Clinical trial NCT03434444: In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol
Official title: In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol - Potential Applications in Induction of Labour and Treatment of Postpartum Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postpartum Hemorrhage
Keywords: propranolol
oxytocin
uterine contraction
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2018-02-15
Enrollment: 57
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Motility index
timeFrame: 3 hours
Secondary outcomes:
measure: Amplitude of contraction
timeFrame: 3 hours
measure: Frequency of contraction
timeFrame: 3 hours
measure: Integrated area under response curve (AUC)
timeFrame: 3 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Mrinalini Balki, MD
role: PRINCIPAL_INVESTIGATOR
References: