Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium

NCT06285409 | Recruiting

• 1 other identifier: 24-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effects of drugs called "uterotonics" that help with the contraction of the uterus after a baby is born. This uterine contraction is very important to stop the bleeding after delivery. An uncontracted uterine state is called "uterine atony", which can lead to an excessive amount of post-delivery bleeding. Carbetocin is an uterotonic drug that works well to prevent post-delivery bleeding. In some cases, carbetocin is not enough to contract the uterus, and ongoing bleeding continues. When that happens, there are other uterotonic medications that can be used. In this study, we aim to find which uterotonic drug, amongst those available (oxytocin, carbetocin, ergometrine or carboprost), is more effective to lower the risk of post-delivery bleeding once carbetocin has already been administered. This study will be done by using a very small sample of uterine tissue, taken from the incision site, following delivery by cesarean section. The sample is taken to the laboratory and will be exposed to carbetocin followed by other uterotonic drugs. The information obtained from this study will help modify the treatment for uterine atony and post-delivery bleeding to lower the risk further.

Conditions

Postpartum Hemorrhage

Keywords

carbetocin; duratocin; oxytocin; uterine contraction

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 (5)

Carbetocin

ACTIVE COMPARATOR

Dose-response testing with increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M

Drug: Carbetocin; Drug: Oxytocin

Oxytocin

ACTIVE COMPARATOR

Dose-response testing with increasing concentrations of oxytocin from 10-10 M to 10-5 M.

Drug: Carbetocin; Drug: Oxytocin

Ergometrine

ACTIVE COMPARATOR

Dose-response testing with increasing concentrations of ergometrine from 10-10 M to 10-5 M

Drug: Carbetocin; Drug: Oxytocin; Drug: Ergonovine

Carboprost

ACTIVE COMPARATOR

Dose-response testing with increasing concentrations of carboprost from 10-10 M to 10-5 M

Drug: Carbetocin; Drug: Oxytocin; Drug: Carboprost

Control

PLACEBO COMPARATOR

No drug added to physiological salt solution (PSS).

Drug: Carbetocin; Drug: Oxytocin

Interventions

Carbetocin DRUG

Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).

Also known as: Duratocin

Carbetocin; Carboprost; Control; Ergometrine; Oxytocin

Oxytocin DRUG

Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.

Also known as: Pitocin

Carbetocin; Carboprost; Control; Ergometrine; Oxytocin

Ergonovine DRUG

Increasing concentrations of ergometrine from 10-10 M to 10-5 M

Also known as: Ergometrine

Ergometrine

Carboprost DRUG

Increasing concentrations of carboprost from 10-10 M to 10-5 M

Also known as: Hemabate

Carboprost

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who give written consent to participate in this study
• Patients with gestational age 37-41 weeks
• Non-laboring patients, not exposed to exogenous oxytocin
• Patients requiring elective primary or first repeat CD
• Patients undergoing CD under spinal anesthesia

You may not qualify if:

• Patient refusal
• Patients who require general anesthesia
• Patients in labour and those receiving oxytocin for induction of labour
• Emergency CD
• placenta accreta spectrum disorder
• Patients who have had previous uterine surgery or \>1 previous CD
• Patients with any condition predisposing to uterine atony and PPH (BMI \> 40 kg/m2,
• Patients on medications that could affect myometrial contractility, such as insulin, nifedipine, labetalol or magnesium sulphate.

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

carbetocin; Oxytocin; Ergonovine; Carboprost; carboprost tromethamine

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; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Mrinalini Balki, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mrinalini Balki, MD

CONTACT

416-586-4800; 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: February 22, 2024
• First Posted: February 29, 2024
• Study Start: April 4, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)