BackgroundTrials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to determine if daily fluoxetine for 6 months after stroke improves functional outcome in Australasian and Vietnamese patients. MethodsAFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial conducted in 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10). Eligible patients were adults with a clinical diagnosis of stroke in the previous 2-15 days and a persisting neurological deficit. Patients were randomised via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20mg or matching placebo for 6 months. Patients, investigators and outcome assessors were masked to the treatment allocation. The primary outcome was functional outcome, measured by the modified Rankin scale (mRS), at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Analyses were according to the patient's treatment allocation. The trial is registered with the ACTRN registry, number 12611000774921. FindingsPowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation 1280 patients were recruited in Australia (n=532), New Zealand (n=42) and Vietnam (n=706) between 11 January 2013 and 30 June 2019; 642 were allocated fluoxetine and 638 placebo. Adherence to trial medication (mean 167 [SD 48] days) was similar between groups. At 6 months, mRS data were available in 624 (97.2%) patients allocated fluoxetine and 632 (99.1%) placebo. The distribution of mRS categories at 6 months was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0.936, 95% CI 0.762-1.150; p=0.53), and consistent among all pre-defined subgroups. Compared to placebo, patients allocated fluoxetine had more falls (20 [3.12%] vs 7 [1.10%]; p=0.02), bone fractures (19 [2•96%] vs 6 [0.94%]; p=0.01) and epileptic seizures (10 [1.56%] vs 2 [0.31%]; p=0.04) at 6 months. InterpretationFluoxetine 20mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. These results do not support the use of fluoxetine to improve outcome after stroke.

Background and purpose: ''Take Charge'' is a novel, community-based self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. In a previous randomized controlled trial, a single Take Charge session improved independence and health-related quality of life 12 months following stroke in M aori and Pacific New Zealanders. We tested the same intervention in three doses (zero, one, or two sessions) in a larger study and in a broader non-M aori and non-Pacific population with stroke. We aimed to confirm whether the Take Charge intervention improved quality of life at 12 months after stroke in a different population and whether two sessions were more effective than one. Methods:We randomized 400 people within 16 weeks of acute stroke who had been discharged to institution-free community living at seven centers in New Zealand to a single Take Charge session (TC1, n ¼ 132), two Take Charge sessions six weeks apart (TC2, n ¼ 138), or a control intervention (n ¼ 130). Take Charge is a ''talking therapy'' that encourages a sense of purpose, autonomy, mastery, and connectedness with others. The primary outcome was the Physical Component Summary score of the Short Form 36 at 12 months following stroke comparing any Take Charge intervention to control.Results: Of the 400 people randomized (mean age 72.2 years, 58.5% male), 10 died and two withdrew from the study. The remaining 388 (97%) people were followed up at 12 months after stroke. Twelve months following stroke, participants in either of the TC groups (i.e. TC1 þ TC2) scored 2.9 (95% confidence intervals (CI) 0.95 to 4.9, p ¼ 0.004) points higher (better) than control on the Short Form 36 Physical Component Summary. This difference remained significant when adjusted for pre-specified baseline variables. There was a dose effect with Short Form 36 Physical Component Summary scores increasing by 1.9 points (95% CI 0.8 to 3.1, p < 0.001) for each extra Take Charge session received. Exposure to the Take Charge intervention was associated with reduced odds of being dependent (modified Rankin Scale 3 to 5) at 12 months (TC1 þ TC2 12% versus control 19.5%, odds ratio 0.55, 95% CI 0.31 to 0.99, p ¼ 0.045). Conclusions:Confirming the previous randomized controlled trial outcome, Take Charge-a low-cost, personcentered, self-directed rehabilitation intervention after stroke-improved health-related quality of life and independence.Clinical trial registration-URL: http://www.anzctr.org.au. Unique identifier: ACTRN12615001163594

Objective: To use secondary data from the Taking Charge after Stroke study to explore mechanisms for the positive effect of the Take Charge intervention on physical health, advanced activities of daily living and independence for people after acute stroke. Design: An open, parallel-group, randomised trial with two active and one control intervention and blinded outcome assessment. Setting: Community. Participants: Adults ( n = 400) discharged to community, non-institutional living following acute stroke. Interventions: One, two, or zero sessions of the Take Charge intervention, a self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. Measures: Twelve months after stroke: Mood (Patient Health Questionnaire-2, Mental Component Summary of the Short Form 36); ‘ability to Take Charge’ using a novel measure, the Autonomy-Mastery-Purpose-Connectedness (AMP-C) score; activation (Patient Activation Measure); body mass index (BMI), blood pressure (BP) and medication adherence (Medication Adherence Questionnaire). Results: Follow-up was near-complete (388/390 (99.5%)) of survivors at 12 months. Mean age (SD) was 72.0 (12.5) years. There were no significant differences in mood, activation, ‘ability to Take Charge’, medication adherence, BMI or BP by randomised group at 12 months. There was a significant positive association between baseline AMP-C scores and 12-month outcome for control participants (1.73 (95%CI 0.90 to 2.56)) but not for the Take Charge groups combined (0.34 (95%CI −0.17 to 0.85)). Conclusion: The mechanism by which Take Charge is effective remains uncertain. However, our findings support a hypothesis that baseline variability in motivation, mastery and connectedness may be modified by the Take Charge intervention.

IntroductionStroke is one of the leading causes of disability worldwide. Recent data support the possibility that person-centred, self-management interventions can reduce dependence after stroke. However, there is limited information on the generalisability and optimum dose of these interventions.MethodsThe Taking Charge After Stroke (TaCAS) study is a multicentre, investigator-blinded, randomised controlled trial recruiting 400 participants following acute stroke from seven hospitals in New Zealand. All patients discharged to community living who have ongoing symptoms at time of discharge (modified Rankin scale>0) will be eligible. Participants will be randomly assigned to one Take Charge session, two Take Charge sessions 6 weeks apart or control.OutcomesThe primary outcome will be the Physical Component Summary score of the Short-Form 36 at 12 months post stroke. Secondary outcomes will include dependence (modified Rankin scale), performance in activities of daily living (Barthel Index) and carer strain (Caregiver Strain Index), at 6 and 12 months post stroke. All analyses will be conducted on an intention-to-treat basis.Ethics and disseminationThe TaCAS study is funded by a Health Research Council of New Zealand grant. It has been approved by the Central Health and Disability Ethics Committee (15/CEN/115). Results will be published and presented at relevant stroke meetings within New Zealand and internationally, informing the use of a self-management intervention after stroke.Trial registrationAustralia and New Zealand Clinical Trials Registry ACTRN12615001163594. Date registered 02-11-2015. Medical Research Institute of New Zealand Registry TCS01. Universal trial number U1111-1171-4127.

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