Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial : the lancet

Treatment of post-partum haemorrhage with sublingual misoprostol …r: a double-blind, randomised, non-inferiority trial : The Lancet Articles
The Lancet, Pages 210 - 216, 16 January 2010doi:10.1016/S0140-6736(09)61924-3 Treatment of post-partum haemorrhage with sublingual
misoprostol versus oxytocin in women not exposed to
oxytocin during labour: a double-blind, randomised, non-
inferiority trial
Background
Oxytocin, the standard of care for treatment of post-partum haemorrhage, is not available in all settings because
of refrigeration requirements and the need for intravenous administration. Misoprostol, an effective uterotonic
agent with several advantages for resource-poor settings, has been investigated as an alternative. This trial
established whether sublingual misoprostol was similarly efficacious to intravenous oxytocin for treatment of post-
partum haemorrhage in women not exposed to oxytocin during labour.
Methods
In this double-blind, non-inferiority trial, 9348 women not exposed to prophylactic oxytocin had blood loss
measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three
tertiary-level facilities). 978 (10%) women were diagnosed with primary post-partum haemorrhage and were
randomly assigned to receive 800 µg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490). Providers and
women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min
and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be
accepted if the upper bound of the 97!5% CI fell below the predefined non-inferiority margin of 6%. All outcomes
were assessed from the time of initial treatment. This study is registered with , number
.
Findings
All randomly assigned participants were analysed. Active bleeding was controlled within 20 min with study
treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0!94, 95% CI
0!91—0!98; crude difference 5!3%, 95% CI 2!6—8!6). Additional blood loss of 300 mL or greater after treatment
occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1!78, 95% CI 1!40—
2!26). Shivering (229 [47%] vs 82 [17%]; RR 2!80, 95% CI 2!25—3!49) and fever (217 [44%] vs 27 [6%]; 8!07, 5!52—
11!8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died.
Interpretation
In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative
for post-partum haemorrhage.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61924-3/abstract?version=printerFriendly Treatment of post-partum haemorrhage with sublingual misoprostol …n: a double-blind, randomised, non-inferiority trial : The Lancet Articles
The Lancet, Pages 217 - 223, 16 January 2010doi:10.1016/S0140-6736(09)61923-1 Treatment of post-partum haemorrhage with sublingual
misoprostol versus oxytocin in women receiving prophylactic
oxytocin: a double-blind, randomised, non-inferiority trial
Background
Oxytocin, the gold-standard treatment for post-partum haemorrhage, needs refrigeration, intravenous infusion, and
skilled providers for optimum use. Misoprostol, a potential alternative, is increasingly used ad hoc for treatment of
post-partum haemorrhage; however, evidence is insufficient to lend support to recommendations for its use. This
trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-
partum haemorrhage in women receiving prophylactic oxytocin.
Methods
In this double-blind, non-inferiority trial, 31 055 women exposed to prophylactic oxytocin had blood loss measured
after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three
tertiary-level facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were randomly
assigned to receive 800 µg misoprostol (n=407) or 40 IU intravenous oxytocin (n=402). Providers and women were
masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional
blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper
bound of the 97!5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the
time of initial treatment. This study is registered with number
Findings
All randomly assigned participants were analysed. Active bleeding was controlled within 20 min after initial
treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0!99, 95% CI 0!95
—1!04; crude difference 0!4%, 95% CI "3!9 to 4!6). Additional blood loss of 300 mL or greater after treatment
occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1!12, 95% CI 0!92—1!37).
Shivering (152 [37%] vs 59 [15%]; RR 2!54, 95% CI 1!95—3!32) and fever (88 [22%] vs 59 [15%]; 1!47, 1!09—1!99) were
significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women
died.
Interpretation
Misoprostol is clinically equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be
due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour.
Funding
The Bill & Melinda Gates Foundation.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61923-1/abstract?version=printerFriendly

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