Comparative Efficacy of Carbetocin and Oxytocin in Parturients at Risk of Atonic Postpartum Hemorrhage Undergoing Elective Cesarean Delivery

NCT ID: NCT06333340

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-14
• Study Completion Date: 2025-12-31

Brief Summary

The goal of this study is to compare 2 medications that are commonly used to prevent excess uterine bleeding (postpartum hemorrhage, or PPH) following cesarean delivery (CD), oxytocin and carbetocin. Most of the trials evaluating the preventative role of oxytocin and carbetocin after CD have focused on patient with low-risk of PPH.

This trial will focus on patients that are at increased risk of PPH, with risk factors such as: multiple gestation (twins, or more multiples), large baby, polyhydramnios (excess amniotic fluid), history of PPH, body mass index greater than 40, diabetes mellitus, hypertension, and placenta previa.

The investigators hypothesize that carbetocin would be more effective than an oxytocin regimen in reducing the risk of PPH in patients undergoing CD with any of the biological high-risk factors.

Detailed Description

Postpartum hemorrhage (PPH) is a potentially life-threatening complication and one of the leading causes of maternal mortality. It has been estimated that one in every five maternal deaths occurs due to PPH globally. Primary PPH is predominantly caused by uterine atony or inadequate contraction of the uterus after childbirth. Active management of the third stage of labor involves prophylactic administration of a uterotonic agent before delivery of the placenta, as well as delayed cord clamping and controlled traction of the umbilical cord. The uterotonic administration remains the most essential component in terms of preventing PPH.

Oxytocin, a synthetic pituitary hormone, is the most commonly used first-line uterotonic drug. However, because of the short half-life (3-17 min), a continuous intravenous infusion is necessary to maintain uterotonic activity. Carbetocin is a synthetic oxytocin analog that binds with a similar affinity to the oxytocin receptors in the myometrium. Carbetocin produces stronger and more sustained action compared to oxytocin and has a longer half-life than oxytocin, thus reducing the requirement for an infusion after the initial dose. Recently published guidelines from the Society of Obstetrics and Gynecology (SOGC) have stated that Carbetocin should be considered as a first-line agent for the prevention of PPH after cesarean delivery (CD). The international consensus statement on the use of uterotonic agents has also recommended carbetocin as an alternative to oxytocin infusion during CD due to its longer duration of action.

Trials comparing carbetocin with oxytocin in CD have shown mixed results on superiority of carbetocin over oxytocin for the need for additional uterotonics and amount of blood loss, however, no significant effect on blood loss >1000 ml could be found. Most of the trials evaluating the prophylactic role of oxytocin and carbetocin after CD have focused on the low-risk PPH population. The incidence of biological risk factors for uterine atony such as multiple gestation (due to assisted reproductive techniques), and obesity has progressively increased in developed countries. There is still a lack of high-quality trials on the efficacy of carbetocin in high-risk parturients undergoing CD.

In this study, the investigators aim to compare the efficacy of carbetocin 100 mcg with oxytocin 5 IU bolus followed by continuous infusion of 250 mIU/min over 4 hours at elective CD in parturients with risk factors for uterine atony.

The comparative data is still lacking for both the agents as first-line uterotonics for patients having a high risk for uterine atony undergoing cesarean delivery. The result of this trial regarding the relative uterotonic efficacy and safety of the standardized prophylactic doses of both agents (carbetocin and oxytocin) will form the evidence base for future guidelines in high-risk parturients.

Conditions

Post Partum Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oxytocin 5IU

IV oxytocin 5 IU diluted in 10 mL normal saline over 1 min followed by continuous infusion of 250 mIU/min over 4 hours.

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Patient is given oxytocin 5 IU diluted in 10 mL normal saline, administered intravenously over 1 min, followed by continuous infusion of 250 mIU/min over 4 hours.

Carbetocin 100mcg

IV carbetocin 100 mcg diluted in 10 mL normal saline over 1 min followed by placebo infusion for 4 hours after the delivery of the fetus.

Group Type: ACTIVE_COMPARATOR

Carbetocin

Intervention Type: DRUG

Patient is given carbetocin 100 mcg diluted in 10 mL normal saline, administered intravenously over 1 min, followed by placebo infusion for 4 hours.

Interventions

Oxytocin

Patient is given oxytocin 5 IU diluted in 10 mL normal saline, administered intravenously over 1 min, followed by continuous infusion of 250 mIU/min over 4 hours.

Intervention Type: DRUG

Carbetocin

Patient is given carbetocin 100 mcg diluted in 10 mL normal saline, administered intravenously over 1 min, followed by placebo infusion for 4 hours.

Intervention Type: DRUG

Other Intervention Names

Pitocin; Duratocin

Eligibility Criteria

Inclusion Criteria

• Overdistended uterus due to:

• Polyhydramnios (amniotic fluid index >24 cm)
• Fetal macrosomia reported on prenatal ultrasound >90th centile or > 4000 gm
• Multiple gestation
• History of uterine atony/PPH (documented with blood loss of >1000 ml, blood transfusion, use surgical methods such as Bakri balloon, B-Lynch sutures, uterine artery ligation or embolization)
• Obesity with body mass index (BMI) >40 kg/m2
• Diabetes mellitus on treatment
• Preeclampsia on treatment
• Placenta previa

Exclusion Criteria

• Valvular heart disease, arrhythmias, or heart failure
• Placenta accreta spectrum
• Bleeding disorder
• Anemia (<100 g/dl)
• Allergy or sensitivity to oxytocin or carbetocin

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mrinalini Balki, MD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Mrinalini Balki, MD

Role: CONTACT

mrinalini.balki@uhn.ca

416-586-4800 ext. 5270

Facility Contacts

Mrinalini Balki, MD

Role: primary

mrinalini.balki@uhn.ca

416-586-4800 ext. 5270

Other Identifiers

24-03

Identifier Type: -

Identifier Source: org_study_id