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Common Drug May Reduce Head Injury Deaths

— Tranexamic acid reduced mortality in mild to moderate TBI

MedpageToday
A bottle of Tranexamic acid over a CT scan of a trauma patient with a brain hemorrhage

Tranexamic acid reduced deaths in people who experienced mild to moderate traumatic brain injury (TBI) with intracranial bleeding, the showed.

When given within 3 hours of injury, tranexamic acid reduced mortality in mild to moderate TBI (RR 0.78, 95% CI 0.64–0.95), but not in severe brain injury (RR 0.99, 95% CI 0.91–1.07), reported Ian Roberts, MB, BCh, of the London School of Hygiene and Tropical Medicine in England, and co-authors in .

"Thousands of patients die needlessly because doctors and paramedics do not give tranexamic acid or give it too late," Roberts said. "It is an inexpensive, generic drug that is heat-stable with a long shelf life. It has been proven to be life-saving in patients with extracranial injury and postpartum hemorrhage. It is widely available."

"Its main 'problem' is that it is a generic drug and so no one has a stake in promoting its use," he told ľֱ. "The people who suffer from this market flaw are the public."

Recent coverage of this research by media outlets, especially and the , "could give the impression that tranexamic acid is a treatment that has been wrongly withheld by doctors up until now. However, this is not the case," the U.K's National Health Service (NHS) . "The medicine does not have a specific license for use following traumatic brain injury, and it was not guaranteed to be of benefit. Even now the results are not wholly conclusive for all patients and will need careful consideration."

Tranexamic acid helps stop bleeding by enabling blood to clot. In the U.S., the for heavy menstrual bleeding and short-term prevention in hemophilia. A North American trial recently showed that tranexamic acid did not improve neurologic outcomes for patients with acute TBI, but did improve 28-day survival rates for some patients.

Traumatic brain injury is among the most dreaded of diagnoses, observed Andrew Cap, MD, PhD, of the U.S. Army Institute of Surgical Research in Fort Sam Houston, Texas, in an . "Every physician who has cared for patients with TBI has felt the frustration that stems from being unable to alter the fatal course of traumatic brain hemorrhage in a previously healthy person," he wrote.

"The hard truths of TBI care learned from war and everyday TBI are quite simple and obvious: control bleeding, and avoid hypotension and hypoxia, or the patient will die," he said.

CRASH-3 "represents an enormous effort in studying a difficult clinical problem," Cap continued. "Considering the results of CRASH-3 with those of (20,211 patients with trauma) and (20,060 patients with peripartum hemorrhage), more than 53,000 patients have been randomly assigned in the study of tranexamic acid and the drug's effects on patients with bleeding. The results of each study independently and together are clear: tranexamic acid reduces risk of death due to bleeding, regardless of the cause."

The multi-center CRASH-3 trial included 12,737 adults in 29 countries with TBI who had intracranial bleeding on computed tomography and impaired consciousness or worse on the Glasgow Coma Scale.

From July 2012 to January 2019, the researchers randomized 6,406 patients to receive tranexamic acid -- a loading dose of 1 g of tranexamic acid infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 hours -- and 6,331 patients to receive placebo. After the trial steering committee amended the protocol to limit recruitment to within 3 hours in 2016, the study's primary outcome became head injury-related death in hospital within 28 days of injury in patients treated within 3 hours of injury. In total, 9,202 patients were treated within 3 hours, roughly split between each group.

Among all patients randomized within 3 hours, the risk of dying within 28 days did not differ between the tranexamic acid group (18.5%) and the placebo group (19.8%; RR 0.94, 95% CI 0.86–1.02). This risk, however, was reduced with tranexamic acid in patients who had mild-to-moderate injury, but not in patients with severe injury.

Early treatment was more effective than later treatment in patients with mild and moderate head injury (P=0.005), but time to treatment seemed to have no effect in patients with severe head injury (P=0.73). Tranexamic acid did not appear to increase the risk of complications from blood clots: vascular occlusive events (RR 0.98, 95% 0.74–1.28) and seizures (RR 1.09, 95% CI 0.90–1.33) were similar in both the treatment and placebo groups. The prevalence of disability among survivors also was similar between groups.

The study had several limitations, the researchers noted. Confidence intervals were wide, despite the large trial size. In addition, patients with unilateral unreactive pupils -- some of whom had brain herniation -- were not excluded from the study; including these patients may have diluted the treatment effect.

Disclosures

This research was funded by the National Institute for Health Research Health Technology Assessment, the JP Moulton Charitable Trust, the Department of Health and Social Care, the Department for International Development, the Global Challenges Research Fund, Medical Research Council, and the Wellcome Trust.

Neither the researchers nor the editorialist declared any competing interests.

Primary Source

The Lancet

Roberts I, et al "Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial" Lancet 2019; DOI: 10.1016/S0140-6736(19)32233-0.

Secondary Source

The Lancet

Cap A "CRASH-3: a win for patients with traumatic brain injury" Lancet 2019; DOI:10.1016/S0140-6736(19)32312-8.