Comparison of Primary and Secondary Prevention of Postpartum Hemorrhage at the Community Level in Egypt

Study Overview
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Brief Summary
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The objective of this study is to compare two community-level strategies: either selective, early administration of 800 mcg sublingual misoprostol to women for secondary prevention of postpartum hemorrhage (PPH) or universal use of 600 mcg oral misoprostol at the time of delivery for prophylaxis of PPH. The significance of this cluster randomized non-inferiority trial is its potential to inform service delivery programs on clinical outcomes, program feasibility, cost, and acceptability of two different community models of PPH care using misoprostol.1. The study hypothesizes that a service delivery model that administers misoprostol for secondary prevention is non-inferior to a model that administers misoprostol for universal prophylaxis.

Official Title
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Two Community Strategies Comparing Use of Misoprostol for Secondary Prevention to Primary Prevention for Postpartum Hemorrhage: A Randomized Cluster Non-Inferiority Study in El Beheira Governorate, Egypt

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Misoprostol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give informed consent Vaginal delivery Agrees to participate in follow-up interview Agrees to have pre- and post-hemoglobin taken Delivery at woman's home or at the primary health unit (PHU) Exclusion Criteria: Too advanced into active labor to provide consent Known allergy to misoprostol and/or other prostaglandin Pregnancy complications, such as hypertension, suspected multiple pregnancy, previous caesarean section, suspected still birth, ante-partum hemorrhage, and previous complication in the third trimester
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secondary prevention<br>Single sublingual dose of 800mcg (4 tablets) misoprostol administered to women with 350-500mL postpartum blood loss as estimated using a blood absorption mat or due to deteriorating postpartum condition of the woman as determined by provider's clinical judgment | Drug: Misoprostol<br> <br> |
| Active Comparator: Universal prophylaxis<br>Single oral prophylactic dose of 600mcg (3 tablets) misoprostol administered to all women within 1 minute of deliver of baby | Drug: Misoprostol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean drop in pre- to post-delivery hemoglobin level | Hemoglobin will be measured by primary health unit staff using a portable handheld Hemocue machine. | Pre-delivery hemoglobin will be measured during a third trimester antenatal care visit or during early labor. Post-delivery hemoglbin will be measured 2 to 4 days after delivery of the baby. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of women transferred to higher level care | The proportion of women transferred to higher level care will be assessed. Includes the condition of woman at time of transfer and arrival at transfer facility. | Following delivery to postpartum visit (2 to 4 days after delivery) | 
| Proportion of women diagnosed with PPH | PPH will be diagnosed using the standard practices of PHU staff | After delivery of the baby up to 24 hours postpartum | 
| Proportion of women receiving additional interventions for PPH | An additional intervention could include: uterotonics, manual removal of placental fragments. bimanual compression, IV fluids given to control active bleeding. | Following delivery to postpartum visit (2 to 4 days after delivery) | 
| Proportion of women who experience side effects | Women experiencing known side effects of misoprostol, including shivering/chills and pyrexia; severity, duration, and any additional care provided will be assessed | From time of delivery to 2 hours postpartum | 
| Proportion of women who find the intervention acceptable | Acceptability will be assessed in an exit interview with women - women will be asked if they are willing to take misoprostol in future deliveries and about the preferences what method they would prefer (primary or secondary prevention) in future deliveries. | Measured at postpartum visit (2 to 4 days after delivery) | 
| Proportion of women who receive intervention per protocol | To assess feasibility, we will document the proportion of women for whom the intervention arm protocol is correctly followed (including correct timing of drug administration, when necessary). | within 2 hours of delivery | 
| Proportion of women experiencing a serious adverse event | Serious adverse events include hysterectomy, blood transfusion, maternal death | Within 2 to 4 days after delivery |