Postpartum HemorrhagePhase 4NCT03584854
Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
A Phase 4 study testing 15-methyl prostaglandin F2α and Methylergonovine Maleate in people with Postpartum Hemorrhage and Uterine Atony, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Hemorrhage, Uterine Atony
- What is being tested?
- 15-methyl prostaglandin F2α and Methylergonovine Maleate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2019to 15 Jun 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
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.
Read the 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.
- Conditions
- Postpartum Hemorrhage, Uterine Atony
- Being tested
- 15-methyl prostaglandin F2α, Methylergonovine Maleate
- Medical subject headings
- Postpartum Hemorrhage, Uterine Inertia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
15-methyl prostaglandin F2αDrug
Also called Carboprost
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.
Methylergonovine MaleateDrug
Also called Methylergonovine
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.
| Study group | Role | What they receive |
|---|---|---|
| 15-methyl prostaglandin F2α | Active comparator | IM Carboprost followed by Methylergonovine if needed. Receives: Drug: 15-methyl prostaglandin F2α; Drug: Methylergonovine Maleate |
| Methylergonovine Maleate | Active comparator | IM Methylergonovine followed by Carboprost if needed. Receives: Drug: 15-methyl prostaglandin F2α; Drug: Methylergonovine Maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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'.
Measured: at 10 minutes following administration of the first study drug
Secondary outcomes (8)
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'
Measured: at 5 minutes following administration of the first study drug
Number of Subjects Receiving Additional Uterotonic
An additional second-line uterotonic which is given in the operating room after administration of the first study drug
Measured: from time of delivery until surgery completion, approximately 1-2 hours
Number of Subjects Requiring Transfusion
The need for RBC transfusion due to postpartum blood loss.
Measured: within the first 24 hours after delivery of the fetus
Number of Subjects Requiring Additional Intervention
The need for an additional surgical or radiologic intervention to control postpartum hemorrhage
Measured: within the first 24 hours after delivery of the fetus
Quantitative Blood Loss (QBL)
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.
Measured: from entry to exit from the OR, approximately 2 to 3 hours
Hematocrit Drop
Comparison of the preoperative and first postoperative hematocrit values
Measured: from time of preoperative hematocrit value before delivery until time of first postoperative hematocrit (within 24 hours postoperatively).
Length of Hospital Stay
Total duration of hospital stay (in days)
Measured: from day of surgery to day of hospital discharge, approximately 3 days in most cases
Number of Subjects Experiencing Severe Maternal Morbidity
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)
Measured: from time of delivery until time of hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2018
- Study start1 Mar 2019
- Primary completion22 May 2022
- Study completion15 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postpartum HemorrhageStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern Memorial Hospital
- Responsible party
- Principal investigator, Jimin Kim, MD, Brigham and Women's Hospital
- Investigators
- Naida M Cole, MD, Principal investigator, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03584854
- Sponsor's protocol ID
- 2018P000775-A
- Status last verified
- Sep 2025
- First submitted
- 30 Jun 2018
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39326051Parry 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.
PubMed 33232518
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03584854
- Acronym / sponsor ID
- 2018P000775-A
- Conditions
- Postpartum Hemorrhage, Uterine Atony
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Northwestern Memorial Hospital
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 22 May 2022 (actual)
- Study completion
- 15 Jun 2022 (actual)
- First posted
- 12 Jul 2018 (actual)
- Results
- Posted 16 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 15-methyl prostaglandin F2α | Active comparator | Drug: 15-methyl prostaglandin F2α, Drug: Methylergonovine MaleateIM Carboprost followed by Methylergonovine if needed. |
| Methylergonovine Maleate | Active comparator | Drug: 15-methyl prostaglandin F2α, Drug: Methylergonovine MaleateIM Methylergonovine followed by Carboprost if needed. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (8 listed)
- non-English speaking patients requiring an interpreter for urgent, unscheduled delivery
- any hypertensive disorder
- cardiovascular disease
- asthma
- refusal of transfused blood products
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 15-methyl prostaglandin F2αAlso: CarboprostParticipants 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. | Drug | 15-methyl prostaglandin F2α, Methylergonovine Maleate |
| Methylergonovine MaleateAlso: MethylergonovineParticipants 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. | Drug | 15-methyl prostaglandin F2α, Methylergonovine Maleate |
Primary outcome
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'.
8 secondary outcomes
Uterine Tone Score
Time frame: 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
Number of Subjects Requiring Transfusion
Time frame: 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
Quantitative Blood Loss (QBL)
Time frame: 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).
Length of Hospital Stay
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39326051Cole 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.
- Derived from this study: PubMed 33232518Parry 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naida M Cole, MD principal investigator
Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 15-methyl prostaglandin F2α and Methylergonovine Maleate in people with Postpartum Hemorrhage and Uterine Atony, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Uterine Tone Score (time frame: at 10 minutes following administration of the first study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03584854, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.