Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial

September 29, 2025 updated by: Jimin Kim, MD, Brigham and Women's Hospital
The aim of this study is to evaluate in a randomized fashion the comparative efficacy of two second-line medications, methylergonovine and carboprost for treating atonic postpartum hemorrhage (PPH). The investigators hypothesize that administration of methylergonovine will produce superior uterine tone to carboprost in atonic PPH.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary postpartum hemorrhage (PPH) is defined by the American College of Obstetricians and Gynecologists as a cumulative blood loss of >1000 mL within 24 hours of the birth process. PPH remains a leading source of maternal morbidity and mortality worldwide with uterine atony identified as the underlying cause in up to 80% of cases. Between 1994 and 2006, the rate of PPH increased by 26% in the United States, raising further concern for this problem.

Treatment of PPH typically begins with administration of exogenous oxytocin, a hormone responsible for uterine contraction. When postpartum bleeding persists despite oxytocin administration, a multidisciplinary approach combining mechanical, pharmacologic, and surgical measures is indicated. Approximately 3-25% of PPH cases require a second-line uterotonic agent in addition to oxytocin, with the two most commonly administered second-line agents in the U.S.A. being methylergonovine maleate (methylergonovine) and 15-methyl prostaglandin F2α (carboprost). The comparative efficacy of these two drugs is unknown and the most recent American College of Obstetricians and Gynecologists Practice Bulletin makes no recommendation on which second-line uterotonic agents to administer preferentially in the absence of contraindications.

This study will evaluate in a randomized fashion the comparative efficacy of methylergonovine and carboprost for treating atonic PPH. Patients undergoing non-emergent cesarean section (C/S) with uterine atony and no contraindications to either drug will be randomized to receive one of the two equivalent agents in a blinded fashion after oxytocin. After ten minutes, their uterine tone will be assessed by the obstetrician and reported on a 0-10 point scale.

A power calculation was performed to detect a mean difference in uterine tone between groups of 1 point on a 0-10 point scale with 80% power and significance level of 0.05. The investigators estimate 37 patients will be required in each arm. Allowing for a 20% rate of withdrawals or missing information, a total of 100 patients will be enrolled in this study.

Investigators will adhere to the FDA Expedited Safety Requirements in reporting any adverse event that is serious, unexpected, and associated with the use of the study drugs. Any such adverse event will be reported to the study site Institutional Review Board (IRB) and serious events will prompt the study to be halted until further discussion with the IRB.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • non-emergent cesarean delivery
  • ASA I-III
  • postpartum hemorrhage deemed the result of uterine atony (uterine atony at the time of delivery, despite the administration of oxytocin)

Exclusion Criteria:

  • non-English speaking patients requiring an interpreter for urgent, unscheduled delivery
  • any hypertensive disorder
  • cardiovascular disease
  • asthma
  • refusal of transfused blood products
  • coagulopathy or abnormal coagulation lab values
  • hypersensitivity to methylergonovine maleate or 15-methyl prostaglandin
  • known or suspected delayed postpartum hemorrhage after leaving the operating room

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 15-methyl prostaglandin F2α
IM Carboprost followed by Methylergonovine if needed.
Drug: 15-methyl prostaglandin F2α
Participants will receive standard intraoperative care including an infusion of oxytocin immediately postpartum. If a second-line uterotonic is requested, patients randomized to the "carboprost" study group will receive an intramuscular dose of 0.25mg (1mL) carboprost. If another second-line uterotonic is requested, the patients will receive 0.2mg (1mL) intramuscular methylergonovine.
Other Names:
  • Carboprost
Drug: Methylergonovine Maleate
Participants will receive standard intraoperative care including an infusion of oxytocin immediately postpartum. If a second-line uterotonic is requested, patients randomized to the "methergine" study group will receive an intramuscular dose of 0.2mg (1mL) methylergonovine. If another second-line uterotonic is requested, the patients will receive 0.25mg (1mL) intramuscular carboprost.
Other Names:
  • Methylergonovine
Active Comparator: Methylergonovine Maleate
IM Methylergonovine followed by Carboprost if needed.
Drug: 15-methyl prostaglandin F2α
Participants will receive standard intraoperative care including an infusion of oxytocin immediately postpartum. If a second-line uterotonic is requested, patients randomized to the "carboprost" study group will receive an intramuscular dose of 0.25mg (1mL) carboprost. If another second-line uterotonic is requested, the patients will receive 0.2mg (1mL) intramuscular methylergonovine.
Other Names:
  • Carboprost
Drug: Methylergonovine Maleate
Participants will receive standard intraoperative care including an infusion of oxytocin immediately postpartum. If a second-line uterotonic is requested, patients randomized to the "methergine" study group will receive an intramuscular dose of 0.2mg (1mL) methylergonovine. If another second-line uterotonic is requested, the patients will receive 0.25mg (1mL) intramuscular carboprost.
Other Names:
  • Methylergonovine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Uterine Tone Score
Time Frame: at 10 minutes following administration of the first study drug
Uterine contractile tone will be measured on a 0-10 score as assessed by the obstetrician; 0 is 'no tone', 10 is 'perfect tone' or 'excellent tone'.
at 10 minutes following administration of the first study drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Uterine Tone Score
Time Frame: at 5 minutes following administration of the first study drug
Uterine contractile tone will be measured on a 0-10 score as assessed by the obstetrician; 0 is 'no tone', 10 is 'perfect tone' or 'excellent tone'
at 5 minutes following administration of the first study drug
Number of Subjects Receiving Additional Uterotonic
Time Frame: from time of delivery until surgery completion, approximately 1-2 hours
An additional second-line uterotonic which is given in the operating room after administration of the first study drug
from time of delivery until surgery completion, approximately 1-2 hours
Number of Subjects Requiring Transfusion
Time Frame: within the first 24 hours after delivery of the fetus
The need for RBC transfusion due to postpartum blood loss.
within the first 24 hours after delivery of the fetus
Number of Subjects Requiring Additional Intervention
Time Frame: within the first 24 hours after delivery of the fetus
The need for an additional surgical or radiologic intervention to control postpartum hemorrhage
within the first 24 hours after delivery of the fetus
Quantitative Blood Loss (QBL)
Time Frame: from entry to exit from the OR, approximately 2 to 3 hours
The total volume of blood loss (in mL), calculated as a conversion from the measured blood loss in weight into its equivalent volume. Weight of blood loss is measured on a QBL scale that weighs surgical drapes, towels, sponges and suction fluid.
from entry to exit from the OR, approximately 2 to 3 hours
Hematocrit Drop
Time Frame: from time of preoperative hematocrit value before delivery until time of first postoperative hematocrit (within 24 hours postoperatively).
Comparison of the preoperative and first postoperative hematocrit values
from time of preoperative hematocrit value before delivery until time of first postoperative hematocrit (within 24 hours postoperatively).
Length of Hospital Stay
Time Frame: from day of surgery to day of hospital discharge, approximately 3 days in most cases
Total duration of hospital stay (in days)
from day of surgery to day of hospital discharge, approximately 3 days in most cases
Number of Subjects Experiencing Severe Maternal Morbidity
Time Frame: from time of delivery until time of hospital discharge
Any unplanned adverse reaction or event with clinical consequences (e.g., cardiovascular event, intubation, ICU admission, hypovolemic shock, transfusion reaction, or adverse study drug reaction)
from time of delivery until time of hospital discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Northwestern Memorial Hospital

Investigators

  • Principal Investigator: Naida M Cole, MD, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Actual)

May 22, 2022

Study Completion (Actual)

June 15, 2022

Study Registration Dates

First Submitted

June 30, 2018

First Submitted That Met QC Criteria

June 30, 2018

First Posted (Actual)

July 12, 2018

Study Record Updates

Last Update Posted (Estimated)

October 16, 2025

Last Update Submitted That Met QC Criteria

September 29, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P000775-A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data from this study will be de-identified and prepared in an anonymous data pack to minimize the possibility of re-identification. In the interests of the public good, ethical transparency, and economic and scientific support of future research, the data pack will be available to all appropriate requestors. The data will be shared in a secure fashion to protect the privacy of participants.

IPD Sharing Time Frame

The data will be available upon publication of the study and for 10 years thereafter.

IPD Sharing Access Criteria

Data requestors will be required to provide a detailed IRB-approved study protocol, data collection tools to be used and planned statistical analysis to the data generator. Citation of the data generator will be required if the data is used in a peer-reviewed publication.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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