Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Citation:
Shakur H, Roberts I, Fawole B, Chaudhri R, El-Sheikh M, desina Akintan, QURESHI ZAHIDA, Kidanto H, Vwalika B, Abdulkadir A, Etuk S, Noor S, Asonganyi E, Alfirevic Z, Beaumont D, Ronsmans C, Arulkumaran S. "Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial." Lancet. 2017.

Abstract:

Summary
Background
Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of
tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration
of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.
Methods
In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a
clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries.
We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual
care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of
tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box
containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those
assessing outcomes were masked to allocation. We originally planned to enrol 15
000 women with a composite primary
endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became
apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although
tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore
increased the sample size from 15
000 to 20
000 women in order to estimate the effect of tranexamic acid on the risk of
death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with
ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.
Findings
Between March, 2010, and April, 2016, 20
060
women were enrolled and randomly assigned to receive
tranexamic acid (n=10
051) or placebo (n=10
009), of whom 10
036 and 9985, respectively, were included in the analysis.
Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10
036 patients
vs
191
[1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given
treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group
vs
127 [1·7%] in the placebo group,
RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy
was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group
vs
351 [3·5%] in the placebo
group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy
was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group
vs
546 [5·5%]
in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did
not differ significantly in the tranexamic acid versus placebo group.
Interpretation
Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no
adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as
possible after bleeding onset.
Funding
London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and
Bill & Melinda Gates Foundation.

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