Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial

• Published in: BMJ open 2018-02, Vol.8 (2), p.e019930-e019930
• Main Authors: Dineen, Rob A, Pszczolkowski, Stefan, Flaherty, Katie, Law, Zhe K, Morgan, Paul S, Roberts, Ian, Werring, David J, Salman, Rustam Al-Shahi, England, Tim, Bath, Philip M, Sprigg, Nikola
• Format: Article
• Language: English
• Subjects: Acids; Antifibrinolytic agents; Antifibrinolytic Agents - administration & dosage; Binding sites; Brain - diagnostic imaging; Brain - drug effects; Brain - pathology; Cerebral Hemorrhage - diagnostic imaging; Cerebral Hemorrhage - drug therapy; Double-Blind Method; Double-blind studies; Edema; Evidence-based medicine; Gene expression; Hemorrhage; Humans; Hypotheses; International Cooperation; Logistic Models; Magnetic Resonance Imaging; Neurology; Neurotoxicity; NMR; Nuclear magnetic resonance; Radiology and Imaging; Research Design; Stroke; Thrombosis; Tranexamic Acid - administration & dosage; Traumatic brain injury; Treatment Outcome
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2017-019930

ObjectivesTo test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis) or reduced perihaematomal oedema volume, perihaematomal diffusion restriction and residual MRI-defined SICH-related tissue damage (secondary hypotheses).DesignMRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214).SettingInternational multicentre hospital-based study.ParticipantsEligible adults consented and randomised in the TICH-2 trial who were also able to undergo MRI scanning. To address the primary hypothesis, a sample size of n=280 will allow detection of a 10% relative increase in prevalence of diffusion-weighted imaging (DWI) hyperintense lesions in the TXA group with 5% significance, 80% power and 5% imaging data rejection.InterventionsTICH-2 MRI substudy participants will undergo MRI scanning using a standardised protocol at day ~5 and day ~90 after randomisation. Clinical assessments, randomisation to TXA or placebo and participant follow-up will be performed as per the TICH-2 trial protocol.ConclusionThe TICH-2 MRI substudy will test whether TXA increases the incidence of new DWI-defined ischaemic lesions or reduces perihaematomal oedema or final ICH lesion volume in the context of SICH.Ethics and disseminationThe TICH-2 trial obtained ethical approval from East Midlands - Nottingham 2 Research Ethics Committee (12/EM/0369) and an amendment to allow the TICH-2 MRI sub study was approved in April 2015 (amendment number SA02/15). All findings will be published in peer-reviewed journals. The primary outcome results will also be presented at a relevant scientific meeting.Trial registration numberISRCTN93732214; Pre-results.