Effect of Tranexamic acid for acute spontaneous intracerebral haemorrhage: A systematic review and individual patient data meta-analysis

Background Spontaneous intracerebral haemorrhage (ICH) has high rates of death and disability, and no proven haemostatic treatment. Tranexamic acid might limit haematoma expansion and improve outcomes. We conducted the first individual patient data meta-analysis to evaluate the effect of tranexamic acid on functional outcomes in spontaneous ICH.

This systematic review and individual patient data meta-analysis included randomised controlled trials comparing intravenous tranexamic acid to placebo in adults with spontaneous ICH treated within 12 hours of onset. MEDLINE, EMBASE, CENTRAL, Web of Science, and WHO ICTRP were searched to November 2024. The primary outcome was functional status at 90 days after randomisation, measured by the modified Rankin Scale. Adverse events (seizures, thromboembolic events) were also summarised. Analyses used generalised linear mixed models with random intercepts for trial. Risk of bias was assessed using the Cochrane RoB 2 tool. The study was registered with PROSPERO (CRD42022345775).

We identified 1,131 records; nine trials (3,194 participants) were eligible for inclusion and five trials (2860 participants; 90% of those available) provided individual patient data for the primary analysis. Risk of bias was low across all included trials. At 90 days, 757/1423 (53.2%) patients assigned to tranexamic acid had a worse functional outcome compared with 759/1415 (53.6%) assigned to placebo, the difference was not statistically significant (adjusted common odds ratio 0.93 (95% CI 0.81 to 1.07; p = 0.30). Serious adverse events were similar between the groups, with no significant differences observed. There was no evidence of between-trial heterogeneity based on model fit (likelihood ratio test).

Completed clinical trials provide no evidence that tranexamic acid improves functional outcome after spontaneous ICH. However, given the reduction in hematoma expansion and early mortality it remains to be seen if this translates to improved functional outcome in larger ongoing clinical trials. Even a small beneficial effect could have potential for global impact given the burden of ICH. Funding No funding source. Competing Interest Statement I have attached the conflict of interest declaration for each author Clinical Protocols https://www.crd.york.ac.uk/PROSPERO/view/54978 Funding Statement No funding sourced for this work Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All individual trials has the appropriate ethical guidelines obtained. This meta-analysis did not require ethics or IRB approvals. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Individual participant data and the data dictionary will not be made available. Requests should be sent to nikola.sprigg{at}nottingham.ac.uk.