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URL: https://dx.doi.org/10.17504/protocols.io.bcw4ixgw

Authors: Rustam Al-Shahi Salman, Martin S. Dennis, Kasia Adamczuk, Karen Innes, Ruth Fraser, Jonathan Drever, Lynn Dinsmore, Carol Williams, Steff Lewis, Philip M. White, David E. Newby, Gregory Y.H. Lip, Adrian Parry-Jones, Dan Lasserson, Colin Oliver, Joanna Wardlaw, John Norrie

Summary: Primary research questionFor adults surviving spontaneous (non-traumatic) symptomatic intracranial haemorrhage with persistent/paroxysmal atrial fibrillation/flutter (AF), does starting full treatment dose oral anticoagulation (OAC) result in a beneficial net reduction of all serious vascular events compared with not starting OAC?Trial designInvestigator-led, multicentre, randomised, open, assessor-masked, parallel group, clinical trial of investigational medicinal product (CTIMP) prescribing strategies. We plan for a pilot phase, followed by a safety phase.ObjectivesPilot phase: ~30 hospital sites keep screening logs and recruit at least 60 participants >24 hours after spontaneous symptomatic intracranial haemorrhage with AF and a CHA2DS2-VASc score ≥2 to determine the acceptability and feasibility of recruiting the target sample size in a definitive trial in an acceptable timescale.Safety phase: ~60 hospital sites will recruit at least 190 participants to determine whether the risk of recurrent symptomatic intracranial haemorrhage is sufficiently low (non-inferior) to justify a definitive trial.Eligibility criteriaInclusion: Spontaneous symptomatic intracranial haemorrhage, AF and a CHA2DS2-VASc score ≥2.Exclusion: Patient age Brain magnetic resonance imaging (MRI) sub-study: MRI must be done after intracranial haemorrhage but before randomisation. Sub-study participants must not have contraindications to MRI. SettingRecruitment in secondary care (inpatient and outpatient services in stroke, general internal medicine, medicine of the elderly, cardiology, neurology and neurosurgery) with follow-up in primary and secondary care.RandomisationCentral, web-based randomisation, with 1:1 allocation of intervention: comparator, using a minimisation algorithm.InterventionStart long-term (≥1 year) full treatment dose OAC (either a non-vitamin K antagonist direct oral anticoagulant [DOAC] or vitamin K antagonist if a DOAC cannot be used), chosen by the patient’s physician before randomisation.Comparators Do not start OAC (standard clinical practice without OAC may include antiplatelet drug(s) or no antithrombotic drugs).Outcome measuresPilot phase: The proportions of eligible patients who are recruited, unsuitable, or decline to participate; the acceptability of the trial protocol to investigators and patients; and the rate of recruitment per site.Safety phase: Primary outcome: Recurrent, symptomatic, spontaneous intracranial haemorrhage. Exploratory outcomes: All symptomatic serious vascular events (i.e. major adverse cardiac or cerebrovascular events [MACCE]) including non-fatal stroke and spontaneous subdural haemorrhage, non-fatal myocardial infarction, vascular death, sudden death, or death of unknown cause. Individual symptomatic vascular events. Individual types of fatal events. Dependence according to the modified Rankin Scale.Follow upAt least one year after randomisation, using annual questionnaires to participants and their GPs, including review of any medical records and brain imaging relating to outcomes.Sample sizeWe plan to recruit at least 60 participants in a pilot phase and at least 190 participants in a safety phase (12% equivalence margin in the outcome of symptomatic intracranial haemorrhage, 1-sided p=0.025 and power 90%).

Affiliations: University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Edinburgh, University of Newcastle-upon-Tyne, University of Edinburgh, University of Liverpool, University of Manchester, University of Birmingham, The Stroke Association, University of Edinburgh, University of Edinburgh

External URL: http://www.SoSTART.ed.ac.uk

Version: 1

Publication Date: 2020

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