A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial CRASH-3 TrialReport as inadecuate




A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial CRASH-3 Trial - Download this document for free, or read online. Document in PDF available to download.

Trials

, 18:330

First Online: 17 July 2017Received: 20 December 2016Accepted: 28 June 2017

Abstract

BackgroundTranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid versus placebo on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid versus placebo on intracranial bleeding and cerebral ischaemia.

MethodsThe CRASH-3 Intracranial Bleeding Mechanistic Sub-Study CRASH-3 IBMS is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage from pre- to post-randomisation scans, new intracranial haemorrhage seen on post- but not pre-randomisation scans, intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions seen on post-but not pre-randomisation scans. A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals.

DiscussionThe CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury.

Trial registrationThe CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ISRCTN15088122 19 July 2011, and ClinicalTrials.gov on 25 July 2011 NCT01402882.

KeywordsTranexamic acid Intracranial haemorrhage Cerebral ischaemia Traumatic brain injury AbbreviationsCIconfidence interval

CRASHClinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

CTcomputed tomography

ORodds ratio

RRrelative risk

SPIRITStandard Protocol Items: Recommendations for Interventional Trials

TBItraumatic brain injury

Electronic supplementary materialThe online version of this article doi:10.1186-s13063-017-2073-6 contains supplementary material, which is available to authorized users.

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Author: Abda Mahmood - Ian Roberts - Haleema Shakur

Source: https://link.springer.com/







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