PATCH-Trauma
PubMed • ClinicalTrials.gov
Clinical Question
In patients with major trauma and suspected trauma induced bleeding, does tranexamic acid in the pre-hospital setting have better 6-month functional outcome than placebo?
Bottom Line
Pre-hospital tranexamic 1g IV bolus followed by in-hosptial 8 hour infusion decreased early mortality but did not result in a greater proportion of patients surviving with more favourable functional outcomes at 6 months.
Major Points
Owing to the findings of CRASH-2, and CRASH-3, tranexamic acid in early severe trauma in patients at risk of trauma induced coagulopathy. This trial enrolled 1310 patients and randomized them to received either pre-hospital tranexamic acid 1g IV followed by 1g IV infusion over 8 hours in hospital (n=572) to matched placebo (n=559), seeking if that would increase survival with favourable outcome at 6 months. The investigators found no statistical difference in favourable outcomes in the survivors at 6 months, 53.7% in the tranexamic acid group vs. 53.5% for placebo. For their secondary outcomes they did find a decrease in mortality at 24 hours after injury (9.7% vs. 14.1%, risk ratio 0.69; 95% CI 0.51–0.94) and 28 Days after injury (17.3% for tranexamic acid vs. 21.8% for placebo, risk ratio 0.79; 95% CI 0.63–0.99). There was some adulteration of the control arm with open label tranexamic acid and some missing data that the authors analyzed and estimated no difference from the findings of this trial.
Guidelines
As of August 2023, no guidelines have been published that reflect the results of this trial.
Design
- Multicenter, double-blind, randomized, controlled trial
- N=1310
- Tranexamic Acid (n=572)
- Placebo (n=559)
- Setting: 15 Emergency Centres in Australia, New Zealand, and Germany
- Enrollment: 28 July 2014 to 28 September 2021
- Analysis: Intention-to-treat
- Primary outcome: survival with a favourable functional outcome at 6 months, assessed with the Glasgow Outcome Scale–Extended (GOS-E)
Population
Inclusion Criteria
- adults (≥18 years of age)
- suspected severe traumatic injuries
- treated at the scene by paramedics or physicians
- transported by road or air ambulance to participating trauma centers
- assessed as being at high risk for trauma-induced coagulopathy, using the Coagulopathy of Severe Trauma (COAST) score.[1]
- if the first dose of tranexamic acid or placebo could be administered within 3 hours after injury and before hospital admission
Exclusion Criteria
- known or suspected to be pregnant
- resided in a facility for older persons
Baseline Characteristics
Tranexamic Group displayed
- Demographics: mean age 44 years, 30.1% female
- Mechanism of injury: 98.2% blunt, 6.7% penetrating, 0.5% burn
- Vitals: median initial HR 110, initial SBP ≤ 75 mmHG 38%, 76-89 mmHg 34%, ≥ 90 mmHg 27%, initial body temperature 35.5 degC
- Initial Glasgow Coma Scale: 35% <9, 7.8% 9-12, 57% 13-15
- COAST score: 0.6% <3, 36.6% 3, 38.2% 4, 18.6% 6, 5% 6
- Time from injury to first study drug: 32.6% <1h, 45.3% 1 to <2h, 22.1% ≥2h
Interventions
- Tranexamic Acid 1g as IV bolus over 10 minutes, then 1g IV over 8 hours after arrival at hospital
- match placebo
Outcomes
Comparisons are Tranexamic Acid vs. Placebo.
Primary Outcomes
- Survival with a favorable functional outcome at 6 months
- 53.7 % vs. 53.5% (Risk Ratio 1.00; 95% CI 0.90–1.12)
Secondary Outcomes
- Mortality 24 h after injury
- 9.7% vs. 14.1% (Risk Ratio 0.69; 95% CI 0.51–0.94)
- Mortality 28 Days after injury
- 17.3% vs. 21.8% (Risk Ratio 0.79; 95% CI 0.63–0.99)
- Mortality 6 months after injury
- 19% vs. 22.9% (Risk Ratio 0.83; 95% CI 0.67–1.03)
- Cause of death within 6 months after injury (none statistically different)
- Bleeding 5.6% vs. 8.3%
- vascular occlusion 0.3% vs. 0
- multiorgan failure 1.1% vs. 1.7%
- traumatic brain injury 10.2% vs. 10.7%
- other 1.1% vs. 1.6%
Subgroup Analysis
There was no statistically significant difference in subgroups based on age, time to first dose of tranexamic acid, SBP, mechanism of injury, GCS, or injury severity score
Adverse Events
- Vascular Occlusive event (none were statistically different)
- DVT 15.2% vs. 12.5%
- PE 6.5% vs. 7%
- MI 1.2% vs. 0.6%
- Ischemic stroke 2.9% vs. 2.2%
- Other arterial event 1.5% vs. 1.6%
- any of the above 23.6% vs. 19.7%
- Sepsis
- 34.4% vs. 30.9% (Risk Ratio 1.11; 95% CI 0.95–1.30)
Criticisms
- subgroups were not powered to find difference by mechanism of injury
- there was missing data from the final analysis and there was some open-label contamination of the control group
- dosing utilized in the CRASH-2/CRASH-3 trials was utilized and thus unclear if a different dising strategy would have given a different outcome
- tranexamic acid has a half-life of ~2 hours IV, unreported in the transport time and/or time between first bolus and subsequent infusion, unclear if a delay in infusion may impact outcome
Funding
- Australian National Health and Medical Research Council (NHMRC APP1044894 and APP165275)
- Health Research Council of New Zealand (GA216F)
- New Zealand Lottery Grants Board (34033)
- German Research Funding Agency (Deutsche Forschungsgemeinschaft) (MA 2569/6-1)