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

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ClinicalTrials.gov Identifier: NCT03584854
Recruitment Status : Recruiting
First Posted : July 12, 2018
Last Update Posted : June 27, 2019
Sponsor:
Information provided by (Responsible Party):
Naida Margaret Cole, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE June 30, 2018
First Posted Date  ICMJE July 12, 2018
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE March 1, 2019
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2018)
Uterine Tone [ 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'
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03584854 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2018)
  • Uterine Tone [ 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'
  • Additional Uterotonic [ Time Frame: from time of delivery until surgery completion ]
    An additional second-line uterotonic which is given in the operating room after administration of the first study drug
  • Transfusion [ Time Frame: within the first 24 hours after delivery of the fetus ]
    The number of blood products transfused for anemia due to postpartum blood loss
  • 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
  • Quantitative Blood Loss (QBL) [ Time Frame: within the first 24 hours after delivery of the fetus ]
    The total volume of blood loss measured by a QBL scale weighing surgical drapes, towels, sponges and suction fluid
  • Hematocrit Drop [ Time Frame: from time of preoperative hematocrit value closest to delivery until time of first postoperative hematocrit ]
    Comparison of the preoperative and first postoperative hematocrit values
  • Length of Hospital Stay [ Time Frame: from day of surgery to day of hospital discharge ]
    Total duration of hospital stay (in days) after cesarean delivery
  • 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 or adverse study drug reaction
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
Official Title  ICMJE Second-Line Uterotonics in Postpartum Hemorrhage: A Randomized Clinical Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Postpartum Hemorrhage
  • Uterine Atony
Intervention  ICMJE
  • 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 Name: 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 Name: Methylergonovine
Study Arms  ICMJE
  • Active Comparator: 15-methyl prostaglandin F2α
    IM Carboprost followed by Methylergonovine if needed.
    Interventions:
    • Drug: 15-methyl prostaglandin F2α
    • Drug: Methylergonovine Maleate
  • Active Comparator: Methylergonovine Maleate
    IM Methylergonovine followed by Carboprost if needed.
    Interventions:
    • Drug: 15-methyl prostaglandin F2α
    • Drug: Methylergonovine Maleate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 30, 2018)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: pregnant women
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Naida M Cole, MD 617-732-8210 nmcole@bwh.harvard.edu
Contact: Brian T Bateman, MD, MSc 617-732-8210 bbateman@bwh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03584854
Other Study ID Numbers  ICMJE 2018P000776
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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.
Responsible Party Naida Margaret Cole, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Naida M Cole, MD Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115
PRS Account Brigham and Women's Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP