Clinical trial NCT03584854: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Postpartum Hemorrhage
Uterine Atony
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2018-07-12
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Uterine Tone
timeFrame: at 10 minutes following administration of the first study drug
Secondary outcomes:
measure: Uterine Tone
timeFrame: at 5 minutes following administration of the first study drug
measure: Additional Uterotonic
timeFrame: from time of delivery until surgery completion
measure: Transfusion
timeFrame: within the first 24 hours after delivery of the fetus
measure: Additional Intervention
timeFrame: within the first 24 hours after delivery of the fetus
measure: Quantitative Blood Loss (QBL)
timeFrame: within the first 24 hours after delivery of the fetus
measure: Hematocrit Drop
timeFrame: from time of preoperative hematocrit value closest to delivery until time of first postoperative hematocrit
measure: Length of Hospital Stay
timeFrame: from day of surgery to day of hospital discharge
measure: Maternal Morbidity
timeFrame: from time of delivery until time of hospital discharge
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115
name: Naida M Cole, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.