Effect of Extracellular Calcium on Carbetocin Mediated Contractility in Human Myometrium

NCT ID: NCT06930391

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-15
• Study Completion Date: 2026-06-30

Brief Summary

Postpartum hemorrhage (PPH) continues to be an increasing problem globally. Uterotonics play an essential role in the pharmacological management of uterine atony. Carbetocin, a long acting analog of oxytocin has been recommended as a first line uterotonic for PPH prophylaxis at cesarean delivery. Considering many woman have associated comorbidities and are at high risk of PPH, finding alternative pharmacological agents is essential. Calcium is a key factor for myometrial contractions and calcium blood levels can be low at the end of pregnancy. Both hypocalcemia and hypercalcemia could lead to a decrease in myometrial contractions. It is already been demonstrated that in both desensitized and naïve myometrium, normocalcemia provides a better uterine tone compared to hypo and hypercalcemia when oxytocin is given as the first uterotonic drug.

Currently, the role of extracelullar calcium in carbetocin- induced contractility is unknown. This will be the first ex vivo study to test the effects of extracellular calcium on oxytocin pretreated and naive myometrium. The results of this study will provide evidence on the use of this safe drug in clinical practice, particularly in women with labour arrest, and provide alternative pharmacological strategies to both prevention and treatment of PPH, thus improving our clinical practice.

The investigators hypothesize that extracellular normocalcemia would provide superior carbetocin-mediated contractility in both naive and oxytocin-pretreated myometrium compared with hypercalcemia and hypocalcemia.

Conditions

Postpartum Hemorrhage (Primary)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Calcium 1.25nM with NO oxytocin pre-exposure

Dose-response testing with 1.25nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure

Group Type: ACTIVE_COMPARATOR

Carbetocin

Intervention Type: DRUG

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Calcium

Intervention Type: DRUG

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Calcium 2.5nM with NO oxytocin pre-exposure

Dose-response testing with 2.5nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure

Group Type: ACTIVE_COMPARATOR

Carbetocin

Intervention Type: DRUG

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Calcium

Intervention Type: DRUG

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Calcium 5.0nM with NO oxytocin pre-exposure

Dose-response testing with 5.0nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure

Group Type: ACTIVE_COMPARATOR

Carbetocin

Intervention Type: DRUG

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Calcium

Intervention Type: DRUG

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Calcium 1.25nM with oxytocin pre-exposure

Dose-response testing with 1.25nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.

Carbetocin

Intervention Type: DRUG

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Calcium

Intervention Type: DRUG

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Calcium 2.5nM with oxytocin pre-exposure

Dose-response testing with 2.5nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.

Carbetocin

Intervention Type: DRUG

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Calcium

Intervention Type: DRUG

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Calcium 5.0nM with oxytocin pre-exposure

Dose-response testing with 5.0nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.

Carbetocin

Intervention Type: DRUG

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Calcium

Intervention Type: DRUG

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Interventions

Oxytocin

Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.

Intervention Type: DRUG

Carbetocin

Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M

Intervention Type: DRUG

Calcium

Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• non-laboring women with gestational age between 37 to 41 weeks
• not exposed to exogenous oxytocin, scheduled for a primary or first repeat cesarean delivery under neuraxial anesthesia.

Exclusion Criteria

• patients requiring general anesthesia
• more than 1 previous cesarean delivery
• history of uterine atony
• emergency cesarean section in labor
• patients using medications that could affect myometrial contractility such as nifedipine, labetalol, or magnesium sulphate.
• patients with any condition of predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, severe preeclampsia, macrosomia, polyhydroamnios, large uterine fibroids, chorioamnionitis, previous history of postpartum bleeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 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

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Mrinalini Balki, MD

Role: CONTACT

mrinalini.balki@uhn.ca

416-586-480 ext. 5270

Facility Contacts

Mrinalini Balki, MD

Role: primary

mrinalini.balki@uhn.ca

416-586-4800 ext. 5270

Other Identifiers

25-01

Identifier Type: -

Identifier Source: org_study_id