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The Evidence for Use ofMisoprostol in the Prevention and
Treatment of Postpartum
Hemorrhage
MCHIP MeetingDhaka, May 4, 2012
Rasha Dabash, MPH
Gynuity Health Projects
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Why Misoprostol for PPH?
Conventional uterotonics (e.g. oxytocin) are theinternational standard of care for PPH but largelyunavailable or not feasible in many settings.
Misoprostol may be easier to use, more widelyavailable, lower in cost.
Growing body ofevidence to support efficacy andsafety for prevention and treatment of PPH.
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5 Scenarios for Use of Misoprostol in
PPH Management
1. Prophylactic use for PPH prevention
2. First line treatment after prophylactic
uterotonic3. First line treatment after no prophylaxis
4. Adjunct treatment
5. Hybrid strategies: Secondary
Prevention/Early liberal treatment(new idea)
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Study Context Methodology Main Outcomes
Hoj et al
2005Guinea-Bissau
Midwives
Rural health facility
RCT (n=661)
600g miso SL
vs. placebo
severe PPH w/ miso
Walraven
et al 2005The Gambia
TBAs
homebirths
RCT (n=1229)
600g miso oral
vs. oral ergo
women experienced drop
in Hb w/ miso
Derman et
al 2006
India
Midwives/ANMs
PHCs/homebirths
RCT (n=1620)
600g miso oral
vs. placebo
Acute PPH w/ miso
Severe PPH w/ miso
use of interventions w/miso
Mobeen et
al 2010Pakistan
TBAs
homebirths
RCT (n=1116)
600g miso oral
vs. placebo
Acute PPH w/ miso
women experienced drop
in Hb w/ miso
Misoprostol for PPH prevention:Community-based RCTs
Increased incidence of shivering/fever in misoprostol arms in all studies
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Scenarios 2 & 3: Misoprostol for PPH Treatment:
Overview of Two Gynuity Non-Inferiority TrialsPurpose:
To determine if 800 mcg sublingual misoprostol is similarly
efficacious to 40 IU oxytocin delivered IV for the treatment
of primary postpartum hemorrhage (PPH)
Double-blinded, placebo-controlled, randomized clinical
trials in 5 countries (two settings):
where women given oxytocin in third stage of laborwhere women not given oxytocin in third stage of labor
Sources: Blum J, Winikoff B, Raghavan S, et al. Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin inwomen receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial. Lancet Jan 2010;
Winikoff B, Dabash R, Durocher J, et al. Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women notexposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial. Lancet Jan 2010;
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Efficacy of 800 mcg sublingual misoprostol vs. 40 IUIV oxytocin in PPH treatment
407
10,052OXYTOCIN PROPHYLAXIS
41,233# SCREENED
ENROLLED
809ENROLLED
977
MISO
402
OXY
31,039NO OXYTOCIN PROPHYLAXIS
488
MISO
490
OXY
363 (90.2%)
BLEEDINGCONTROLLED
360 (95.5%)
BLEEDINGCONTROLLED
440 (89.2%)
BLEEDINGCONTROLLED
468 (89.6%)
BLEEDINGCONTROLLED
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Side Effects
With oxytocinprophylaxis: allminimal, nodifferences between2 treatments with
exception of fever &shivering
With no oxytocinprophylaxis: allminimal, vomitingsignificantly more
common withmisoprostol, fever &shivering also morecommon withmisoprostol
MISO
OXY
Oxytocin Prophylaxis No Prophylaxis
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SCENARIO 4: MISOPROSTOL AS
ADJUNCT TREATMENTPurpose: Determine if misoprostol is an effective adjuncttreatment for primary PPH (due to uterine atony)
Four studies: Hofemyer, Zuberi, Walraven, Widmer
Summary of results:
Data show no benefit of simultaneous administration of
IV oxytocin + 600 mcg sublingual misoprostol over IV
oxytocin alone for treatment of PPH
Significantly more fever in misoprostol arm
Implication of results: No reason to combine the two drugsas there is no added benefit, but more side effects
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IMPLICATIONS
PROPHYLACTICOXYTOCIN GIVEN NO PROPHYLACTICOXYTOCIN GIVEN
Immediate Treatment of PPH
IV OXYTOCINFEASIBLE
Either Drug Oxytocin Preferred
IV OXYTOCIN NOTFEASIBLE
Misoprostol Misoprostol
Adjunct PPH Treatment
No beneficial effect ofMisoprostol
??
Last resort
All Drugs++ All Drugs++
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Unanswered questions:
What is the impact of these strategies? Do they savelives?
Program effectiveness of:
misoprostol vs. oxytocin in Uniject outside oftertiary hospitals?
misoprostol for PPH treatment at lower levelfacilities/ lower level providers?
misoprostol when used for both prevention andtreatment?
Is universal provision of misoprostol for PPH preventioncost-effective?
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Universal Prevention vs. Treatment
Bleeding controlledwithin 20 mins on site?
Intervention 1:
Treatment As Needed
800 g SL Miso
(480 pills)
Intervention 2:
Universal Prophylaxis
Additional
interventions/ referral
needed
12 60
1000 Deliveries 1000 Deliveries
No prophylaxis
12% PPH120 PPH Cases
Yes: 600 g oral Miso
(3000 pills)
6% PPH
60 PPH Cases
Prophylaxis Y/N?
PPH Rate
108
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Scenario 5: Hybrid Approach: Secondary
Prevention/Liberal Treatment 9 out of 10 women who get prophylaxis dont need it
Continuum of PP bleeding and provider practices
Hybrid model: 800 mcg sublingual misoprostoladministered before PPH (blood loss 350 mls)-orapprox 25% of women (so over treating by 2X)
Advantage: medicates fewer women, reduces sideeffects, and potentially reduces cost?
Community studies underway/planned in India and
Egypt comparing universal prophylaxis to secondaryprevention
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Thank You.