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

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

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.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Misoprostol

• Study Type: Interventional
• Enrollment (Actual): 2827
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • El Beheira
    • Damanhour, El Beheira, Egypt
      • Primary Health Care Units
    • Kafr El Dawar, El Beheira, Egypt
      • Primary Health Care Units

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secondary prevention; 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
Active Comparator: Universal prophylaxis; Single oral prophylactic dose of 600mcg (3 tablets) misoprostol administered to all women within 1 minute of deliver of baby	Drug: Misoprostol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gynuity Health Projects
• Collaborators: University of Alexandria; Ministry of Health and Population, Egypt; El Galaa Teaching Hospital
• Investigators: Principal Investigator: Emad Darwish, MD, Alexandria University; Principal Investigator: Mohamed Cherine, MD, El Galaa Teaching Hospital; Principal Investigator: Holly Anger, MPH, Gynuity Health Projects

Publications and helpful links

General Publications

• Anger HA, Dabash R, Hassanein N, Darwish E, Ramadan MC, Nawar M, Charles D, Breebaart M, Winikoff B. A cluster-randomized, non-inferiority trial comparing use of misoprostol for universal prophylaxis vs. secondary prevention of postpartum hemorrhage among community level births in Egypt. BMC Pregnancy Childbirth. 2020 May 24;20(1):317. doi: 10.1186/s12884-020-03008-5.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: August 25, 2014
• First Submitted That Met QC Criteria: August 25, 2014
• First Posted (Estimate): August 27, 2014

Study Record Updates

• Last Update Posted (Estimate): February 15, 2016
• Last Update Submitted That Met QC Criteria: February 12, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: 3004