High Or Low Dose pOstpartUm Oxytocin at the Time of Cesarean Birth (HOLDOUT)

A Pilot Study of High Or Low Dose pOstpartUm Oxytocin at the Time of Cesarean Birth (HOLDOUT Pilot)

This is a study to investigate whether it is feasible to conduct a randomized controlled trial (RCT) of a high dose of oxytocin versus the standard low-dose oxytocin. Further the investigators, aim to assess whether there are differences in health outcomes between both arms of the study.

Study Overview

• Status: Withdrawn
• Conditions: Pregnancy Complications; Cesarean Section Complications; Postpartum Hemorrhage
• Intervention / Treatment: Drug: Oxytocin

Detailed Description

Due to risks of postpartum hemorrhage, defined by the American College of Obstetricians and Gynecologists, as an estimated or quantitative blood loss of greater than 1000 milliliters, uterotonics, or medications aimed at increasing uterine tone and reducing blood loss at the time of birth, are commonly administered. Based on a Cochrane network meta-analysis, most organizations endorse the administration of 10 international units (IU) of oxytocin during delivery. However, the World Health Organization specifies that during a cesarean birth, the 10 IU should be administered using a bolus dose and an infusion, though an optimal infusion rate has yet to be agreed upon.

The use of a higher rate of oxytocin may confer a reduction in overall blood loss and subsequent maternal health outcomes (e.g., postoperative anemia, hypotension) and healthcare resource utilization (e.g., need for additional uterotonics and surgical procedures to control bleeding, administration of blood products). However, it is unknown whether it is feasible to conduct a randomized controlled trial to investigate the use of high (i.e., oxytocin rate of 900 mL/hr immediately after the delivery of the placenta) versus low-dose oxytocin (i.e., 300 mL/hr for planned cesarean births or 600 mL/hr for intrapartum cesarean births).

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria.

• Age 18 or greater
• English or Spanish speaking
• Individuals undergoing a scheduled or unscheduled cesarean delivery

Exclusion criteria

• Patient on therapeutic anticoagulation
• Patient with hypertensive disorder of pregnancy or chronic hypertension
• Patient with preexisting bleeding disorder
• Patient with preexisting cardiac disease
• Patient with severe asthma, defined as the need for two or more agents for disease control, or bronchospasm
• Patient undergoing planned cesarean hysterectomy

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
Experimental: High-dose oxytocin; 900 mL/hr (54 units/hr) intravenously for the duration of the cesarean delivery	Drug: Oxytocin; Oxytocin is a synthetic molecule used to reduce the likelihood of postpartum hemorrhage.
Active Comparator: Low-dose oxytocin; For unlabored cesarean births: 300 mL/hr (18 IU/hr), with a maximum rate of 900 mL/hr (54 units/hr) intravenously for the duration of the cesarean delivery For laboring cesarean births: 600 mL/hr (36 IU/hr), with a maximum rate of 900 mL/hr (54 units/hr) intravenously for the duration of the cesarean delivery	Drug: Oxytocin; Oxytocin is a synthetic molecule used to reduce the likelihood of postpartum hemorrhage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screen failure rate	Number of individuals who are eligible for the study but do not consent to participate	Within 8 hours prior to cesarean delivery
Fidelity rate	Frequency of fidelity to the trial	Within 8 hours prior to cesarean delivery
Trial retention rate	Frequency of participant completion of all study visits	Up to 6 weeks after cesarean delivery
Acceptability of the intervention	Frequency of acceptability of the intervention by both participants and their providers	Up to 6 weeks after cesarean delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal flushing		During and up to 6 hours after cesarean delivery
Maternal hypotension	Mean arterial blood pressure less than 65 mmHg	During and up to 6 hours after cesarean delivery
Maternal nausea/vomiting		During and up to 6 hours after cesarean delivery
Myocardial ischemia		During and up to 24 hours after cesarean delivery
Cardiac arrhythmia		During and up to 24 hours after cesarean delivery
Quantitative blood loss greater than 1 liter		Within 24 hours after cesarean delivery
Need for blood product transfusion, inclusive of type and number of blood products transfused		Within 4 days after cesarean delivery
Frequency of increase in oxytocin rate in low-dose arm		During and up to 6 hours after cesarean delivery
Additional use of uterotonics and/or tranexamic acid		During and up to 24 hours after cesarean delivery
Placement of intrauterine balloon tamponade or suction device		During and up to 24 hours after cesarean delivery
Surgical management of hemorrhage, inclusive of hysterectomy		During and up to 24 hours after cesarean delivery
Intensive care unit admission		During and up to 24 hours after cesarean delivery
Maternal death		During and up to 6 weeks after cesarean delivery
Readmission to the hospital or reoperation		Up to 6 weeks after cesarean delivery

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Medical College of Wisconsin
• Investigators: Principal Investigator: Anna Palatnik, MD, Medical College of Wisconsin; Principal Investigator: Ashish Premkumar, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: oxytocin; postpartum hemorrhage; cesarean delivery
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Pregnancy Complications; Postpartum Hemorrhage; Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB24-0398

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared by the us, the investigators, upon request by other researchers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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.: Yes