DESIGN: MRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214).
SETTING: International multicentre hospital-based study.
PARTICIPANTS: Eligible 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.
INTERVENTIONS: TICH-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.
CONCLUSION: The 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 DISSEMINATION: The 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 NUMBER: ISRCTN93732214; Pre-results.
DATA SOURCES: EMBASE, MEDLINE, CENTRAL, and ISI Web of Science were systematically searched from their inception until May 31, 2019.
REVIEW METHODS: Parallel-arm randomized controlled trials were included.
RESULTS: Seventy-one trials (7539 participants: orthopedics 5450 vs nonorthopedics 1909) were included for quantitative meta-analysis. In comparison to placebo, topical TXA significantly reduced intraoperative blood loss [mean difference (MD) -36.83 mL, 95% confidence interval (CI) -54.77 to -18.88, P < 0.001], total blood loss (MD -319.55 mL, 95% CI -387.42 to -251.69, P < 0.001), and incidence of blood transfusion [odds ratio (OR) 0.30, 95% CI 0.26-0.34, P < 0.001]. Patients who received topical TXA were associated with a shorter length of hospital stay (MD -0.28 days, 95% CI -0.47 to -0.08, P = 0.006). No adverse events associated with the use of topical TXA were observed, namely mortality (OR 0.78, 95% CI 0.45-1.36, P = 0.39), pulmonary embolism (OR 0.73, 95% CI 0.27-1.93, P = 0.52), deep vein thrombosis (OR 1.07, 95% CI 0.65-1.77, P = 0.79), myocardial infarction (OR 0.79, 95% CI 0.21-2.99, P = 0.73), and stroke (OR 0.85, 95% CI 0.28-2.57, P = 0.77). Of all included studies, the risk of bias assessment was "low" for 20 studies, "unclear" for 26 studies and "high" for 25 studies.
CONCLUSIONS: In the meta-analysis of 71 trials (7539 patients), topical TXA reduced the incidence of blood transfusion without any notable adverse events associated with TXA in adults undergoing surgery.
PROSPERO: CRD 42018111762.
RESULTS: Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 ( http://www.isrctn.com ).
CONCLUSION: The guideline highlights select pre-hospital criteria's and the methods for drug administration. The authors recognise that some variants may be present amongst certain institutions necessitating minor adaptations, nevertheless the core principles of advocating tranexamic acid early in the course of pre-hospital trauma should be adhered to.