Background: Tranexamic acid (TXA) improves survival in severely injured adults. However, the effectiveness of TXA on overall functional outcome is unknown. We hypothesized that TXA improves overall functional outcome compared to placebo in severely injured adults.
Methods: This was an exploratory analysis of the CRASH-2 study. We included injured adults randomized 3 hours or less from the time of injury. The primary outcome measure was functional status at hospital discharge, or on day 28 if the subject was still in the hospital. Functional status was measured with the Modified Oxford Handicap Scale, a 6-category ordinal functional outcome scale. We conducted three separate analyses using three different outcome measures to evaluate the effectiveness of TXA versus placebo on functional outcomes including: 1) the mean utility-weighted Modified Oxford Handicap Scale score (overall functional outcome), 2) the area under the curve (based on functional outcome and rate of recovery), and 3) a sliding dichotomy analysis (favorable versus unfavorable functional outcome) stratified by baseline mortality risk (stratified analysis).
Results: There were 13,432 patients (6,679 randomized to placebo and 6,753 randomized to TXA) included in the study cohort. The mean utility-weighted Modified Oxford Scale score was 0.66 for patients randomized to TXA compared to a mean of 0.64 for patients randomized to placebo (mean difference 0.02 [95% confidence interval [CI] 0.01 to 0.03]). The area under the curve analysis demonstrated patients randomized to TXA had a higher 28-day mean utility-weighted Modified Oxford Scale score compared to placebo (mean score of 0.55 versus 0.53; mean difference 0.02 [95% CI 0.01 to 0.03]). The sliding dichotomy analysis demonstrated the overall proportion of patients with favorable functional outcomes was higher in the TXA group (5,360/6,753, 79.4%; 95% CI 78.4 to 80.3%) compared to the placebo group (5,174/6,679, 77.5%; 95% CI 76.5 to 78.5%); difference of 1.9% (95%CI 0.5-3.3%); number needed to treat=52.
Conclusion: Across three exploratory analyses, severely injured adult patients randomized within 3 hours from the time of injury, demonstrated better functional outcomes with TXA compared to placebo. Future trauma trials that evaluate TXA use should also consider functional status as an important outcome.