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

Post Partum Hemorrhage Clinical Trial

Official title:

Comparative Efficacy of Carbetocin and Oxytocin in Parturients at Risk of Atonic Postpartum Hemorrhage Undergoing Elective Cesarean Delivery: a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06333340
• Other study ID #: 24-03
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2024
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Contact: Mrinalini Balki, MD
• Phone: 416-586-4800
• Email: mrinalini.balki[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion criteria - Any one or more of the risk factors for uterine atony:

• 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
• Hypertensive disease (chronic hypertension or severe 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

Related Conditions & MeSH terms

• Hemorrhage
• Post Partum Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of parturients requiring additional uterotonic agents intraoperatively	The proportion of patients who are administered additional uterotonic agents intraoperatively will be divided by the total number of patients assigned to the same treatment arm, for each of the 2 groups: oxytocin and carbetocin.	90 minutes
Secondary	Uterine Tone 3 minutes	The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 3 minutes, from the completion of delivery of the drug, utilizing a verbal numeric rating scale of 0-10.	3 minutes
Secondary	Uterine Tone 5 minutes	The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 5 minutes, from the completion of delivery of the drug, utilizing a verbal numeric rating scale of 0-10.	5 minutes
Secondary	Uterine Tone 10 minutes	The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 10 minutes, from the completion of delivery of the drug, utilizing a verbal numeric rating scale of 0-10.	10 minutes
Secondary	Calculated blood loss (CBL)	Blood loss will be calculated through the difference in hematocrit values assessed prior to and at the end of 24 hours after the cesarean section.	24 hours
Secondary	Semi-quantitative blood loss (SQBL)	Blood loss measured in the operating room by volume (ml)	2 hours
Secondary	Presence of blood transfusion	Number of units of blood product administered post-delivery	24 hours
Secondary	Number of patients with ICU admission	Admission to the intensive care unit for bleeding post partum	24 hours
Secondary	Number of patients with conservative surgical methods to manage post partum hemorrhage	Bakri balloon/B-Lynch sutures used intraoperatively	2 hours
Secondary	Number of patients with radiological methods used to manage post partum hemorrhage	Uterine artery embolization used intraoperatively.	2 hours
Secondary	Number of patients with surgical post partum hemorrhage management measures	Re-exploration for bleeding/uterine artery ligation/hysterectomy	2 hours
Secondary	Number of patients with hypotension defined as systolic blood pressure less than 80% of baseline	Systolic blood pressure < 80% of baseline, at any time during surgery	2 hours
Secondary	Number of patients with hypertension defined as systolic blood pressure greater than 120% of baseline	Systolic blood pressure > 120% of baseline, at any time during surgery	2 hours
Secondary	Number of patients with tachycardia defined as heart rate greater than 130% of baseline	Heart rate > 130% of baseline, at any time during surgery	2 hours
Secondary	Number of patients with bradycardia defined as heart rate less than 70% of baseline	Heart rate < 70% of baseline, at any time during surgery	2 hours
Secondary	Presence of ventricular tachycardia: ECG	Presence of ventricular tachycardia as recorded by ECG, at any time during surgery	2 hours
Secondary	Presence of atrial fibrillation: ECG	Presence of atrial fibrillation as recorded by ECG, at any time during surgery	2 hours
Secondary	Presence of atrial flutter: ECG	Presence of atrial flutter as recorded by ECG, at any time during surgery	2 hours
Secondary	Presence of nausea: questionnaire	The presence of nausea at any time during surgery, as reported by the patient	2 hours
Secondary	Presence of vomiting: questionnaire	The presence of vomiting at any time during surgery, as reported by the patient	2 hours
Secondary	Number of patients with chest pain: questionnaire	Any presence of chest pain, at any time during surgery, as reported by the patient	2 hours
Secondary	Number of patients with shortness of breath: questionnaire	Any presence of shortness of breath, at any time during surgery, as reported by the patient.	2 hours
Secondary	Number of patients with headache: questionnaire	Any presence of headache, at any time during surgery, as reported by the patient.	2 hours
Secondary	Number of patients with flushing: questionnaire	Any presence of flushing, at any time during surgery.	2 hours