Carbetocin vs Misoprostol for Postpartum Hemorrhage Prevention

Western Galilee Hospital-Nahariya

Status: Not yet enrolling

Conditions: Postpartum Complication; Postpartum Hemorrhage

Treatments: Drug: Carbetocin 100 Microgram/mL Solution for Injection; Drug: Misoprostol

Study type: Interventional

Funder types: Other

Identifiers

NCT07353281

0206-25-NHR

Details and patient eligibility

About

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.

Full 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.

Enrollment: 146 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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146 participants in 2 patient groups

Carbetocin arm

Experimental group

Description:

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.

Treatment:

Drug: Carbetocin 100 Microgram/mL Solution for Injection

Misoprostol arm

Active Comparator group

Description:

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.

Treatment:

Drug: Misoprostol