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| Name | Class |
|---|---|
| Northwestern Memorial Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 15-methyl prostaglandin F2α | Active Comparator | IM Carboprost followed by Methylergonovine if needed. |
|
| Methylergonovine Maleate | Active Comparator | IM Methylergonovine followed by Carboprost if needed. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 5 minutes following administration of the first study drug |
| Number of Subjects Receiving Additional Uterotonic |
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Inclusion Criteria:
Exclusion Criteria:
pregnant women
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| Name | Affiliation | Role |
|---|---|---|
| Naida M Cole, MD | Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39326051 | Derived | 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. | |
| 33232518 | 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. |
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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.
The data will be available upon publication of the study and for 10 years thereafter.
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.
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March 2019- April 2022
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| ID | Title | Description |
|---|---|---|
| FG000 | 15-methyl Prostaglandin F2α | IM Carboprost followed by Methylergonovine if needed. 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. 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. |
| FG001 | Methylergonovine Maleate | IM Methylergonovine followed by Carboprost if needed. 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. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 15-methyl Prostaglandin F2α | IM Carboprost followed by Methylergonovine if needed. 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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'. | In the carboprost group, 50 participants were enrolled and data for 49 participants were analyzed since the primary outcome was not measured in 1 participant. In the methylergonovine group, 50 participants were enrolled and data for 48 were analyzed since 2 participants did not have the primary outcome measured. | Posted | Mean | Standard Deviation | score on a scale | at 10 minutes following administration of the first study drug |
|
Adverse events were collected for each participant from the time of delivery until 1 month postpartum.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 15-methyl Prostaglandin F2α | IM Carboprost followed by Methylergonovine if needed. 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. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Naida Cole | University of Chicago | 773-702-6700 | nmcole@bsd.uchicago.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 4, 2018 | Dec 17, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 4, 2018 | Sep 29, 2025 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D006473 | Postpartum Hemorrhage |
| D014593 | Uterine Inertia |
| ID | Term |
|---|---|
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D002260 | Carboprost |
| D008755 | Methylergonovine |
| ID | Term |
|---|---|
| D011461 | Prostaglandins F, Synthetic |
| D011465 | Prostaglandins, Synthetic |
| D011453 | Prostaglandins |
| D015777 | Eicosanoids |
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|
|
| 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. |
|
|
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 | 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 | 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) | 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 | 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 | 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 | 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 |
| BG001 | Methylergonovine Maleate | IM Methylergonovine followed by Carboprost if needed. 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. 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Methylergonovine Maleate | IM Methylergonovine followed by Carboprost if needed. 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. 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. |
|
|
| Secondary | 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' | 50 participants were enrolled in the 15-methyl prostaglandin F2alpha group, and this secondary outcome was measured in all participants. 50 participants were enrolled in the methylergonovine group, but 1 did not have this secondary outcome (uterine tone score 5 minutes after administration of the first study drug) measured, therefore 49 were analyzed. | Posted | Mean | Standard Deviation | score on a scale | at 5 minutes following administration of the first study drug |
|
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | from time of delivery until surgery completion, approximately 1-2 hours |
|
|
|
| Secondary | Number of Subjects Requiring Transfusion | The need for RBC transfusion due to postpartum blood loss. | Posted | Count of Participants | Participants | within the first 24 hours after delivery of the fetus |
|
|
|
| Secondary | Number of Subjects Requiring Additional Intervention | The need for an additional surgical or radiologic intervention to control postpartum hemorrhage | Posted | Count of Participants | Participants | within the first 24 hours after delivery of the fetus |
|
|
|
| Secondary | 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. | Posted | Geometric Mean | 95% Confidence Interval | milliliters (mL) | from entry to exit from the OR, approximately 2 to 3 hours |
|
|
|
| Secondary | Hematocrit Drop | Comparison of the preoperative and first postoperative hematocrit values | Posted | Mean | Standard Deviation | percentage of initial Hct | from time of preoperative hematocrit value before delivery until time of first postoperative hematocrit (within 24 hours postoperatively). |
|
|
|
| Secondary | Length of Hospital Stay | Total duration of hospital stay (in days) | Posted | Geometric Mean | 95% Confidence Interval | days | from day of surgery to day of hospital discharge, approximately 3 days in most cases |
|
|
|
| Secondary | 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) | Posted | Count of Participants | Participants | from time of delivery until time of hospital discharge |
|
|
|
| 0 |
| 50 |
| 0 |
| 50 |
| 14 |
| 50 |
| EG001 | Methylergonovine Maleate | IM Methylergonovine followed by Carboprost if needed. 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. 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. | 0 | 50 | 0 | 50 | 13 | 50 |
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| D011644 | Puerperal Disorders |
| D014592 | Uterine Hemorrhage |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004420 | Dystocia |
| D005231 |
| Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
| D004874 | Ergonovine |
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |