Head injury among older adults is increasingly common, frequently resulting from low-impact falls. A substantial subset of these patients were taking oral anticoagulants (OACs) before their injury to reduce the risk of stroke or systemic thromboembolism. When a traumatic intracranial haemorrhage (tICH) occurs, clinicians typically stop OACs to reduce the chance of haematoma expansion and further intracranial bleeding. However, prolonged interruption of anticoagulation exposes patients to elevated risks of ischaemic stroke, thromboembolic events and death. There is currently no consensus on the optimal timing to recommence anticoagulation after tICH, and evidence to guide practice—especially for direct oral anticoagulants (DOACs), which are now widely used—is lacking. The RESTART tICrH trial was designed to address this clinical uncertainty by comparing two pragmatic restart time points for DOAC therapy after tICH.
RESTART tICrH is a phase III, multicentre, randomised controlled trial conducted across approximately 20 trauma networks in the UK. The trial recruits adults who suffered a tICH and who were taking an OAC prior to injury. Eligible participants are randomised to one of two prespecified timings for restarting a DOAC: either 1 week or 4 weeks after the index tICH event. The study applies an intention-to-treat framework for analysis. Data collection includes clinical events, survival, functional measures, quality of life metrics and health resource utilisation.
The trial population comprises adults with traumatic intracranial haemorrhage who had been prescribed an oral anticoagulant at the time of injury. Recruitment is planned across multiple UK trauma networks to capture a representative tICH population at risk of both bleeding and thrombotic complications. The multicentre design aims to increase generalisability and to provide robust comparative data on early versus later DOAC re-initiation in routine clinical settings.
Participants are randomised to resume a DOAC either at 1 week or at 4 weeks following the tICH. The trial protocol allocates the timing of re-initiation; choice of specific DOAC agent, dose adjustments and concurrent management are expected to follow standard clinical practice and local protocols, consistent with pragmatic trial principles. Randomisation ensures balanced allocation between the two timing strategies to allow unbiased comparison of outcomes.
The primary outcome is the proportion of participants who experience either a haemorrhagic or a thrombotic event within 12 weeks of the index tICH. Secondary outcomes include:
These outcomes are intended to capture both the safety (bleeding risk) and effectiveness (prevention of thrombotic events, survival and function) implications of the two restart strategies.
Participants are followed up at 6, 12 and 26 weeks after tICH to collect clinical events, functional outcomes, quality of life measures and resource-use data. Analyses will be conducted on an intention-to-treat basis, preserving the benefits of randomisation and reflecting the assigned timing strategy regardless of subsequent adherence or treatment changes. The 12-week window is the prespecified period for the primary composite outcome assessment.
Alongside the main trial, health economic and qualitative substudies will be conducted. The economic analyses will examine resource implications and cost-effectiveness of the two strategies, while qualitative work will explore patient, caregiver and clinician perspectives on anticoagulation timing and decision-making after tICH. These substudies are designed to enrich interpretation of clinical findings and to support implementation and guideline development.
Ethical approval for the study has been obtained from the Berkshire Research Ethics Committee (reference 24/SC/0298). Written informed consent will be obtained from all participants or their legal representatives prior to enrolment. Trial findings will be disseminated via peer-reviewed journal publications, presentations at scientific conferences, registry reporting and patient-facing summaries. The investigators intend that the results will inform clinical counselling, acute-care protocols and future guideline recommendations for anticoagulation management after tICH.
The trial is registered with identifier NCT06322953. The registration provides transparency about trial aims, design and planned outcomes and will be used alongside peer-reviewed dissemination to report trial results and conclusions.