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

Postpartum Hemorrhage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03584854
• Other study ID #: 2018P000776
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 1, 2019
• Est. completion date: July 1, 2022

Study information

• Verified date: May 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). The investigators hypothesize that administration of methylergonovine will produce superior uterine tone to carboprost in atonic PPH.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: July 1, 2022
• Est. primary completion date: May 22, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage
• Uterine Atony
• Uterine Inertia

Intervention

Drug:
• 15-methyl prostaglandin F2a
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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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'	at 10 minutes following administration of the first study drug
Secondary	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'	at 5 minutes following administration of the first study drug
Secondary	Additional Uterotonic	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
Secondary	Transfusion	The number of blood products transfused for anemia due to postpartum blood loss	within the first 24 hours after delivery of the fetus
Secondary	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
Secondary	Quantitative Blood Loss (QBL)	The total volume of blood loss measured by a QBL scale weighing surgical drapes, towels, sponges and suction fluid	within the first 24 hours after delivery of the fetus
Secondary	Hematocrit Drop	Comparison of the preoperative and first postoperative hematocrit values	from time of preoperative hematocrit value closest to delivery until time of first postoperative hematocrit
Secondary	Length of Hospital Stay	Total duration of hospital stay (in days) after cesarean delivery	from day of surgery to day of hospital discharge
Secondary	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	from time of delivery until time of hospital discharge