Treatment with tranexamic acid (TXA) should become the frontline response to major bleeding after childbirth, according to researchers.

Results of a global study showed that TXA can reduce death due to bleeding in women with post-partum hemorrhage, particularly when the drug is given early.

TXA reduced deaths from bleeding by 19% overall and by 31% when patients received TXA within 3 hours of giving birth.

In addition, there was no significant difference in adverse events for women who received TXA and those who received placebo.

Researchers reported these results in The Lancet.

Funds to support the drug and placebo costs in the run-in phase of the trial were provided by Pfizer. The trial was also funded by the London School of Hygiene & Tropical Medicine, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

The trial included 20,060 mothers, age 16 and older, who were treated at 193 hospitals in 21 countries.

All of the women had a clinical diagnosis of post-partum hemorrhage—defined as a blood loss of more than 500 ml within 24 hours of giving birth—after a vaginal birth or caesarean section.

The women were randomized to receive either 1 g of intravenous TXA (n=10,051) or matching placebo (n=10,009) in addition to standard care. The patients could receive a second dose of TXA or placebo if their bleeding continued after 30 minutes or stopped and restarted within 24 hours of the first dose.

The patients and their caregivers were blinded to randomization.

Results

In the final analysis, there were 10,036 women in the TXA arm and 9985 in the placebo arm.

TXA significantly reduced the risk of death from bleeding. The incidence of death from bleeding was 1.5% (n=155) among women who received TXA and 1.9% (n=191) in the placebo group. The risk ratio (RR) was 0.81 (P=0.045).

The incidence of death due to bleeding was 1.2% (n=89) among women who received TXA within 3 hours of giving birth and 1.7% (n=127) among women who received placebo within the same time period. The RR was 0.69 (P=0.008).

There was no significant difference between the treatment groups for other causes of death, and there was no significant difference in the use of hysterectomy.

Likewise, there was no significant difference between the treatment groups when it came to the composite endpoint of death from all causes or hysterectomy within 42 days of giving birth. This endpoint occurred in 5.3% (n=534) of patients in the TXA group and 5.6% (n=546) of those in the placebo group. The RR was 0.97 (P=0.65).

There was no significant difference between the treatment groups in the use of blood products. Fifty-four percent of patients in each group received blood transfusions. Among women who received transfusions, there was no significant difference in the mean number of units received.

On the other hand, there was a significant reduction in laparotomy to control bleeding for patients who received TXA (0.8%, n=82) compared to placebo (1.3%, n=127), with an RR of 0.64 (P=0.002).

There was no significant difference between the treatment groups (TXA and placebo, respectively) with regard to thromboembolic events (0.3% vs 0.3%), renal failure (1.3% vs 1.2%), cardiac failure (1.1% vs 1.2%), respiratory failure (1.1% vs 1.2%), hepatic failure (0.3% vs 0.3%), sepsis (1.8% vs 1.9%), or seizure (0.3% vs 0.4%).

And there was no significant difference between the treatment groups in quality of life measures, such as pain/discomfort, anxiety/depression, and mobility.

“We now have important evidence that the early use of tranexamic acid can save women’s lives and ensure more children grow up with a mother,” said study author Haleema Shakur, of the London School of Hygiene & Tropical Medicine in the UK.

“[TXA is] safe, affordable, and easy to administer, and we hope that doctors will use it as early as possible following the onset of severe bleeding after childbirth.”

Current World Health Organization guidelines recommend the use of TXA in post-partum hemorrhage as a treatment option if uterotonics fail to control the bleeding or if the bleeding is thought to be due to trauma.

TXA lowers risk of death from post-partum hemorrhage