Oxytocin vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity

Post Partum Hemorrhage Clinical Trial

Official title:

Oxytocin Vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity: Double-blind, Randomised Control, Non-inferiority Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04902729
• Other study ID #: 21-03
• Status: Completed
• Phase: N/A
• Start date: July 20, 2021
• Est. completion date: December 9, 2022

Study information

• Verified date: February 2023
• Source: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most commonly used uterotonic drug for the active management of third stage labor, to reduce the risk of PPH and help deliver the placenta. Carbetocin is currently recommended by the SOGC (Society of Obstetricans & Gynecologists of Canada), and is a relatively newer drug with a longer duration of action. It has been previously demonstrated that women with elevated BMI require higher doses of these drugs to induce adequate uterine contraction and dose finding studies undertaken at Mount Sinai Hospital have shown that the ED 90 in obese patients to be carbetocin 80 mcg and oxytocin 1IU. Furthermore, previous studies have indicated that the use of carbetocin over oxytocin in non-obese popultion is associated with reduced bleeding and requirement of additional uterotonic medications. No study has directly compared the two drugs in obese parturients in a head to head clinical trial; therefore a double-blind randomized controlled trial is necessary to show the non-inferiority of carbetocin against the current standard of care at Mount Sinai hospital, which is oxytocin.

Description:

Obesity in pregnancy is defined as a Body Mass Index (BMI) above 30 kg/m2 and is often cited as a risk factor for PPH after cesarean delivery.

The World Health organization (WHO) recommends that uterotonic medications are routinely administered at cesarean delivery for the active management of the third stage of labor, both to facilitate delivery of the placenta and to reduce the risk of PPH. The optimal regimen for active management of third stage of labor is yet to be fully determined and obesity adds another layer of complexity and risk, with higher doses required to induce adequate uterine contraction. While oxytocin is the most commonly used drug world-wide, multiple agents are available and there is no clear consensus as to which drug should be first choice. Multiple studies have shown that carbetocin is associated with reduced post-partum bleeding, need for blood transfusion and additional uterotonic medications, in the non-obese population.

The results of this study will provide evidence on the non-inferiority of carbetocin when compared directly to the current standard of care at Mount Sinai hospital, which is oxytocin.

The investigators hypothesize that when administered in equipotent doses, carbetocin would be non-inferior to oxytocin in women with BMI ≥40 kg/m2 undergoing elective cesarean delivery.

The investigators hope to prove that the difference between uterine tone elicited by carbetocin falls within the inferiority margin of -1.2 using a verbal numerical rating score.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 9, 2022
• Est. primary completion date: December 8, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• BMI=40 kg/m2

• Elective cesarean delivery under spinal, epidural, or combined spinal-epidural anaesthesia

• Written informed consent

• Full term pregnancy (37+0 to 40+6 weeks gestation)

• Non-labouring patients

Exclusion Criteria:

• Refusal to give written informed consent

• Allergy or hypersensitivity to carbetocin or oxytocin

• Laboring patients

• Need for general anaesthesia

• Conditions that predispose to uterine atony and postpartum haemorrhage including but not limited to:

• Placenta previa

• Multiple gestations

• Preeclampsia

• Eclampsia

• Polyhydramnios

• Uterine fibroids

• Previous history of uterine atony and postpartum bleeding

• Bleeding diathesis

• Hepatic, renal, and cardiovascular disease

Related Conditions & MeSH terms

• Hemorrhage
• Obesity, Morbid
• Post Partum Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Carbetocin
Patient is given carbetocin (80mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
• Oxytocin
Patient is given oxytocin (1IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby, followed by infusion 80 mU/min (40 IU in 1L given at a rate of 120 mL/h).

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	Uterine Tone 3 minutes	The primary outcome will be 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, utilising a VNRS scale of 0-10.	3 minutes
Secondary	Uterine Tone 5 minutes	Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 5 minutes after completion of injection of the bolus study drug.	5 min
Secondary	Uterine Tone 10 minutes	Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 10 minutes after completion of injection of the bolus study drug.	10 min
Secondary	Additional uterotonics - operating room	The use of additional uterotonic agents in the operating room	1-2 hours, length of surgery will vary
Secondary	Additional uterotonics - Post Anesthesia Care Unit (PACU)	The use of additional uterotonic agents at any time after admission to the recovery area (Post Anesthesia Care Unit (PACU)) until transfer to the post partum ward.	4 hours
Secondary	Additional uterotonics - 24 hours	The use of additional uterotonic agents at any time after discharge from the recovery area (Post Anesthesia Care Unit (PACU)) and up to 24 hours post delivery	24 hours
Secondary	Estimated blood loss calculated	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	Estimated blood loss, visual estimate provided by the obstetrician	Blood loss in ml, as reported by the obstetrician at the end of the surgery.	2 hours
Secondary	Hypotension: systolic blood pressure less than 80% of baseline	Systolic blood pressure < 80% of baseline, from drug administration until end of surgery	2 hours
Secondary	Hypertension: systolic blood pressure greater than 120% of baseline	Systolic blood pressure > 120% of baseline, from drug administration until end of surgery	2 hours
Secondary	Tachycardia: heart rate greater than 130% of baseline	Heart rate > 130% of baseline, from drug administration until end of surgery	2 hours
Secondary	Bradycardia: heart rate less than 70% of baseline	Heart rate < 70% of baseline, from drug administration until end of surgery	2 hours
Secondary	Presence of ventricular tachycardia: ECG	Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery	2 hours
Secondary	Presence of atrial fibrillation: ECG	Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery	2 hours
Secondary	Presence of atrial flutter: ECG	Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery	2 hours
Secondary	Presence of nausea: questionnaire	The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient	2 hours
Secondary	Presence of vomiting: questionnaire	The presence of vomiting and number of episodes, from drug administration until end of surgery	2 hours
Secondary	Presence of chest pain: questionnaire	Any presence of chest pain, from drug administration until end of surgery, as reported by the patient	2 hours
Secondary	Presence of shortness of breath: questionnaire	Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient	2 hours
Secondary	Presence of headache: questionnaire	Any presence of headache, from drug administration until end of surgery, as reported by the patient	2 hours
Secondary	Presence of flushing: questionnaire	Any presence of flushing, from drug administration until end of surgery	2 hours