StrokePhase 3EFFECTSNCT02683213
Efficacy of Fluoxetine - a Trial in Stroke
A Phase 3 study testing Fluoxetine in people with Stroke, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
The purpose of this study is to investigate whether routine administration of fluoxetine 20mg once daily in the 6 months initiated during the acute stroke improves the patient's functional outcome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Fluoxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,500 participants
- Where
- 1 siteSweden
- Study dates
- 20 Oct 2014to Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent can only be obtained from a patient who according to the trial investigator is mentally capable of decision-making and who, after having received information and got answers to their questions, wants to participate in the trial.
- Brain imaging is compatible with intra cerebral hemorrhage or ischemic stroke.
- Randomization can be performed between 2 and 15 days after stroke onset and by the research group at the patient's local/emergency hospital.
- Persisting focal neurological deficit is present at the time of randomization severe enough to warrant treatment from the physicians and the patient's and relative's perspective.
Who cannot join
- Subarachnoidal hemorrhage except where secondary to a primary intracerebral hemorrhage.
- Unlikely to be available for follow up for the next 12 months e.g. no fixed home address.
- Unable to speak Swedish and no close family member available to help with follow up forms.
- Other life threatening illness (e.g. advanced cancer) that will make 12-month survival unlikely.
- History of epileptic seizures.
- History of allergy or contraindications to fluoxetine including: Hepatic impairment (S-ASAT/ALAT > 3 upper normal limit) and renal impairment (S-Creatinine levels > 180 micromol/L).
Show all 11Show fewer
- Pregnant or breastfeeding, women of childbearing age not taking contraception. Minimum contraception is an oral contraceptive. An HCG-test is to be made prior randomization and after the end of trial medication.
- Previous drug overdose or attempted suicide.
- Already enrolled into a CTIMP.
- Current or recent (within the last month) depression requiring treatment with an SSRI antidepressant.
- Current use of medications which have serious interactions with fluoxetine Use of any mono-amino-oxidase inhibitor (MAOI) during the last 5 weeks. Co-administration of Fluoxetine and a mono-amino-oxidase inhibitor (MAOI) may result in life threatening interactions. Therefore, patients on MAOI are ineligible for the EFFECTS trial. Also, any patient in need of treatment with a MAOI must stop their trial treatment for at least 5 weeks before commencing the MAOI, or to be treated as in-patients by a psychiatrist.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Establishing the Effect(s) and Safety of Fluoxetine Initiated in the Acute Phase of Stroke
The purpose of this study is to investigate whether routine administration of fluoxetine 20mg once daily in the 6 months initiated during the acute stroke improves the patient's functional outcome.
EFFECTS is an investigator lead Sweden-based, multicenter, parallel group, double blind placebo controlled trial with broad entry criteria and follow up at 6 and 12 months.
EFFECTS managed to recruit its anticipated numbers of 1,500 participants between 20th October 2014 and 28th June 2019. Data will be unblinded when the 6-months follow-up is completed, and the primary outcome is due to report on May 2020.
Read the detailed description
Stroke is a serious, life-threatening medical condition that happens when the blood supply to a part of the brain is cut off, usually due to a blood clot (ischemic) or hemorrhage. Symptoms vary according to how much of the brain is affected and where in the brain the stroke occurs but includes paralysis, muscle weakness and speech problems.
A stroke can also have an impact on the sufferers emotions and can lead to anxiety, depression and personality changes. Fluoxetine (otherwise known as Prozac) has been used for many years to treat depression. However, there is evidence to suggest that it may also have other effects of the brain and enhance brain plasticity (the reorganisation of neural pathways in the brain) in a number of different ways.
One small study, for example, has shown that, if taken soon after a stroke, fluoxetine might improve the recovery of arm strength and lead to greater restoration of movement of the limbs.
Adult participants (at least 18 years old) who have had a stroke (either ischemic or hemorrhagic) within the last 2-15 days and still have some residual problems caused by the stroke e.g. weakness, or problems with their speech (speech impairment).
Participants are randomly allocated into one of two groups. Those in group 1 are given fluoxetine capsules for 6 months. Those in group 2 are given a placebo capsules for 6 months.
The participants are contacted after one week of starting their treatment, and then again after one month, to check on their well-being and that they are still taking their allocated caplets. Each participant is asked about any side effects and how much training they have had with e.g. a physiotherapist, occupational- or speech-therapist.
The research team contacts each participant at 3 months to check whether they are still taking the capsules, ask about bad side effects, and about how they are feeling (mood). If all is well, the participant is given enough medication to cover the rest of the study period.
The participant is asked to stop the study medication after 6 months and repeat assessments that they did before they started the study at the local hospital. They are also asked to fill in questionnaires together with their next of kin or carer. These questionnaires are sent to the trial main centre. If needed, they can also be filled in with the help of a trial nurse over the telephone.
The participants are contacted again one month after they have stopped the medication to see how they have progressed.
At 12 months after recruitment, participants are asked to complete the same questionnaires again about how well they have recovered from their stroke and what problems they now have after the stroke e.g. weakness in limbs, memory problems, problems with speech, low mood. These questionnaires can again be completed on paper or by telephone. The researchers then collect data on long-term recovery through national statistics.
- Conditions
- Stroke
- Being tested
- Fluoxetine, Placebo
- Keywords
- fluoxetine, outcome, depression, plasticity
- Medical subject headings
- Stroke, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoxetineDrug
Fluoxetine 20mg once daily for 6 months.
PlaceboDrug
Matching placebo.
| Study group | Role | What they receive |
|---|---|---|
| Fluoxetine | Active comparator | One capsule Fluoxetine 20mg once daily for 6 months. Receives: Drug: Fluoxetine |
| Placebo | Placebo comparator | One matching capsule placebo once daily for 6 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional status, measured with the modified Rankin scale.
The simple modified Rankin scale questionnaire delivered by postal questionnaire, or via interview over the telephone or face to face to determine the modified Rankin scale.
Measured: 6 months
Secondary outcomes (28)
Survival
Survival will be analysed with the Cox proportional hazards model adjusting for the factors included in the minimisation algorithm
Measured: This will be determined by following patients up for 12 months.
Functional status, measured with the modified Rankin scale.
The simple modified Rankin scale questionnaire delivered by postal questionnaire, or via interview over the telephone or face to face to determine the modified Rankin scale. The study will also investigate if the benefits of Fluoxetine remains at 12 months.
Measured: 12 months
Health status measured with the Stroke Impact Scale
Health status will be measured with the Stroke Impact Scale
Measured: At 6 and 12 months
Arm, hand, leg and foot strength assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
The 8 domains in the Stroke Impact Scale will be used for secondary outcome measures 5 to 13.
Measured: At 6 and 12 months
Hand function assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Mobility assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Communication and understanding assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Memory and thinking assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Mood and emotions assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Daily activities assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Participation in work, leisure and social activities assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Overall rating of recovery assessed with the Stroke Impact Scale
The Stroke Impact Scale will provide an overall assessment of patient outcome as well as allowing us to assess the effect of treatment on specific outcomes of importance to the patients. The Stroke Impact Scale was developed with input from both patients and caregivers and includes 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, participation) from across the full impairment-participation continuum.
Measured: At 6 and 12 months
Adverse events/outcomes
We will specifically ask for adverse events at each follow-up time (1 week, 1 month, 3 months, 6 months and 12 months), see the outcome 16-24 below. The definition of the SAE is defined according to Good Clinical Practice. We will not register known side effects of fluoxetine, which are listed in the drug's Summary of Product Characteristics. We will not register known problems following stroke, such as pneumonia, deep vein thrombosis etc.
Measured: At 6 and 12 months
Depression using the Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression using the Montgomery-Åsberg Depression Rating Scale (MADRS) and patients scoring high have a diagnosis of depression confirmed based on the DSM-IV criteria.
Measured: At 6 and 12 months
Number of participants with a recurrent stroke including ischaemic and hemorrhagic strokes
Number of participants with a recurrent stroke including ischaemic and hemorrhagic strokes
Measured: At 6 and 12 months
Number of participants with an acute coronary syndromes
Number of participants with an acute coronary syndromes
Measured: At 6 and 12 months
Number of participants with an Epileptic seizures
Number of participants with an epileptic seizures
Measured: At 6 and 12 months
Number of participants with an episodes of Hyponatraemia
Number of participants with an episodes of hyponatraemia (<125 mmol/l)
Measured: At 6 and 12 months
Number of participants with an upper gastrointestinal bleeding
Number of participants with an upper gastrointestinal bleeding
Measured: At 6 and 12 months
Number of participants with other major bleeds
Number of participants with an other major bleeds includes lower GI, extracranial, intracranial but extracerebral
Measured: At 6 and 12 months
Number of participants with poorly controlled diabetes
Number of participants with an poorly controlled diabetes including hyperglycaemia (>22 mmol/l) and hypoglycaemia
Measured: At 6 and 12 months
Number of participants with falls resulting in injury
Number of participants with falls resulting in injury
Measured: At 6 and 12 months
Number of participants with new fractures
Number of participants with new fractures
Measured: At 6 and 12 months
Fatigue measured with the vitality subscale of the Health Questionnaire
Fatigue will be measured with the vitality subscale of the Health Questionnaire, equivalent to SF 36.
Measured: At 6 and 12 months
Cognition assessed with the Stroke Impact Scale
Cognition-the Stroke Impact Scale, which incorporates an assessment of memory and thinking, is used in conjunction with with the Montreal Cognitive Assessment (MoCA)
Measured: At 6 and 12 months
Health-related quality of life measured with the five-level Euroqol 5D (EQ5D-5 L)
Health-related quality of life measured with the five-level Euroqol 5D (EQ5D-5 L).
Measured: At 6 and 12 months
Cost-effectiveness and cost-utility assessed by measuring costs, survival and health related quality of life (EQ5D)
Direct and indirect costs will be estimated at 3-month, 6- month and 1 year. Effects will be measured using survival and EuroQoL 5 Dimensions (EQ5D) scale, which will be estimated into a utility score. The effectiveness measure that will be used for comparison purposes, the quality adjusted life years (QALYs), will be estimated by multiplying the relevant time parameter of the comparison with the estimated utility scores.
A societal perspective will be adapted for the analysis, and comparison of costs and effects (QALYs) will be conducted for the period of the clinical trial, as well as by adopting a lifetime perspective, where costs and QALYs will be extrapolated beyond the duration of the trial over the expected lifetime of patients. Standard statistical regressions will be used in order to calculate the expected lifetime costs and QALYs.
Measured: At 6 and 12 months
Physical activity
Physical activity will be measured using the Saltin-Grimby Physical Activity Level Scale
Measured: 1 week, 1 month, 3 months, and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2016 (estimated)
- Study start20 Oct 2014
- Primary completionJun 2020
- Study completionJun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- The Swedish Research Council, Swedish Heart Lung Foundation, Stroke-Riksförbundet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Hjärnfonden (The Swedish Brain foundation), The Swedish Medical Association
- Responsible party
- Principal investigator, Erik Lundström, MD, PhD, Karolinska Institutet
- Investigators
- Erik Lundström, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02683213
- Sponsor's protocol ID
- EFFECTS2012
- Other IDs
- 2011-006130-16
- Acronym
- EFFECTS
- Status last verified
- Sep 2020
- First submitted
- 2 Feb 2016
- Last updated
- 2 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Three trial investigator teams have collaboratively developed a core protocol for Fluoxetine after stroke. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients.
Publications
Mead G, Hackett ML, Lundstrom E, Murray V, Hankey GJ, Dennis M. The 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. Trials. 2015 Aug 20;16:369. doi: 10.1186/s13063-015-0864-1.
PubMed 26289352Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, Hackett ML. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD009286. doi: 10.1002/14651858.CD009286.pub2.
PubMed 23152272Graham C, Lewis S, Forbes J, Mead G, Hackett ML, Hankey GJ, Gommans J, Nguyen HT, Lundstrom E, Isaksson E, Nasman P, Rudberg AS, Dennis M. The 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. Trials. 2017 Dec 28;18(1):627. doi: 10.1186/s13063-017-2385-6.
PubMed 29282099Lundstrom E, Isaksson E, Wester P, Laska AC, Nasman P. Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial. Trials. 2018 Jan 8;19(1):14. doi: 10.1186/s13063-017-2367-8.
PubMed 29310679Legg LA, Rudberg AS, Hua X, Wu S, Hackett ML, Tilney R, Lindgren L, Kutlubaev MA, Hsieh CF, Barugh AJ, Hankey GJ, Lundstrom E, Dennis M, Mead GE. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD009286. doi: 10.1002/14651858.CD009286.pub4.
PubMed 34780067Lundstrom E, Isaksson E, Greilert Norin N, Nasman P, Wester P, Martensson B, Norrving B, Wallen H, Borg J, Hankey GJ, Hackett ML, Mead GE, Dennis MS, Sunnerhagen KS. Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial. Stroke. 2021 Oct;52(10):3082-3087. doi: 10.1161/STROKEAHA.121.034705. Epub 2021 Aug 31.
PubMed 34465201Mead GE, Graham C, Billot L, Nasman P, Lundstrom E, Lewis S, Hankey GJ, Hackett ML, Forbes J, Dennis M; FOCUS, AFFINITY and EFFECTS trialists. Update 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. Trials. 2020 Nov 25;21(1):971. doi: 10.1186/s13063-020-04875-1.
PubMed 33239053EFFECTS Trial Collaboration. Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020 Aug;19(8):661-669. doi: 10.1016/S1474-4422(20)30219-2.
PubMed 32702335Lundstrom E, Isaksson E, Nasman P, Wester P, Martensson B, Norrving B, Wallen H, Borg J, Dennis M, Mead G, Hankey GJ, Hackett ML, Sunnerhagen KS; EFFECTS Trial Collaboration. Update on the EFFECTS study of fluoxetine for stroke recovery: a randomised controlled trial in Sweden. Trials. 2020 Feb 28;21(1):233. doi: 10.1186/s13063-020-4124-7.
PubMed 32111264Isaksson E, Wester P, Laska AC, Nasman P, Lundstrom E. Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel. Trials. 2019 Oct 30;20(1):618. doi: 10.1186/s13063-019-3737-1.
PubMed 31666093
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Establishing the Effect(s) and Safety of Fluoxetine Initiated in the Acute Phase of Stroke
- ClinicalTrials.gov ID
- NCT02683213
- Acronym / sponsor ID
- EFFECTS / EFFECTS2012
- Conditions
- Stroke
- Keywords
- fluoxetine, outcome, depression, plasticity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,500 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- The Swedish Research Council, Swedish Heart Lung Foundation, Stroke-Riksförbundet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Hjärnfonden (The Swedish Brain foundation), The Swedish Medical Association
- Study start
- 20 Oct 2014 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 17 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate whether routine administration of fluoxetine 20mg once daily in the 6 months initiated during the acute stroke improves the patient's functional outcome.
EFFECTS is an investigator lead Sweden-based, multicenter, parallel group, double blind placebo controlled trial with broad entry criteria and follow up at 6 and 12 months.
EFFECTS managed to recruit its anticipated numbers of 1,500 participants between 20th October 2014 and 28th June 2019. Data will be unblinded when the 6-months follow-up is completed, and the primary outcome is due to report on May 2020.
Detailed description
Stroke is a serious, life-threatening medical condition that happens when the blood supply to a part of the brain is cut off, usually due to a blood clot (ischemic) or hemorrhage. Symptoms vary according to how much of the brain is affected and where in the brain the stroke occurs but includes paralysis, muscle weakness and speech problems.
A stroke can also have an impact on the sufferers emotions and can lead to anxiety, depression and personality changes. Fluoxetine (otherwise known as Prozac) has been used for many years to treat depression. However, there is evidence to suggest that it may also have other effects of the brain and enhance brain plasticity (the reorganisation of neural pathways in the brain) in a number of different ways.
One small study, for example, has shown that, if taken soon after a stroke, fluoxetine might improve the recovery of arm strength and lead to greater restoration of movement of the limbs.
Adult participants (at least 18 years old) who have had a stroke (either ischemic or hemorrhagic) within the last 2-15 days and still have some residual problems caused by the stroke e.g. weakness, or problems with their speech (speech impairment).
Participants are randomly allocated into one of two groups. Those in group 1 are given fluoxetine capsules for 6 months. Those in group 2 are given a placebo capsules for 6 months.
The participants are contacted after one week of starting their treatment, and then again after one month, to check on their well-being and that they are still taking their allocated caplets. Each participant is asked about any side effects and how much training they have had with e.g. a physiotherapist, occupational- or speech-therapist.
The research team contacts each participant at 3 months to check whether they are still taking the capsules, ask about bad side effects, and about how they are feeling (mood). If all is well, the participant is given enough medication to cover the rest of the study period.
The participant is asked to stop the study medication after 6 months and repeat assessments that they did before they started the study at the local hospital. They are also asked to fill in questionnaires together with their next of kin or carer. These questionnaires are sent to the trial main centre. If needed, they can also be filled in with the help of a trial nurse over the telephone.
The participants are contacted again one month after they have stopped the medication to see how they have progressed.
At 12 months after recruitment, participants are asked to complete the same questionnaires again about how well they have recovered from their stroke and what problems they now have after the stroke e.g. weakness in limbs, memory problems, problems with speech, low mood. These questionnaires can again be completed on paper or by telephone. The researchers then collect data on long-term recovery through national statistics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluoxetine | Active comparator | Drug: FluoxetineOne capsule Fluoxetine 20mg once daily for 6 months. |
| Placebo | Placebo comparator | Drug: PlaceboOne matching capsule placebo once daily for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Informed consent can only be obtained from a patient who according to the trial investigator is mentally capable of decision-making and who, after having received information and got answers to their questions, wants to participate in the trial.
- Brain imaging is compatible with intra cerebral hemorrhage or ischemic stroke.
- Randomization can be performed between 2 and 15 days after stroke onset and by the research group at the patient's local/emergency hospital.
- Persisting focal neurological deficit is present at the time of randomization severe enough to warrant treatment from the physicians and the patient's and relative's perspective.
Key exclusion criteria (11 listed)
- Subarachnoidal hemorrhage except where secondary to a primary intracerebral hemorrhage.
- Unlikely to be available for follow up for the next 12 months e.g. no fixed home address.
- Unable to speak Swedish and no close family member available to help with follow up forms.
- Other life threatening illness (e.g. advanced cancer) that will make 12-month survival unlikely.
- History of epileptic seizures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluoxetineFluoxetine 20mg once daily for 6 months. | Drug | Fluoxetine |
| PlaceboMatching placebo. | Drug | Placebo |
Primary outcome
Functional status, measured with the modified Rankin scale.
Time frame: 6 months
The simple modified Rankin scale questionnaire delivered by postal questionnaire, or via interview over the telephone or face to face to determine the modified Rankin scale.
28 secondary outcomes
Survival
Time frame: This will be determined by following patients up for 12 months.
Functional status, measured with the modified Rankin scale.
Time frame: 12 months
Health status measured with the Stroke Impact Scale
Time frame: At 6 and 12 months
Arm, hand, leg and foot strength assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Hand function assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Mobility assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Communication and understanding assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Memory and thinking assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Mood and emotions assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Daily activities assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Participation in work, leisure and social activities assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Overall rating of recovery assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Adverse events/outcomes
Time frame: At 6 and 12 months
Depression using the Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: At 6 and 12 months
Number of participants with a recurrent stroke including ischaemic and hemorrhagic strokes
Time frame: At 6 and 12 months
Number of participants with an acute coronary syndromes
Time frame: At 6 and 12 months
Number of participants with an Epileptic seizures
Time frame: At 6 and 12 months
Number of participants with an episodes of Hyponatraemia
Time frame: At 6 and 12 months
Number of participants with an upper gastrointestinal bleeding
Time frame: At 6 and 12 months
Number of participants with other major bleeds
Time frame: At 6 and 12 months
Number of participants with poorly controlled diabetes
Time frame: At 6 and 12 months
Number of participants with falls resulting in injury
Time frame: At 6 and 12 months
Number of participants with new fractures
Time frame: At 6 and 12 months
Fatigue measured with the vitality subscale of the Health Questionnaire
Time frame: At 6 and 12 months
Cognition assessed with the Stroke Impact Scale
Time frame: At 6 and 12 months
Health-related quality of life measured with the five-level Euroqol 5D (EQ5D-5 L)
Time frame: At 6 and 12 months
Cost-effectiveness and cost-utility assessed by measuring costs, survival and health related quality of life (EQ5D)
Time frame: At 6 and 12 months
Physical activity
Time frame: 1 week, 1 month, 3 months, and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Background: PubMed 26289352Mead G, Hackett ML, Lundstrom E, Murray V, Hankey GJ, Dennis M. The 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. Trials. 2015 Aug 20;16:369. doi: 10.1186/s13063-015-0864-1.
- Background: PubMed 23152272Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, Hackett ML. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD009286. doi: 10.1002/14651858.CD009286.pub2.
- Background: PubMed 29282099Graham C, Lewis S, Forbes J, Mead G, Hackett ML, Hankey GJ, Gommans J, Nguyen HT, Lundstrom E, Isaksson E, Nasman P, Rudberg AS, Dennis M. The 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. Trials. 2017 Dec 28;18(1):627. doi: 10.1186/s13063-017-2385-6.
- Background: PubMed 29310679Lundstrom E, Isaksson E, Wester P, Laska AC, Nasman P. Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial. Trials. 2018 Jan 8;19(1):14. doi: 10.1186/s13063-017-2367-8.
- Derived from this study: PubMed 34780067Legg LA, Rudberg AS, Hua X, Wu S, Hackett ML, Tilney R, Lindgren L, Kutlubaev MA, Hsieh CF, Barugh AJ, Hankey GJ, Lundstrom E, Dennis M, Mead GE. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD009286. doi: 10.1002/14651858.CD009286.pub4.
- Derived from this study: PubMed 34465201Lundstrom E, Isaksson E, Greilert Norin N, Nasman P, Wester P, Martensson B, Norrving B, Wallen H, Borg J, Hankey GJ, Hackett ML, Mead GE, Dennis MS, Sunnerhagen KS. Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial. Stroke. 2021 Oct;52(10):3082-3087. doi: 10.1161/STROKEAHA.121.034705. Epub 2021 Aug 31.
- Derived from this study: PubMed 33239053Mead GE, Graham C, Billot L, Nasman P, Lundstrom E, Lewis S, Hankey GJ, Hackett ML, Forbes J, Dennis M; FOCUS, AFFINITY and EFFECTS trialists. Update 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. Trials. 2020 Nov 25;21(1):971. doi: 10.1186/s13063-020-04875-1.
- Derived from this study: PubMed 32702335EFFECTS Trial Collaboration. Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020 Aug;19(8):661-669. doi: 10.1016/S1474-4422(20)30219-2.
- Derived from this study: PubMed 32111264Lundstrom E, Isaksson E, Nasman P, Wester P, Martensson B, Norrving B, Wallen H, Borg J, Dennis M, Mead G, Hankey GJ, Hackett ML, Sunnerhagen KS; EFFECTS Trial Collaboration. Update on the EFFECTS study of fluoxetine for stroke recovery: a randomised controlled trial in Sweden. Trials. 2020 Feb 28;21(1):233. doi: 10.1186/s13063-020-4124-7.
- Derived from this study: PubMed 31666093Isaksson E, Wester P, Laska AC, Nasman P, Lundstrom E. Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel. Trials. 2019 Oct 30;20(1):618. doi: 10.1186/s13063-019-3737-1.
- The EFFECTS study home page, for investigators, layman and participants in the study. Currently only available in Swedish.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Three trial investigator teams have collaboratively developed a core protocol for Fluoxetine after stroke. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik Lundström, MD, PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fluoxetine in people with Stroke, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional status, measured with the modified Rankin scale. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02683213, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020.