dabash_evidence for use of misoprostol for prevention and treatment of pph

8/2/2019 Dabash_Evidence for Use of Misoprostol for Prevention and Treatment of PPH

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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


2/13

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;


6/13

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?


11/13

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


12/13

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


13/13

Thank You.

dabash_evidence for use of misoprostol for prevention and treatment of pph

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