Clinical trial NCT06333340: Comparative Efficacy of Carbetocin and Oxytocin in Parturients at Risk of Atonic Postpartum Hemorrhage Undergoing Elective Cesarean Delivery
Official title: Comparative Efficacy of Carbetocin and Oxytocin in Parturients at Risk of Atonic Postpartum Hemorrhage Undergoing Elective Cesarean Delivery: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post Partum Hemorrhage
Keywords: oxytocin
carbetocin
cesarean delivery
pregnancy
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2024-03-27
Enrollment: 160
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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

Primary outcomes:
measure: Proportion of parturients requiring additional uterotonic agents intraoperatively
timeFrame: 90 minutes
Secondary outcomes:
measure: Uterine Tone 3 minutes
timeFrame: 3 minutes
measure: Uterine Tone 5 minutes
timeFrame: 5 minutes
measure: Uterine Tone 10 minutes
timeFrame: 10 minutes
measure: Calculated blood loss (CBL)
timeFrame: 24 hours
measure: Semi-quantitative blood loss (SQBL)
timeFrame: 2 hours
measure: Presence of blood transfusion
timeFrame: 24 hours
measure: Number of patients with ICU admission
timeFrame: 24 hours
measure: Number of patients with conservative surgical methods to manage post partum hemorrhage
timeFrame: 2 hours
measure: Number of patients with radiological methods used to manage post partum hemorrhage
timeFrame: 2 hours
measure: Number of patients with surgical post partum hemorrhage management measures
timeFrame: 2 hours
measure: Number of patients with hypotension defined as systolic blood pressure less than 80% of baseline
timeFrame: 2 hours
measure: Number of patients with hypertension defined as systolic blood pressure greater than 120% of baseline
timeFrame: 2 hours
measure: Number of patients with tachycardia defined as heart rate greater than 130% of baseline
timeFrame: 2 hours
measure: Number of patients with bradycardia defined as heart rate less than 70% of baseline
timeFrame: 2 hours
measure: Presence of ventricular tachycardia: ECG
timeFrame: 2 hours
measure: Presence of atrial fibrillation: ECG
timeFrame: 2 hours
measure: Presence of atrial flutter: ECG
timeFrame: 2 hours
measure: Presence of nausea: questionnaire
timeFrame: 2 hours
measure: Presence of vomiting: questionnaire
timeFrame: 2 hours
measure: Number of patients with chest pain: questionnaire
timeFrame: 2 hours
measure: Number of patients with shortness of breath: questionnaire
timeFrame: 2 hours
measure: Number of patients with headache: questionnaire
timeFrame: 2 hours
measure: Number of patients with flushing: questionnaire
timeFrame: 2 hours
measure: Additional uterotonics administered up to 24 hours post delivery: questionnaire
timeFrame: 24 hours
measure: Obstetric Quality of Recovery-10 (ObsQoR-10) score 24 hours
timeFrame: 24 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Mrinalini Balki, MD
role: PRINCIPAL_INVESTIGATOR
References: