Double Simultaneous Uterotonic Agents Versus Single Agent Regimen to Prevent Early Postpartum Hemorrhage

A Randomized Controlled Trial of Double Simultaneous Uterotonic Agents (Misoprostol Plus Intravenous Oxytocin) Versus Single Agent Regimen (Intravenous Oxytocin Only) to Prevent Early Postpartum Hemorrhage

To determine the effectiveness of using two medications simultaneously versus one medication, as is standard of care, in preventing early postpartum hemorrhage.

There have been studies that looked at giving two medications and that there were reduced odds of postpartum hemorrhage.

Specific Aim 1: Determine if double simultaneous uterotonic agent regimen (misoprostol and oxytocin) is superior to single agent (oxytocin only) in reducing postpartum hemorrhage.

Specific Aim 2: Determine any potential side effects of a double simultaneous uterotonic agentregimen (misoprostol and oxytocin) versus a single agent (oxytocin only).

Study Overview

• Status: Recruiting
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: IV Oxytocin; Drug: Sublingual Misoprostol

Detailed Description

Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality in the world, accounting for a quarter of all maternal deaths globally. Most cases of PPH can be attributed to uterine atony, failure of the uterus to contract in the immediate postpartum period. Efforts to prevent uterine atony and thereby PPH have focused on active clinical management of the third stage of labor (the period between delivery of the infant and placenta) and the administration of uterotonic agents (medication that induces uterine contraction). Universal standard of care to prevent postpartum hemorrhage, according to the American College of Obstetrics and Gynecologists and World Health Organization includes various dose infusions of oxytocin. Additional uterotonics are given if necessary, according to noted blood loss and uterine tone. The best uterotonic(s), combination, route, and dose, however, remain actively debated. Randomized controlled trials have not proven that misoprostol is superior to oxytocin or methergine to treat postpartum hemorrhage, but it is a medication that is often used conjunctively or after other agents fail. A Cochrane review of treatment of primary postpartum hemorrhage revealed that oxytocin, ergot alkaloids (i.e., methergine), and combined oxytocin-ergot alkaloid administration were equally effective in preventing PPH in the general obstetric population, whereas prostaglandins alone (i.e., misoprostol) were not. In an effort to determine the benefit of a simultaneous double uterotonic agent regimen in the prevention of PPH, the investigators propose to conduct a controlled trial in which women will be randomly assigned to an intervention group (buccal misoprostol and intravenous oxytocin administered simultaneously) versus a control group (standard of care, intravenous oxytocin alone).

• Study Type: Interventional
• Enrollment (Anticipated): 1358
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University
      • Contact: Deidre Lee; Phone Number: 631-444-9324; Email: deidre.lee@stonybrookmedicine.edu
      • Principal Investigator: Jamesa Bernasko, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

- All women 18 years and older admitted to delivery at Stony Brook University hospital who agree to participate in the study

Exclusion Criteria:

• Women under 18 years old
• Women with known coagulation disorders
• Women with planned cesarean hysterectomy
• Women with known placental accreta spectrum disorders
• Women with known allergy to prostaglandins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous Oxytocin only; Patients will receive standard postpartum Oxytocin IV per protocol	Drug: IV Oxytocin; 40 units IV Oxytocin in 1000 mL normal saline
Experimental: Misoprostol plus intravenous Oxytocin; Patients will receive standard postpartum Oxytocin IV per protocol and also be given Misoprostol 400 mcg sublingual	Drug: IV Oxytocin; 40 units IV Oxytocin in 1000 mL normal saline; Drug: Sublingual Misoprostol; Misoprostol 400 mcg sublingual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if double simultaneous uterotonic agent regimen (misoprostol and oxytocin) is superior to single agent (oxytocin only) in changing postpartum hemorrhage blood loss volume.	Determine if double simultaneous uterotonic agent regimen (misoprostol and oxytocin) is superior to single agent (oxytocin only) in changing postpartum hemorrhage.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine serious adverse outcomes of a double simultaneous uterotonic agent regimen (misoprostol and oxytocin) versus a single agent (oxytocin only) that is documented in the medical record.	Determine any potential side effects of a double simultaneous uterotonic agent regimen (misoprostol and oxytocin) versus a single agent (oxytocin only).	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Stony Brook University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 16, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Oxytocin; Misoprostol
• Other Study ID Numbers: IRB2021-00142

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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.: No