Author: Jonathan McMahon, DO, MA
Edited by: Robert Allen, MD; Noah Berland, MD
Tranexamic Acid (TXA) has been in the literature a lot recently. Between the HALT-IT trial for its use in GI bleed, CRASH-2 and MATTERs for its use in trauma victims, WOMAN for TXA for postpartum hemorrhage, CRASH-3 for its use in intracranial bleeds; the list continues. TXA has been approved for use in some EMS systems, including for use by FDNY EMS rescue medics. But does it have a significant impact on mortality when administered in the prehospital setting?
Our Food and Journal Club discussed the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP) trial. The paper looked to answer this question. Here are some of the highlights of our discussion.
Study design
This study was a multicenter, double-blind, placebo-controlled, randomized clinical trial that was conducted at four U.S. trauma centers and their surrounding ground and helicopter EMS systems from May 1, 2015 to Oct 31, 2019.[1] The goal enrollment was 994 patients using an estimate of 16% mortality to detect 7% difference between the 30-day mortality in TXA and placebo treatment groups.
Patients
Inclusion and exclusion criteria.[1]
Outcomes
Primary outcome: 30-day mortality
Additional prespecified outcomes and subgroup analyses.[1]
Results
927 patients were enrolled. Twenty-four were ineligible or withdrew from the study after randomization. 903 patients were included in the final study sample. They were randomized into 447 who received TXA and 456 who received placebo. Enrollment was stopped early at 93% planned enrollment because of financial constraints and slow enrollment.
Baseline characteristics. [1]
The authors went on to perform a post hoc comparison of the time to TXA and shock severity that found TXA within 1 hour showed lower 30-day mortality (4.6% TXA vs 7.6%; 95% CI, -5.7% to -0.3%; P < 0.002). Further analysis found those with SBP ≤ 70 mm Hg who received TXA in the prehospital setting had lower 30-day mortality (18.5% vs 35.5%; 95% CI, -25.8% to -8.1%; P < 0.003).
“Mortality risk by time from injury and shock severity.” “The dotted vertical line represents a risk ratio of 1.0 (no difference between groups). The squares represent the point estimate of the risk ratio, with the horizontal solid lines representing the 95%CIs.”[1]
Pros
The study was blinded and randomized. Inclusion and exclusion criteria were simple – this is important for EMS providers in the field who often have to make quick decisions. The severity of injury and shock were varied. These data also showed similar rates of venous thromboembolism (VTE) in the study groups, although the study was not powered for this analysis.
Cons/Limitations
First, the study was underpowered. Only 93% of planned enrollment was met. Also, the study was powered to 16% mortality, and this study only saw 10% mortality in the placebo group.
Second, the authors note the ISS is low overall: TXA 13 vs placebo 11. Few patients received blood products after their injuries: TXA 17% vs placebo 35%. Therefore, there is a question as to how beneficial the TXA was for the sample. Overall, TXA may have more benefit in a more critically ill cohort of patients than in this study.
Third, one of the few analyses that showed some difference was among the 16 patients in the study with systolic blood pressures < 70 mm Hg, in which TXA showed mortality benefit at 30 days (TXA 18.5% vs placebo 35.5%). This was not a prespecified subgroup analysis and should only be used to generate hypotheses.
Fourth, 200 patients were not included as they were eligible but not enrolled in the prehospital setting. This could be a source of selection bias.
Conclusions
STAAMP found that prehospital TXA administration did not improve 30-day mortality. Unfortunately, this study was stopped early and was underpowered. The limited subgroup analyses should be used to generate hypotheses and guide further research.
Our journal club participants believed that TXA in the prehospital setting does not harm, but may not help, our trauma patients. Prior studies have shown TXA to be of relatively low risk with a high number needed to harm compared to its low number needed to treat in the proper population and when administered early (CRASH-2).[3]
Follow-up studies should include further investigation into the timing of prehospital TXA administration. Additionally, further research should explore if TXA has benefit in a sicker population (those with higher ISS or lower systolic blood pressures).
References
1.Guyette, F.X., et al. Tranexamic acid during prehospital transport in patients at risk for hemorrhage after injury: A double-blind, placebo-controlled, randomized clinical trial. JAMA Surgery. 2020. E1-E10. DOI: 10.1001/jamasurg.2020.4350
2. Imputation. Glossary of Statistical Terms – Organization for Economic Co-operation and Development. https://stats.oecd.org/glossary/detail.asp?ID=3462. Published March 13, 2002. Accessed December 31, 2020.
3. McCoy, K. Tranexamic Acid for Severe Trauma. theNNT. https://www.thennt.com/nnt/tranexamic-acid-for-severe-trauma/. Published March 11, 2011. Accessed January 12, 2021.
Jonathan McMahon
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