Misoprostol for Secondary Prevention of Postpartum Hemorrhage at the Community Level in India

Two Community Strategies Comparing Use of Misoprostol for Secondary Prevention to Primary Prevention for Postpartum Hemorrhage: A Randomized Cluster Non-Inferiority Study in Bijapur District, Karnataka, India

This study compares two community-level strategies: selective administration of 800 mcg sublingual misoprostol to women at 350 mL blood loss for secondary prevention of postpartum hemorrhage (PPH) with universal use of 600 mcg oral misoprostol at the time of delivery for primary prevention of PPH. The study hypothesizes that at community-level births, secondary prevention for women is non-inferior (based on clinical parameters) to universal prophylaxis provided to women for primary prevention of PPH. This cluster-design non-inferiority trial has the potential to inform service delivery programs on clinical outcomes, program feasibility, cost and acceptability of two different community models of PPH care using misoprostol.

Study Overview

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

Detailed Description

Rationale for Research: There is an absence of concrete data on the programmatic and cost-effectiveness of different service delivery models for prevention and treatment of postpartum hemorrhage with misoprostol, prompting a discussion of whether resources are best spent on misoprostol for primary prevention at lower levels (with treatment carried out at higher levels via referral) or whether immediate proactive treatment strategies should be considered. As the training and policy implications of universal prevention versus selective treatment approaches vary, simple and effective service delivery models are urgently needed to help governments and organizations decide how to best focus their limited resources. This study proposes to study the efficacy of a hybrid strategy (i.e., secondary prevention) that combines elements of prevention and treatment. Results of this study could provide a new model of care that will medicate fewer women, save costs and address the clinical conundrum of guessing at the safety of administering a prevention dose of misoprostol followed quickly by a larger treatment dose.

Study design: This randomized cluster trial will recruit women with deliveries attended by auxiliary nurse midwives (ANMs) that occur at homes or at health sub-centers. ANMs will be randomized to administer the intervention as described in the primary or secondary prevention arm.

• Study Type: Interventional
• Enrollment (Actual): 3032
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Karnataka
    • Bijapur, Karnataka, India, 586103
      • Deliveries at health sub-centers and homes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. delivering at home or sub-center with an auxilliary nurse midwife (ANM)
2. able and willing to provide informed consent
3. meeting Ministry of Health Guidelines for home or sub-center delivery

Exclusion Criteria:

1. high-risk pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Primary prevention	Drug: Misoprostol; Selective administration of 800 mcg sublingual misoprostol to women with at least 350 mL blood loss within 1 hour following delivery; Drug: Misoprostol; Universal administration of 600 mcg oral misoprostol given to all women within 5 minutes of delivery of the baby
Other: Secondary Prevention	Drug: Misoprostol; Selective administration of 800 mcg sublingual misoprostol to women with at least 350 mL blood loss within 1 hour following delivery; Drug: Misoprostol; Universal administration of 600 mcg oral misoprostol given to all women within 5 minutes of delivery of the baby

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of women with post-delivery hemoglobin ≤ 7.8 gm/dL	A 20% rate of post delivery Hb ≤7.8 gm/dL in the study arm with women receiving selective administration of 800 mcg sublingual misoprostol is non-inferior to a 13% rate of post delivery Hb ≤ 7.8 gm/dL in the study arm with women receiving universal 600 mcg oral misoprostol prophylaxis.	72 hours (plus or minus 8 hours) after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of transfer to referral facilities for PPH	Proportion of women who are transferred from the location of delivery to higher level of care because the birth attendent diagnosed or suspected PPH.	within 72 hours (plus or minus 8 hours) after delivery
Rate of PPH	Proportion of women with 500 mL-999 mL blood loss following delivery, as measured by a calibrated blood collection drape.	within 1 hour after delivery
Rate of severe PPH	Proportion of women with > 1000 mL blood loss following delivery, as measured by a calibrated blood collection drape.	within 1 hour after delivery
Rate of adverse events	Adverse events include prolonged hospitalization, permanent or serious disability, additional threat to life, or death.	Within 72 hours (plus or minus 8 hours) after delivery
Mean blood loss	Blood loss will be measured using a blood collection drape, calibrated at 50 mL intervals.	1 hour after delivery
Rate of additional interventions needed to control bleeding	Addtional interventions include administration of other uterotonics (e.g., oxytocin), IV fluids, comprehensive emergency obstetric care, blood transfusion and surgery	within 72 hours (plus or minus 8 hours) after delivery
Cost-effectiveness	The cost-effectiveness of the two interventions will be compared. The cost-effectiveness measure will utilize information collected on cost of the study drug, materials used to control bleeding, and the cost of transfer and subsequent care received by women who are in in need of higher level care.	72 hours (plus or minus 8 hours) after delivery
Proportion of women reporting known side effects of misoprostol	Recognized side-effects of misoprostol include: Shivering, fever, headache, nausea, vomiting and diarrhea. Rare side effects include: abdominal pain from uterine cramping, seizures and palpitations (only with overdosing). All women in both study arms, including those in the secondary prevention arm who do not receive the study drug, will be asked if they experienced any of these symptoms.	1 hour after delivery
Acceptability of intervention to women	A brief exit interview will be conducted with participants to assess their acceptability of the intervention, including tolerability of any side effects experienced.	72 hours (plus or minus 8 hours) after delivery

Collaborators and Investigators

• Sponsor: Gynuity Health Projects
• Collaborators: University of Illinois at Chicago; University of California, San Francisco; Jawaharlal Nehru Medical College; Sri B. M. Patil Medical College, Bijapur, Karnataka, India
• Investigators: Principal Investigator: Sheila Raghavan, MSc, Gynuity Health Projects; Principal Investigator: Stacie Gellar, PhD, University of Illinois at Chicago; Principal Investigator: Suellen Miller, PhD, CNM, University of California, San Francisco; Principal Investigator: Shivaprasad S Goudar, MD, MHPE, Jawaharlal Nehru Medical College

Publications and helpful links

General Publications

• Parry Smith WR, Papadopoulou A, Thomas E, Tobias A, Price MJ, Meher S, Alfirevic Z, Weeks AD, Hofmeyr GJ, Gulmezoglu AM, Widmer M, Oladapo OT, Vogel JP, Althabe F, Coomarasamy A, Gallos ID. Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst Rev. 2020 Nov 24;11(11):CD012754. doi: 10.1002/14651858.CD012754.pub2.

Helpful Links

• Gynuity Health Projects website

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: October 27, 2011
• First Submitted That Met QC Criteria: October 28, 2011
• First Posted (Estimate): October 31, 2011

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: June 13, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Prevention; Developing countries; Misoprostol; Postpartum hemorrhage; Nurse midwife
• 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: 2.4.16