Update
Background
Objectives
Primary objective
Secondary objectives
Design
Inclusion criteria
Exclusion criteria
Intervention
Data collection
Primary outcome
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Poor outcome (death or dependence), defined as a mRS score of 4 to 6, at 3 months after randomisation.
Secondary outcomes
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Safety of platelet transfusion (see Safety below)
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ICH growth, defined as the absolute difference in intraparenchymal ICH volume (mL) between brain imaging at baseline and repeat imaging after 24 ± 3 hours, assessed by automated planimetric software, checked by two independent radiologists for accuracy
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Survival at 3 months
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The full ordinal score range of mRS at 3 months
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Poor outcome defined as mRS 3–6 at 3 months
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Disability at 3 months scored using the Amsterdam Medical Centre linear disability score (ALDS)
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Presence of the ‘spot sign’ on CTA at baseline and whether this modified the effect of platelet transfusion on the primary outcome and ICH growth
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Causes of poor outcome
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Cost-effectiveness of platelet transfusion
Safety
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Complications of ICH (ICH growth, brain oedema, brain herniation, intraventricular extension, hydrocephalus)
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Thromboembolic complications (cerebral infarction, myocardial infarction, systemic embolism, pulmonary embolism)
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Transfusion reactions (non-haemolytic, anaphylactic, transfusion-related acute lung injury, post-transfusion purpura, graft-versus-host disease, transfusion-transmitted bacterial infection)
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Other (infection – urinary tract or pulmonary – and epileptic seizures)
Statistical methods specified in the protocol
Sample size calculation
Proposed analyses
Interim analyses and safety reporting
Statistical analysis plan
Overall principles
Overall level of statistical significance
Handling of missing data
Definition of populations for analysis
Intention-to-treat population
As-treated population
List of analyses
Recruitment and retention
Baseline characteristics
Protocol deviations and violations
Adherence to allocated treatment
Primary outcome
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▪ Type of antiplatelet therapy used (stratification variable: cyclooxygenase inhibitor only vs. ADP receptor inhibitor only vs. cyclooxygenase inhibitor in combination with an adenosine reuptake inhibitor vs. cyclooxygenase inhibitor in combination with ADP receptor inhibitor).
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▪ ICH severity, quantified by the ICH score [24]
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▪ Any large, chance imbalances at baseline between intervention and control groups in covariates that might have a major influence on the primary outcome.
Secondary outcomes
Safety outcomes
Subgroup analyses
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▪ Pre-ICH antiplatelet therapy used: single vs. dual therapy
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▪ ICH volume at baseline, trichotomised according to the distribution of ICH volume on the baseline diagnostic scan
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▪ country of randomisation (The Netherlands vs. Scotland vs. France)