Postpartum Complication, Postpartum Hemorrhage
Conditions
Keywords
Postpartum hemorrhage, Carbetocin, Misoprostol, Vaginal delivery, Uterotonic agents, High-risk pregnancy
Brief summary
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.
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.
Interventions
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.
DRUGMisoprostol
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.
Sponsors
Western Galilee Hospital-Nahariya
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postpartum hemorrhage (PPH) | 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. |
| Need for additional uterotonic treatment or surgical intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in hemoglobin level | From admission to 24-48 hours postpartum | Difference between pre-delivery and post-delivery hemoglobin concentration, measured in g/dL. |
| Blood transfusion requirement | Up to 24-48 hours postpartum | Administration of packed red blood cells or other blood products during or after delivery. |
| Maternal adverse effects related to study medications | Within 24 hours after delivery | Occurrence of maternal side effects including diarrhea, shivering, headache, facial flushing, nausea, or vomiting following administration of study medications. |
Contacts
CONTACTNadir Ganem, Dr.
Outcome results
None listed