• Shyam Murali

Journal Club: Cal-PAT Trial

Journal club at the Mercy St. Vincent EM Residency takes place once a month, and we discuss up to four potentially practice-changing papers. The discussion includes all residents and is led by senior residents or our research director, Dr. Michael Plewa. These journal club posts are designed to provide you with a deeper dive into the paper, addressing what the investigators did, the strengths and weaknesses, and the outcomes.


Neeki M, Dong F, Toy J, et al. Tranexamic Acid in Civilian Trauma Care in the California Prehospital Antifibrinolytic Therapy Study (Cal-PAT Trial). West J Emerg Med. 2018 Nov; 19(6): 977–986.


Reviewed by: Shyam Murali, MD, PGY-2


Introduction

  • Hemorrhage due to trauma = Bad

  • TXA can possibly decrease mortality

  • CRASH-2 Trial showed reduction in 28-day mortality of up to 2.4% if TXA was given within one hour of trauma, with significant but less reduction seen in the <3hr group

  • Very few high-quality prospective studies to evaluate this; even fewer pre-hospital studies

  • Cal-PAT Trial was designed to evaluate the safety and efficacy of TXA in the civilian prehospital setting in traumatic hemorrhagic shock

What did they do (PICO)?

  • Type of Study: Multi-centered, prospective, observation cohort study with a retrospective comparison

  • Population

  1. 30 EMS agencies in San Bernardino, Riverside, and Alameda Counties in California

  2. Patients >18 y/o with signs of hemorrhagic shock due to blunt or penetrating trauma • Hemorrhagic shock = SBP <90mmHg at scene, during transport, or upon arrival to trauma center, HR >120bpm, EBL 500mL in field, bleeding not controlled by direct pressure or tourniquet; OR major amputation of any extremity above wrists or above ankle

  3. Excluded from the study: • <18y/o • >3hrs post-injury • active thromboembolic event within last 24hrs • hypersensitivity to TXA • traumatic arrest with >5min of CPR w/o ROSC • penetrating cranial injury • TBI with exposed brain matter • isolated drowning/hanging victims • documented cervical cord injury with motor deficits

  • Intervention

  1. TXA given in two doses if patient met any inclusion criteria and none of the exclusion criteria (see above) • Dose #1: 1gm in 100mL of normal saline over 10 minutes, IV or IO, ASAP after patient assessment • Dose #2 after arrival to trauma center (ONLY IF patient continued to meet inclusion/exclusion criteria): 1gm in 100mL of normal saline over 8hrs

  • Comparison

  1. Control sample patients were selected from the five years of patients prior to conclusion of data collection

  2. Equivalent number patients who did not receive TXA after trauma, matched through propensity scoring based on gender, age, Injury Severity Score (ISS), and mechanism of injury (blunt vs penetrating)

  • Outcomes

  1. Primary: Mortality at 24hrs, 48hrs, and 28 days

  2. Secondary: total blood products transfused during hospital stay, hospital and ICU length of stay, SBP prior to TXA, GCS prior to TXA, incidence of known adverse events associated with TXA administration


Results

  • Patient population > 362 patients in each group, total 724 patients > Due to propensity matching process, rates of gender, age, ISS, and blunt vs penetrating were equivalent • Blunt = 37% • Penetrating = 63%

  • Primary Outcomes > Mortality at 24hrs: TXA 1.9% vs Control 3.6% (approx. NNT 59) > Mortality at 48hrs: TXA 2.8% vs Control 4.4% (approx. NNT 63) > Mortality at 28 days: TXA 3.6% vs Control 8.3% (approx. NNT 21)

  • Secondary > Fewer blood products transfused > Equivalent adverse events

  • Out of patients requiring >10 units of blood transfusion, patient who received TXA had improved mortality at 28 days (8.5% vs 23.2%)

  • Out of patients with ISS >16, patients who received TXA had improved mortality at 28 days (6% vs 14.5%)

  • 64.9% of patients were administered only the first dose of TXA; no difference in mortality if patient was given one vs two doses of TXA


Strengths

  • Multi-centered trial

  • Pretty clinically relevant primary outcome (mortality at 1, 2, and 28 days); no information about neurologic/functional outcomes, however.

  • Replicated the TXA administration used by the CRASH-2 trial

  • Paramedics and RNs underwent standardized training sessions

  • Had a system in place to discuss situation with senior physicians, familiar with study protocol


Limitations

  • Nonrandomized controlled trial

  • Nonblinded study • Although with mortality as an objective primary outcome, this limitation is reduced

  • Not powered to determine differences in adverse effects of TXA compared to control group

  • Did not address all potential confounding factors; addressed in limitations section of article


Discussions & Conclusions

  • Use of TXA in patients with hemorrhagic shock to reduce mortality at 28 days: NNT 21

  • Using TXA in prehospital setting reduced time to first TXA dose from 2.8 hours to 33 minutes

  • Author’s Conclusions

“…this study demonstrated that TXA can be effectively and feasibly administered by civilian prehospital providers and in accordance with North American emergency medicine standards. Our findings support the use of prehospital TXA in adult civilian traumatic injury with signs of hemorrhagic shock.”
  • Our Conclusions

This study does support the early use of prehospital TXA for the treatment of traumatic hemorrhagic shock in adults; however, randomized control trials have yet to be conducted to investigate this further.

Editor’s Commentary by Dr. Alex Dzurik:

This study further supports the CRASH-2 trial that TXA should be used early and often in significant trauma (and other studies are showing benefit in majority of hemorrhagic conditions). Since earlier is better, pre-hospital implementation and usage is a very reasonable direction to improve early delivery of TXA. It’s easy to forget TXA in a busy trauma situation, but it’s cheap, easy to use, low risk, and has clearly demonstrated benefit with a NNT in low 20s.



Post peer-reviewed by: Alex Dzurik, MD; Academic Faculty, Mercy Health St. Vincent’s Emergency Medicine Residency



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