Feb 25, 2020
Start or STop Anticoagulants Randomised Trial (SoSTART) after spontaneous intracranial haemorrhage
- Rustam Al-Shahi Salman1,
- Martin S. Dennis1,
- Kasia Adamczuk1,
- Karen Innes1,
- Ruth Fraser1,
- Jonathan Drever1,
- Lynn Dinsmore1,
- Carol Williams1,
- Steff Lewis1,
- Philip M. White2,
- David E. Newby1,
- Gregory Y.H. Lip3,
- Adrian Parry-Jones4,
- Dan Lasserson5,
- Colin Oliver6,
- Joanna Wardlaw1,
- John Norrie1
- 1University of Edinburgh;
- 2University of Newcastle-upon-Tyne;
- 3University of Liverpool;
- 4University of Manchester;
- 5University of Birmingham;
- 6The Stroke Association
External link: http://www.SoSTART.ed.ac.uk
Protocol Citation: 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 2020. Start or STop Anticoagulants Randomised Trial (SoSTART) after spontaneous intracranial haemorrhage. protocols.io https://dx.doi.org/10.17504/protocols.io.bcw4ixgw
Manuscript citation:
Sponsor number AC16141, EudraCT number 2016-004121-16, REC number 17/SS/0082, ClinicalTrials.gov Identifier NCT03153150, Version number 6.0, 23 January 2020
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
This is the final version of the trial protocol that was first approved before recruitment began.
Created: February 25, 2020
Last Modified: February 25, 2020
Protocol Integer ID: 33468
Keywords: stroke, intracerebral haemorrhage, randomised controlled trial, atrial fibrillation, oral anticoagulation,
Abstract
Primary research question
For 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 design
Investigator-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.
Objectives
Pilot 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 criteria
Inclusion: Spontaneous symptomatic intracranial haemorrhage, AF and a CHA2DS2-VASc score ≥2.
Exclusion: Patient age <18 years. Symptomatic intracranial haemorrhage within the last 24 hours. Brain imaging that first diagnosed the intracranial haemorrhage is not available. Intracranial haemorrhage is exclusively due to trauma or haemorrhagic transformation of ischaemic stroke. Patient or their doctor is certain about whether to start full dose OAC. Intention to implement the allocated treatment strategy for <1 year. Patient is not registered with a general practitioner. Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception. Lactose intolerance. Patient and carer unable to understand spoken or written English. Previously randomised in SoSTART.
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.
Setting
Recruitment 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.
Randomisation
Central, web-based randomisation, with 1:1 allocation of intervention: comparator, using a minimisation algorithm.
Intervention
Start 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 measures
Pilot 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 up
At 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 size
We 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%).
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