Effect of Extracellular Calcium on Carbetocin Mediated Contractility in Human Myometrium

NCT06930391 | Recruiting

• 1 other identifier: 25-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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)

Keywords

carbetocin; calcium; uterine contraction; cesarean delivery

Outcome Measures

Primary Outcomes (1)

• Motility index

  Motility index (MI) is a calculated outcome, based on the formula: frequency/(10 x amplitude). Frequency and amplitude are secondary outcome measures as described below. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

  4 hours

Secondary Outcomes (3)

• Amplitude of contraction

  4 hours

• Frequency of contraction

  4 hours

• Integrated area under response curve (AUC)

  4 hours

Study Arms (6)

Calcium 1.25nM with NO oxytocin pre-exposure

ACTIVE COMPARATOR

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

Drug: Carbetocin; Drug: Calcium

Calcium 2.5nM with NO oxytocin pre-exposure

ACTIVE COMPARATOR

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

Drug: Carbetocin; Drug: Calcium

Calcium 5.0nM with NO oxytocin pre-exposure

ACTIVE COMPARATOR

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

Drug: Carbetocin; Drug: Calcium

Calcium 1.25nM with oxytocin pre-exposure

ACTIVE COMPARATOR

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

Drug: Oxytocin; Drug: Carbetocin; Drug: Calcium

Calcium 2.5nM with oxytocin pre-exposure

ACTIVE COMPARATOR

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

Drug: Oxytocin; Drug: Carbetocin; Drug: Calcium

Calcium 5.0nM with oxytocin pre-exposure

ACTIVE COMPARATOR

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

Drug: Oxytocin; Drug: Carbetocin; Drug: Calcium

Interventions

Oxytocin DRUG

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

Calcium 1.25nM with oxytocin pre-exposure; Calcium 2.5nM with oxytocin pre-exposure; Calcium 5.0nM with oxytocin pre-exposure

Carbetocin 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 1.25nM with NO oxytocin pre-exposure; Calcium 1.25nM with oxytocin pre-exposure; Calcium 2.5nM with NO oxytocin pre-exposure; Calcium 2.5nM with oxytocin pre-exposure; Calcium 5.0nM with NO oxytocin pre-exposure; Calcium 5.0nM with oxytocin pre-exposure

Calcium DRUG

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

Calcium 1.25nM with NO oxytocin pre-exposure; Calcium 1.25nM with oxytocin pre-exposure; Calcium 2.5nM with NO oxytocin pre-exposure; Calcium 2.5nM with oxytocin pre-exposure; Calcium 5.0nM with NO oxytocin pre-exposure; Calcium 5.0nM with oxytocin pre-exposure

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

RECRUITING

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Oxytocin; carbetocin; Calcium

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Central Study Contacts

Mrinalini Balki, MD

CONTACT

416-586-480; mrinalini.balki@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 16, 2025
• Study Start: September 15, 2025
• Primary Completion: June 1, 2026
• Study Completion: June 1, 2026
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)