AFFINITY Study Design at a Glance

This overview explains the trial design and participant journey. For the detailed methods and analysis plan, see the study protocol summary.

Study Outline AFFINITY Trial

The AFFINITY Trial was an Australasian clinical study investigating whether routine treatment with fluoxetine could improve functional recovery following a recent stroke. The study was designed as a large, randomised, double-blind, placebo-controlled trial and involved stroke units and rehabilitation centres across Australia, New Zealand and Vietnam. Participants were followed for up to one year to assess functional recovery, health outcomes and safety.

Study Purpose

The primary purpose of the AFFINITY Trial was to determine whether fluoxetine 20 mg once daily could improve functional outcomes after stroke. Treatment was started between 2 and 15 days after stroke onset and continued for 180 days. The study also examined a range of health, safety, quality-of-life and economic outcomes during the follow-up period.

Trial Design

AFFINITY was an investigator-driven, prospective, multi-centre Phase IIIb randomised controlled trial. The study used parallel treatment groups, with participants randomly assigned to receive either fluoxetine or a matching placebo. The double-blind design was intended to minimise the influence of participant and investigator expectations on the assessment of outcomes.

Participants

The study was designed for adults who had recently experienced an ischaemic or haemorrhagic stroke and continued to have measurable neurological impairment. Participants had to meet the trial’s eligibility requirements and be suitable for treatment and long-term follow-up. Key eligibility requirements included:

  • Age 18 years or older
  • Clinical diagnosis of stroke 2–15 days before randomisation
  • Brain imaging consistent with ischaemic or haemorrhagic stroke
  • Persistent measurable focal neurological deficits
  • Functional impairment meeting the study’s modified Rankin Scale requirements
  • Ability to participate in follow-up for the duration of the study

Treatment Groups

Eligible participants were randomly assigned to one of two treatment groups. Each participant received their assigned treatment once daily for 180 days, with the fluoxetine and placebo capsules designed to maintain the double-blind nature of the study. The two treatment groups were:

  • Fluoxetine: 20 mg once daily for 180 days
  • Placebo: Matching placebo capsule once daily for 180 days

Randomisation

Randomisation was performed using a password-protected central computerised randomisation service available around the clock. A minimisation algorithm was used to help maintain balance between the two treatment groups according to important prognostic characteristics. The randomisation process considered several factors that could influence recovery following stroke:

  • Time from stroke onset
  • Presence of a motor deficit
  • Presence of aphasia
  • Predicted probability of survival free of dependency at six months

Primary Outcome

The main outcome of the AFFINITY Trial was functional status at 180 days after randomisation. Functional outcome was assessed using the simplified modified Rankin Scale questionnaire (smRSq), a measure commonly used to assess disability and dependence following stroke. The primary analysis was intended to determine whether participants receiving fluoxetine had different functional outcomes compared with those receiving placebo. The assessment at 180 days represented the principal time point for evaluating the study’s primary research question.

Secondary Outcomes

In addition to functional outcome, the trial assessed several other measures of recovery and health. These outcomes were evaluated at 180 and 365 days after randomisation and provided information about the broader effects of treatment beyond the primary functional assessment. Secondary outcomes included:

  • Survival
  • Mood and depressive symptoms
  • Cognitive function
  • Communication
  • Motor function
  • Overall health status
  • Health-related quality of life
  • Functional recovery at 365 days
  • New depression requiring antidepressant treatment
  • Fatigue
  • Serious adverse events
  • Healthcare costs
  • Cost-effectiveness

Safety Monitoring

Safety was an important component of the trial, with serious adverse events monitored throughout the follow-up period. The study recorded a range of medical events that could occur during recovery after stroke or potentially be associated with treatment. Safety outcomes included:

  • New ischaemic or haemorrhagic stroke
  • Acute coronary syndrome
  • Major bleeding
  • Falls
  • New fractures
  • Epileptic seizures
  • Symptomatic hypoglycaemia
  • Symptomatic hyperglycaemia
  • New hyponatraemia
  • Attempted suicide or self-harm
  • Death

Follow-Up Schedule

Participants were followed for 365 days after randomisation, allowing investigators to examine both shorter-term and longer-term outcomes. Assessments were scheduled at several points during the study to monitor recovery, health status and safety. The planned follow-up points were:

  • 28 days
  • 90 days
  • 180 days
  • 365 days

Sample Size

The AFFINITY Trial planned to enrol 1,600 participants, with 800 participants allocated to each treatment group. The sample size was calculated to provide sufficient statistical power to detect a clinically relevant difference in functional outcome between fluoxetine and placebo. The study was designed with 90% power to detect an absolute increase in the proportion of participants achieving an mRS score of 0–2 at six months from 50% to 57.5%.

Study Timeline

The AFFINITY Trial recruited participants between January 2013 and June 2019. During this period, participating centres recruited eligible patients, administered the assigned study treatment and completed scheduled follow-up assessments. The study protocol was documented in Version 4, dated 18 November 2015, and provided the framework for investigating the potential effects of routine fluoxetine treatment following recent stroke.

Trial Coordination

The AFFINITY Trial was coordinated by the AFFINITY Trial Coordinating Centre within the Stroke Research Group at the Harry Perkins Institute of Medical Research and Sir Charles Gairdner Hospital in Western Australia. The coordinating centre supported the participating sites and managed the central aspects of the study, including trial coordination and long-term follow-up. The multi-centre design enabled the investigation to be conducted across stroke services and rehabilitation settings in Australia, New Zealand and Vietnam.

The protocol planned for 1,600 participants; the completed study recruited 1,280 participants in Australia, New Zealand and Vietnam. See the published trial report and official trial register. Return to the trial overview and results or read about the investigators and coordination.

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