In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol

NCT03434444 | Completed

• 1 other identifier: 18-04
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The rates of cesarean deliveries (CD) and postpartum hemorrhage (PPH) are on the rise, with failed induction and augmentation of labor as major contributing factors. Oxytocin is commonly used for labor induction, as well as during the third stage of labor to minimize the risk of primary PPH. At delivery, it is imperative that the uterus responds effectively to parenteral oxytocin. Poor response to oxytocin following delivery is commonly due to prolonged labor with oxytocin augmentation that is known to "desensitize" the myometrium. Despite the option of several second line uterotonic agents, none of them are as effective as oxytocin in controlling PPH. Given that poor uterine muscle contraction is the root cause of both failed induction or augmentation (leading to a CD in labor) and uterine atony (leading to PPH), there is an urgent and clinically important need to investigate novel methods to enhance oxytocin-induced myometrial contractions. Propranolol, a beta adrenergic receptor agonist, has the potential to improve myometrial contractions by virtue of its ability to inhibit catecholamine production. The investigators plan to investigate the effects of propranolol in both naive and desensitized myometrium, in order to better understand its potential role in improving labor induction and reducing the risk of PPH following oxytocin exposure during labor. The investigators hypothesize that propranolol is likely to potentiate the action of oxytocin upon human myometrium, to ultimately help improve the success of labor induction/augmentation and treatment of PPH.

Conditions

Postpartum Hemorrhage

Keywords

propranolol; oxytocin; uterine contraction

Outcome Measures

Primary Outcomes (1)

• Motility index

  Motility index (MI) takes into account both the amplitude and frequency of the myometrial contraction. It is a calculated outcome, based on the formula: frequency/(10 x amplitude). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

  3 hours

Secondary Outcomes (3)

• Amplitude of contraction

  3 hours

• Frequency of contraction

  3 hours

• Integrated area under response curve (AUC)

  3 hours

Study Arms (6)

Low Dose Oxytocin

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M)

Drug: Oxytocin

Propranolol

ACTIVE COMPARATOR

The myometrial samples are bathed in a propranol solution at 10 -6M

Drug: Propranolol

Propranolol + low dose oxytocin

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) plus propranol (10 -6M)

Drug: Oxytocin; Drug: Propranolol

High Dose Oxytocin

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M)

Drug: Oxytocin

High Dose Oxytocin, Propranolol-pretreated

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution (10 -5M) plus propranolol (10 -6M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M)

Drug: Oxytocin; Drug: Propranolol

High dose oxytocin + propranolol

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) plus propranolol (10 -6M)

Drug: Oxytocin; Drug: Propranolol

Interventions

Oxytocin DRUG

Oxytocin in solution, ranging from 10 -12M to 10 -5M

Also known as: pitocin

High Dose Oxytocin; High Dose Oxytocin, Propranolol-pretreated; High dose oxytocin + propranolol; Low Dose Oxytocin; Propranolol + low dose oxytocin

Propranolol DRUG

Propranolol in solution, 10-6M

High Dose Oxytocin, Propranolol-pretreated; High dose oxytocin + propranolol; Propranolol; Propranolol + low dose oxytocin

Eligibility Criteria

• Age: 16 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), 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 primary Cesarean delivery or first repeat Cesarean delivery

You may not qualify if:

• Patients who refuse to give written informed consent
• Patients who require general anesthesia
• Patients who had previous uterine surgery or more than one previous Cesarean delivery
• Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding
• Emergency Cesarean section in labor
• Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulfate

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

Related Publications (1)

• Balki M, Miller LM, Caliaperumal J, Wang S, Huszti E, Kingdom JC. Propranolol and Oxytocin-Induced Contractility in Gravid Human Myometrium: An Ex Vivo Laboratory Study. BJOG. 2025 Aug;132(9):1228-1237. doi: 10.1111/1471-0528.18146. Epub 2025 Mar 24.

  PMID: 40129234 DERIVED

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Oxytocin; Propranolol

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; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Mrinalini Balki, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: September 8, 2017
• Primary Completion: August 19, 2022
• Study Completion: August 20, 2022
• Last Updated: February 24, 2023

Record last verified: 2023-02

Locations

CA (1)