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NCT Number: NCT03434444

In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol

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.

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Key information

Conditions

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

Age range

16 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Oxytocin

Drug

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

Other names: pitocin

Propranolol

Drug

Propranolol in solution, 10-6M

Primary outcomes

  1. Motility index

    Time frame: 3 hours

    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.

Secondary outcomes

  1. Amplitude of contraction

    Time frame: 3 hours

    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.

  2. Frequency of contraction

    Time frame: 3 hours

    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. Integrated area under response curve (AUC)

    Time frame: 3 hours

Sponsors and collaborators

Lead sponsor

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2022
Study completion
2022
First posted
Feb 15, 2018
Registry last updated
Feb 24, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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