Recovery of Oxytocin Responsiveness in Pregnant Human Myometrial Explants After Oxytocin-Induced Desensitization

NCT02051231 | Completed

• 1 other identifier: 14-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide and is caused most commonly by poor uterine muscle tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin, which acts by binding with oxytocin receptors (OTR) found on myometrial cells to cause uterine contraction. Women who require augmentation of labour with oxytocin because of inadequate labour progression are at increased risk of PPH because they have received intravenous oxytocin which exposes the uterus (and OTR) to doses greater than would normally be found without medical intervention. This exposure results in OTR desensitization and decreased uterine sensitivity to oxytocin which may lead to the use of much higher doses of oxytocin (up to 9x) or other agents for preventing and treating PPH with the potential for causing serious drug-related morbidity or fatality to the mother. Currently, in women who have failed labour augmentation and need to have a Cesarean delivery, it is not known if it would be beneficial to wait a certain period of time after discontinuing intravenous oxytocin before proceeding with the operation. The goal of the waiting time would be to allow the OTRs to recover and resensitize the uterus to the effects of oxytocin to avoid the need for high doses or additional uterus-contracting agents. Our hypothesis is that there will be a positive correlation between the magnitude of recovery of the myometrium's response to oxytocin and the time elapsed from the desensitizing oxytocin pretreatment (simulated labour augmentation).

Conditions

Postpartum Hemorrhage

Keywords

Uterine contraction; Oxytocin receptors; Oxytocin desensitization

Outcome Measures

Primary Outcomes (1)

• Amplitude of contraction

  2-4 hours

Secondary Outcomes (3)

• frequency of contraction

  2-4 hours

• Integrated area under response curve (AUC)

  2-4 hours

• basal tone

  2-4 hours

Study Arms (2)

Control

NO INTERVENTION

A control sample from each patient (no oxytocin applied) will be measured concurrently with samples treated with oxytocin.

Oxytocin

EXPERIMENTAL

Samples from each patient will be exposed to oxytocin and then allowed to rest for 30, 60 or 90 minutes.

Drug: Oxytocin

Interventions

Oxytocin DRUG

Oxytocin, 10-10mol/L to 10-5mol/L

Also known as: Pitocin

Oxytocin

Eligibility Criteria

• Age: 18 Years - 55 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 primary Cesarean section or first repeat Cesarean section

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 section
• Patients with a multiple pregnancy (more than one fetus)
• 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 with bleeding disorders

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Oxytocin

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

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: January 29, 2014
• First Posted: January 31, 2014
• Study Start: December 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: May 27, 2015

Record last verified: 2015-05

Locations

CA (1)