In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol

Postpartum Hemorrhage Clinical Trial

Official title:

In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol - Potential Applications in Induction of Labour and Treatment of Postpartum Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03434444
• Other study ID #: 18-04
• Status: Completed
• Phase: N/A
• Start date: September 8, 2017
• Est. completion date: August 20, 2022

Study information

• Verified date: February 2023
• Source: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Myometrial samples will be used to investigate the effect of propranolol on uterine contractions when exposed to high and low doses of oxytocin (to simulate PPH treatment and labor induction respectively).

The tissue will also be frozen at the end of the experiment, and Western blotting will be used to investigate the effect of propranolol on the expression patterns and cellular distribution of the oxytocin receptor and beta-adrenergic receptor and their signaling pathways in desensitized myometrium.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 20, 2022
• Est. primary completion date: August 19, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 40 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Oxytocin
Oxytocin in solution, ranging from 10 -12M to 10 -5M
• Propranolol
Propranolol in solution, 10-6M

Locations

Country	Name	City	State
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	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	Amplitude of contraction	The maximum extent of uterine muscle contraction, measured in grams (g). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.	3 hours
Secondary	Frequency of contraction	The number of contractions in uterine muscle (myometrium) over 10 minutes, spontaneously and in response to an agonist.; The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.	3 hours
Secondary	Integrated area under response curve (AUC)		3 hours