NCT02683213

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,500

participants targeted

Target at P75+ for phase_3 stroke

Timeline
Completed

Started Oct 2014

Typical duration for phase_3 stroke

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 20, 2014

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

February 2, 2016

Completed
15 days until next milestone

First Posted

Study publicly available on registry

February 17, 2016

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2020

Completed
Last Updated

September 2, 2020

Status Verified

September 1, 2020

Enrollment Period

5.6 years

First QC Date

February 2, 2016

Last Update Submit

September 1, 2020

Conditions

Stroke

Keywords

fluoxetineoutcomedepressionplasticity

Outcome Measures

Primary Outcomes (1)

  • 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.

    6 months

Secondary Outcomes (28)

  • Survival

    This will be determined by following patients up for 12 months.

  • Functional status, measured with the modified Rankin scale.

    12 months

  • Health status measured with the Stroke Impact Scale

    At 6 and 12 months

  • Arm, hand, leg and foot strength assessed with the Stroke Impact Scale

    At 6 and 12 months

  • Hand function assessed with the Stroke Impact Scale

    At 6 and 12 months

  • +23 more secondary outcomes

Study Arms (2)

Fluoxetine

ACTIVE COMPARATOR

One capsule Fluoxetine 20mg once daily for 6 months.

Drug: Fluoxetine

Placebo

PLACEBO COMPARATOR

One matching capsule placebo once daily for 6 months.

Drug: Placebo

Interventions

FluoxetineDRUG

Fluoxetine 20mg once daily for 6 months.

Fluoxetine
PlaceboDRUG

Matching placebo.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Karolinska Institutet

Stockholm, 171 76, Sweden

Location

Related Publications (10)

  • 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.

    PMID: 26289352BACKGROUND

  • Mead 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.

    PMID: 23152272BACKGROUND

  • Graham 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.

    PMID: 29282099BACKGROUND

  • Lundstrom 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.

    PMID: 29310679BACKGROUND

  • Legg 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.

    PMID: 34780067DERIVED

  • Lundstrom 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.

    PMID: 34465201DERIVED

  • Mead 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.

    PMID: 33239053DERIVED

  • EFFECTS 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.

    PMID: 32702335DERIVED

  • Lundstrom 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.

    PMID: 32111264DERIVED

  • Isaksson 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.

    PMID: 31666093DERIVED

Related Links

MeSH Terms

Conditions

StrokeDepression

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

PropylaminesAminesOrganic Chemicals

Study Officials

  • Erik Lundström, MD, PhD

    Karolinska Institutet

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD, Senior Consultant in Neurology

Study Record Dates

First Submitted

February 2, 2016

First Posted

February 17, 2016

Study Start

October 20, 2014

Primary Completion

June 1, 2020

Study Completion

June 1, 2020

Last Updated

September 2, 2020

Record last verified: 2020-09

Data Sharing

IPD Sharing
Will share

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.

Locations

SE(1)