Carbetocin vs Misoprostol for Postpartum Hemorrhage Prevention

January 13, 2026 updated by: Dr Raneen Abu Shqara, Western Galilee Hospital-Nahariya

Carbetocin Versus Misoprostol for the Prevention of Postpartum Hemorrhage After Vaginal Delivery in Women With Risk Factors: A Prospective Randomized Study

Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide, particularly among women with known risk factors. Uterotonic agents are routinely administered after vaginal delivery to prevent excessive bleeding. Carbetocin, a long-acting oxytocin analogue, and misoprostol are both used for this purpose, but comparative data in high-risk vaginal deliveries remain limited.

This prospective randomized study aims to compare the effectiveness and safety of intravenous carbetocin versus rectal misoprostol for the prevention of postpartum hemorrhage in women with risk factors undergoing vaginal delivery at Galilee Medical Center. The primary outcome is the incidence of postpartum hemorrhage. Secondary outcomes include the need for additional uterotonic agents or surgical interventions, changes in hemoglobin levels, blood transfusion requirements, and maternal adverse effects.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Postpartum hemorrhage (PPH), most commonly caused by uterine atony, remains a major contributor to maternal morbidity and mortality. Women with established risk factors-such as grand multiparity, prior PPH, prolonged labor, fetal macrosomia, polyhydramnios, chorioamnionitis, or prolonged oxytocin exposure-are at particularly increased risk following vaginal delivery.

Active management of the third stage of labor using uterotonic medications is the cornerstone of PPH prevention. Oxytocin is widely used but has a short half-life, often requiring repeated dosing or continuous infusion. Carbetocin is a synthetic oxytocin analogue with a longer half-life and sustained uterotonic effect, which may offer improved prophylaxis against PPH. Misoprostol, a prostaglandin E1 analogue, is also commonly used due to its low cost, ease of administration, and stability, although it is associated with gastrointestinal and thermoregulatory side effects.

While carbetocin has demonstrated superiority over oxytocin in cesarean deliveries, evidence comparing carbetocin with misoprostol in high-risk vaginal deliveries is limited. This prospective, randomized, single-center study will enroll women at term with singleton pregnancies and predefined risk factors for postpartum hemorrhage. Participants will be randomized in a 1:1 ratio to receive either intravenous carbetocin (100 µg) or rectal misoprostol (1000 µg) with standard oxytocin after placental delivery.

The primary outcome is the occurrence of postpartum hemorrhage. Secondary outcomes include the need for additional uterotonic agents, blood transfusion, uterine revision or manual placental removal, changes in hemoglobin levels before and after delivery, duration of maternal hospitalization, and maternal adverse effects such as diarrhea, shivering, headache, and facial flushing.

This study aims to provide high-quality prospective data to guide the optimal prophylactic uterotonic strategy for women at increased risk of postpartum hemorrhage following vaginal delivery.

Study Type

Interventional

Enrollment (Estimated)

146

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Women aged 18 years or older
  • Singleton pregnancy
  • Gestational age 37-42 weeks
  • Cephalic presentation
  • Vaginal delivery
  • Presence of one or more risk factors for postpartum hemorrhage, including:
  • Grand multiparity (≥5 previous deliveries)
  • History of postpartum hemorrhage
  • History of manual removal of placenta
  • Estimated fetal weight ≥4,000 grams
  • Polyhydramnios
  • Chorioamnionitis
  • Prolonged oxytocin use during labor (third augmentation cycle or more)
  • Eligible for prophylactic uterotonic therapy after delivery
  • Provided written informed consent

Exclusion Criteria

  • Multiple gestation
  • Known major fetal anomalies
  • Intrauterine fetal demise (IUFD)
  • Contraindication to vaginal delivery
  • Known hypersensitivity to carbetocin, misoprostol, or oxytocin
  • Known coagulation disorders requiring alternative management
  • Planned cesarean delivery
  • Participation in another interventional study that may affect postpartum bleeding outcomes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Carbetocin arm
Participants in this arm will receive intravenous carbetocin (100 micrograms) immediately after placental delivery for the prevention of postpartum hemorrhage following vaginal delivery. Carbetocin will be administered as part of active management of the third stage of labor in women at increased risk for postpartum hemorrhage.
Drug: Carbetocin 100 Microgram/mL Solution for Injection
Participants randomized to this intervention will receive intravenous carbetocin 100 micrograms administered immediately after placental delivery as prophylaxis for postpartum hemorrhage following vaginal delivery. Carbetocin is a long-acting synthetic analogue of oxytocin and is used as part of active management of the third stage of labor in women at increased risk for postpartum hemorrhage.
Active Comparator: Misoprostol arm
Participants in this arm will receive rectal misoprostol (1000 micrograms) immediately after placental delivery, in addition to intravenous oxytocin, for the prevention of postpartum hemorrhage following vaginal delivery. This regimen represents an accepted uterotonic prophylaxis strategy for women at increased risk for postpartum hemorrhage.
Drug: Misoprostol
Participants randomized to this intervention will receive rectal misoprostol 1000 micrograms immediately after placental delivery for the prevention of postpartum hemorrhage following vaginal delivery. In accordance with standard practice, intravenous oxytocin 10 units will also be administered as part of active management of the third stage of labor in women at increased risk for postpartum hemorrhage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postpartum hemorrhage (PPH)
Time Frame: Within 24 hours after delivery
Postpartum hemorrhage defined as estimated blood loss ≥1,000 mL within 24 hours after vaginal delivery, or any bleeding associated with hemodynamic instability requiring medical or surgical intervention, according to institutional protocol.
Within 24 hours after delivery
Need for additional uterotonic treatment or surgical intervention
Time Frame: Within 24 hours of delivery
Requirement for additional uterotonic agents (including oxytocin infusion, methylergonovine, carboprost, or misoprostol), uterine massage, uterine revision, or surgical intervention for management of postpartum bleeding.
Within 24 hours of delivery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in hemoglobin level
Time Frame: From admission to 24-48 hours postpartum
Difference between pre-delivery and post-delivery hemoglobin concentration, measured in g/dL.
From admission to 24-48 hours postpartum
Blood transfusion requirement
Time Frame: Up to 24-48 hours postpartum
Administration of packed red blood cells or other blood products during or after delivery.
Up to 24-48 hours postpartum
Maternal adverse effects related to study medications
Time Frame: Within 24 hours after delivery
Occurrence of maternal side effects including diarrhea, shivering, headache, facial flushing, nausea, or vomiting following administration of study medications.
Within 24 hours after delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Western Galilee Hospital-Nahariya

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 31, 2026

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

January 13, 2026

First Submitted That Met QC Criteria

January 13, 2026

First Posted (Actual)

January 20, 2026

Study Record Updates

Last Update Posted (Actual)

January 20, 2026

Last Update Submitted That Met QC Criteria

January 13, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0206-25-NHR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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