Carbetocin vs. Oxytocin at Elective Cesarean Section

Postpartum Hemorrhage Clinical Trial

Official title:

Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03168698
• Other study ID #: 17-01
• Status: Completed
• Phase: N/A
• Start date: May 25, 2017
• Est. completion date: December 18, 2020

Study information

• Verified date: February 2021
• Source: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study investigators are comparing 2 drugs (oxytocin and carbetocin) at 2 different dosages, to help prevent serious bleeding (hemorrhage) after cesarean deliveries. These drugs are used routinely to help contract the uterus and keep it contracted after the delivery of the baby and placenta; this reduces the amount of blood you might lose. At Mount Sinai Hospital, currently oxytocin is used, but its effect on the uterus is much shorter than that of carbetocin. Internationally, there is no consensus as to what the most effective drug to use is and at which dose. The Society of Obstetricians and Gynaecologists of Canada has recently revised its guidelines to suggest 100 micrograms (mcg) of carbetocin as the drug of choice at elective cesarean section. Guidelines from the United Kingdom and the United States currently suggest oxytocin at various doses as the drug of choice at elective cesarean sections. Previous studies at Mount Sinai Hospital have shown that lower doses of oxytocin, 0.35 International Units (IU), and carbetocin, 20 mcg, may be as effective as the higher recommended doses. The investigators plan to conduct a large study to confirm these findings so that they can use the most appropriate dose in the future. Furthermore, the investigators hope to demonstrate that side effects are lower with the lower dose regimens.

Description:

Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most commonly used uterotonic drug to prevent and treat PPH in the world. However, oxytocin has a very short duration of action, requiring a continuous infusion to achieve sustained uterotonic activity. Moreover, large doses are associated with adverse effects like hypotension, nausea, vomiting, dysrhythmias and ST changes. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of the longer acting carbetocin at elective cesarean section to promote uterine contraction. In multiple studies performed at Mount Sinai Hospital, we have shown that smaller doses of oxytocin (ED 90 0.35 IU) and carbetocin (ED 90 14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. No study has directly compared the high dose regimens with the low dose regimens; therefore a large double-blind randomized controlled trial is necessary to show the non-inferiority of the lower doses of both drugs.

There is a lack of consensus as to what the optimal uterotonic regime is globally. Furthermore, variability in the international guidelines regarding the choice of first line uterotonic in prevention of PPH adds to the confusion. With the widespread availability of carbetocin in some of the developed countries, including Canada, the question of which uterotonic to adopt and at which dose becomes even more difficult to ascertain. Studies that have currently been published suggest the ED90 doses of carbetocin and oxytocin provide adequate uterine contraction with possibly fewer side effects associated with the lower dosed regimens. These advantages may provide a better safety profile and patient satisfaction. To the best of our knowledge, no studies have compared the low doses (ED90) of oxytocin vs. carbetocin, or low (ED90) vs high (conventional) doses of the two drugs in the setting of elective cesarean section. The results of this study will provide evidence on the efficacy and safety of the ED90 dosing compared directly to the higher dosing of both drugs.

Our hypothesis is that the ED90 doses of carbetocin and oxytocin will not be inferior to the higher dosing as determined by the intensity of uterine contraction using a VNRS in women undergoing elective cesarean section. We anticipate that the intensity of uterine contraction using the VNRS at 2 minutes post administration of all drugs will fall within the predetermined margin to signify non-inferiority of all regimens.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: December 18, 2020
• Est. primary completion date: December 17, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Elective cesarean section under spinal anesthesia.

• Written informed consent to participate in this study.

• Full-term pregnancy

• Non labouring patients

Exclusion Criteria:

• Refusal to give written informed consent.

• Allergy or hypersensitivity to carbetocin or oxytocin.

• Labouring patients

• Need for general anesthesia

• Conditions that predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, preeclampsia, eclampsia, macrosomia, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.

• Hepatic, renal, and cardiovascular disease.

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Carbetocin
Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
• Oxytocin
Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Locations

Country	Name	City	State
Canada	McMaster University Medical Centre (MUMC)	Hamilton	Ontario
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 2 minutes	Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 2 minutes after completion of injection of the bolus study drug.	2 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 minutes
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 minutes
Secondary	Additional uterotonics - operating room	The use of additional uterotonic agents in the operating room	1 hour
Secondary	Additional uterotonics - 24 hours	The use of additional uterotonic agents at any time after admission to the recovery room and up to 24 hours post delivery	24 hours
Secondary	Estimated blood loss	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	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