Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
Primary Purpose
Postpartum Hemorrhage, Uterine Atony
Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
15-methyl prostaglandin F2α
Methylergonovine Maleate
Sponsored by
About this trial
This is an interventional treatment trial for Postpartum Hemorrhage
Eligibility Criteria
Inclusion Criteria:
- pregnant with a fetus >/=24 weeks gestational age
- non-emergent cesarean delivery
- postpartum hemorrhage deemed the result of uterine atony
Exclusion Criteria:
- non-English speaking patients requiring an interpreter
- 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
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
15-methyl prostaglandin F2α
Methylergonovine Maleate
Arm Description
IM Carboprost followed by Methylergonovine if needed.
IM Methylergonovine followed by Carboprost if needed.
Outcomes
Primary Outcome Measures
Uterine Tone
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'
Secondary Outcome Measures
Uterine Tone
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'
Additional Uterotonic
An additional second-line uterotonic which is given in the operating room after administration of the first study drug
Transfusion
The number of blood products transfused for anemia due to postpartum blood loss
Additional Intervention
The need for an additional surgical or radiologic intervention to control postpartum hemorrhage
Quantitative Blood Loss (QBL)
The total volume of blood loss measured by a QBL scale weighing surgical drapes, towels, sponges and suction fluid
Hematocrit Drop
Comparison of the preoperative and first postoperative hematocrit values
Length of Hospital Stay
Total duration of hospital stay (in days) after cesarean delivery
Maternal Morbidity
Any unplanned adverse reaction or event with clinical consequences e.g. cardiovascular event, intubation, ICU admission, hypovolemic shock or adverse study drug reaction
Full Information
NCT ID
NCT03584854
First Posted
June 30, 2018
Last Updated
May 23, 2022
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03584854
Brief Title
Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
Official Title
Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2019 (Actual)
Primary Completion Date
May 22, 2022 (Actual)
Study Completion Date
July 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postpartum Hemorrhage, Uterine Atony
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
15-methyl prostaglandin F2α
Arm Type
Active Comparator
Arm Description
IM Carboprost followed by Methylergonovine if needed.
Arm Title
Methylergonovine Maleate
Arm Type
Active Comparator
Arm Description
IM Methylergonovine followed by Carboprost if needed.
Intervention Type
Drug
Intervention Name(s)
15-methyl prostaglandin F2α
Other Intervention Name(s)
Carboprost
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Methylergonovine Maleate
Other Intervention Name(s)
Methylergonovine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Uterine Tone
Description
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'
Time Frame
at 10 minutes following administration of the first study drug
Secondary Outcome Measure Information:
Title
Uterine Tone
Description
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'
Time Frame
at 5 minutes following administration of the first study drug
Title
Additional Uterotonic
Description
An additional second-line uterotonic which is given in the operating room after administration of the first study drug
Time Frame
from time of delivery until surgery completion
Title
Transfusion
Description
The number of blood products transfused for anemia due to postpartum blood loss
Time Frame
within the first 24 hours after delivery of the fetus
Title
Additional Intervention
Description
The need for an additional surgical or radiologic intervention to control postpartum hemorrhage
Time Frame
within the first 24 hours after delivery of the fetus
Title
Quantitative Blood Loss (QBL)
Description
The total volume of blood loss measured by a QBL scale weighing surgical drapes, towels, sponges and suction fluid
Time Frame
within the first 24 hours after delivery of the fetus
Title
Hematocrit Drop
Description
Comparison of the preoperative and first postoperative hematocrit values
Time Frame
from time of preoperative hematocrit value closest to delivery until time of first postoperative hematocrit
Title
Length of Hospital Stay
Description
Total duration of hospital stay (in days) after cesarean delivery
Time Frame
from day of surgery to day of hospital discharge
Title
Maternal Morbidity
Description
Any unplanned adverse reaction or event with clinical consequences e.g. cardiovascular event, intubation, ICU admission, hypovolemic shock or adverse study drug reaction
Time Frame
from time of delivery until time of hospital discharge
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
pregnant women
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
pregnant with a fetus >/=24 weeks gestational age
non-emergent cesarean delivery
postpartum hemorrhage deemed the result of uterine atony
Exclusion Criteria:
non-English speaking patients requiring an interpreter
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naida M Cole, MD
Organizational Affiliation
Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
33232518
Citation
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.
Results Reference
derived
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Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
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