairment (15) 82 were approached and 30 consented Most did not give reasons for refusals, but of those that did, fears about side effects and not wanting more drugs were most common (14)

16 Next stages Over the next year, we aim to recruit additional centres New drug/placebo on order We will send out Expressions Of Interest forms by 1 st May 2013 via the SRN Centres to return EOI forms In start-up phase (to August 2014) our aim was to recruit 200 patients. We should exceed this. Funding application for main phase to be submitted to HTA in May Main phase will run October 2014 to September 2018

17 For further information Visit our website (