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

NCT03584854 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2018P000775-A
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postpartum Hemorrhage; Uterine Atony

Outcome Measures

Primary Outcomes (1)

• Uterine Tone Score

  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 Outcomes (8)

• Uterine Tone Score

  at 5 minutes following administration of the first study drug

• Number of Subjects Receiving Additional Uterotonic

  from time of delivery until surgery completion, approximately 1-2 hours

• Number of Subjects Requiring Transfusion

  within the first 24 hours after delivery of the fetus

• Number of Subjects Requiring Additional Intervention

  within the first 24 hours after delivery of the fetus

• Quantitative Blood Loss (QBL)

  from entry to exit from the OR, approximately 2 to 3 hours

Study Arms (2)

15-methyl prostaglandin F2α

ACTIVE COMPARATOR

IM Carboprost followed by Methylergonovine if needed.

Drug: 15-methyl prostaglandin F2α; Drug: Methylergonovine Maleate

Methylergonovine Maleate

ACTIVE COMPARATOR

IM Methylergonovine followed by Carboprost if needed.

Drug: 15-methyl prostaglandin F2α; Drug: Methylergonovine Maleate

Interventions

15-methyl prostaglandin F2α DRUG

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.

Also known as: Carboprost

15-methyl prostaglandin F2α; Methylergonovine Maleate

Methylergonovine Maleate DRUG

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.

Also known as: Methylergonovine

15-methyl prostaglandin F2α; Methylergonovine Maleate

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: pregnant women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Northwestern Memorial Hospital: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Cole NM, Kim JJ, Lumbreras-Marquez MI, Fields KG, Mendez-Pino L, Farber MK, Carusi DA, Toledo P, Bateman BT. Second-Line Uterotonics for Uterine Atony: A Randomized Controlled Trial. Obstet Gynecol. 2024 Dec 1;144(6):832-841. doi: 10.1097/AOG.0000000000005744. Epub 2024 Sep 26.

  PMID: 39326051 DERIVED

• 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.

  PMID: 33232518 DERIVED

MeSH Terms

Conditions

Postpartum Hemorrhage; Uterine Inertia

Interventions

Carboprost; Methylergonovine

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Dystocia

Intervention Hierarchy (Ancestors)

Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Ergonovine; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Naida Cole
• Organization: University of Chicago

nmcole@bsd.uchicago.edu

773-702-6700

Study Officials

• Naida M Cole, MD

  Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending anesthesiologist

Study Record Dates

• First Submitted: June 30, 2018
• First Posted: July 12, 2018
• Study Start: March 1, 2019
• Primary Completion: May 22, 2022
• Study Completion: June 15, 2022
• Last Updated: October 16, 2025
• Results First Posted: October 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available upon publication of the study and for 10 years thereafter.
• 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.

Locations

US (1)