WOMAN trial: TXA in PPH

Question 1

What was the aim of the WOMAN trial?

Answer 1

To assess the effects of early administration of tranexamic acid on death, hysterectomy and other relevant outcomes in women with postpartum haemorrhage.

Question 2

Describe the study design of the WOMAN trial:

Answer 2

• Study type: Multicentre, randomised, double-blind, placebo-controlled trial.
• Inclusion criteria: 16 years old or greater; clinical diagnosis of PPH after vaginal or Caesarean section delivery.

Treatment groups:

• TXA grp (10,051): received 1g TXA IV in addition to usual care.
• Placebo grp (10,009): received IV placebo in addition to usual care

Method:

• If bleeding continued after 30 min or stopped and restarted with 24 hours of the first dose, a second dose of assigned treatment (TXA or placebo) could be given.
• Outcomes were measured at hospital discharge or on day 42 if still in hospital.

Question 3

What were the primary outcomes for the WOMAN trial?

Answer 3

• Composite of death from all causes

- Hysterectomy within 42 days of randomisation.

Question 4

What were the secondary outcomes for the WOMAN trial?

Answer 4

• Death due to bleeding.
• Thromboembolic events: DVT, PE, MI, Stroke
• Surgical interventions: Bakri balloon, embolisation, brace sutures, arterial ligation, hysterectomy, laparotomy after randomisation to control bleeding
• Complications: organ failure
• Adverse events

Question 5

Describe the main results and conclusions from the WOMAN trial:

Answer 5

Primary outcomes:

• Risk of death due to bleeding significantly reduced in TXA grp (1.5% vs 1.9%), RR 0.81.
• TXA given within 3 hrs of birth substantially reduced risk of death due to bleeding (1.2% vs 1.7%, RR 0.69.
• No reduction if TXA given after 3 hrs, RR 1.07.
• Death from other causes did not differ significantly between grps.

Secondary outcomes:

• Significant reduction in laparotomy to control bleeding with TXA (0.8% vs 1.3%), RR 0.64.
• Incidence of thromboembolic events did not differ significantly between grps.
• Incidence of complications did not differ significantly between grps.
• No difference in QoL.

Conclusions:

• Administration of TXA to women with PPH reduces deaths due to bleeding and laparotomy to control bleeding with no evidence of adverse effects or complications.
• The sooner TXA is given after delivery, the better the effect.

Question 6

What were the strengths of the WOMAN trial?

Answer 6

• Similar baseline characteristics.
• Double-blinded.
• Almost all pts followed-up.
• Effect of TXA on death due to bleeding is generalisable.

Question 7

What were the limitations fo the WOMAN trial?

Answer 7

• Effect of TXA on all cause mortality is not generalisable.
• > 25% deaths due to causes other than bleeding; another study would have to be much larger than this one to show a statistically significant reduction in all-cause mortality.
• Timing of hysterectomy (often early decision) means TXA may not have been administered before decision for hysterectomy or not have had time to work, hence effect on hysterectomy may not be seen.