Carbetocin vs. Oxytocin: In-vitro Myometrial Contractions With and Without Oxytocin Pre-treatment

The purpose of this study is to compare the ability of an isolated sample of uterine muscle tissue (in a tissue bath) to contract in the presence of various drugs. The drugs studied--uterotonics--are typically used to contract the uterus when a pregnant patient continues to bleed after delivery. Oxytocin is an old standard, but seems to suffer from a desensitization phenomenon. Carbetocin, a similar drug, has recently been suggested to clinicians as a replacement for oxytocin directly after certain types of Cesarean section.

The investigators will be testing isolated uterine muscle samples after pre-treatment with oxytocin OR nothing (control) to increasing concentrations of oxytocin OR carbetocin. Contractile measures will be measured and compared between all groups. The investigators hypothesize that oxytocin pre-treatment will reduce contractions in both oxytocin- and carbetocin-induced contractions, and oxytocin and carbetocin will induce different patterns of contractions.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Oxytocin; Drug: Carbetocin

Detailed Description

Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity. In 80% cases of PPH, the primary cause is failure of the uterus to contract after delivery of the baby, which then requires further treatment of the mother with uterotonic drugs (drugs used to contract uterus and thus prevent bleeding).

Patients participating in this study will be asked to donate a very small sample of uterine tissue during Cesarean section, which will be tested in the laboratory for the ability to contract in response to the uterotonics oxytocin and carbetocin. We will seek to better understand the effects of these drugs by comparing their contractile capability in isolated uterine tissue.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gestational age 37-41 weeks
• Non-laboring patients, not exposed to exogenous oxytocin
• Patients requiring primary or first repeat Cesarean section
• Cesarean section under spinal anesthesia

Exclusion Criteria:

• Patients who require general anesthesia
• Patient who had previous myometrial surgery or more than one previous Cesarean section
• Patients with placental anomalies
• Emergency Cesarean section in labor
• Patients with multiple pregnancy (twins, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No drug pre-treatment; A control sample from each patient (no uterotonic drug will be applied during pre-treatment) will be measured concurrently with samples pre-treated with oxytocin. Controls will undergo the same dose response of oxytocin or carbetocin after pre-treatment period as the groups given oxytocin for pre-treatment.	Drug: Oxytocin; Oxytocin, 10-10mol/L to 10-5mol/L; solution made in double-distilled autoclaved water and then tested in physiological salt solution.; Other Names: Pitocin; Drug: Carbetocin; Carbetocin, 10-10mol/L to 10-5mol/L; solution made in double-distilled autoclaved water and then tested in physiological salt solution.; Other Names: Duratocin
Active Comparator: Drug pre-treatment; A sample from each patient will be pre-treated with oxytocin 10-5mol/L. These samples will undergo the same dose response of oxytocin or carbetocin after pre-treatment period as the groups given no drug for pre-treatment (controls).	Drug: Oxytocin; Oxytocin, 10-10mol/L to 10-5mol/L; solution made in double-distilled autoclaved water and then tested in physiological salt solution.; Other Names: Pitocin; Drug: Carbetocin; Carbetocin, 10-10mol/L to 10-5mol/L; solution made in double-distilled autoclaved water and then tested in physiological salt solution.; Other Names: Duratocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Amplitude of contraction	6-8 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Integrated area under response curve (AUC)	6-8 hours
Basal tone	6-8 hours
Frequency of contraction	6-8 hours

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Collaborators: University of Toronto

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: September 17, 2012
• First Submitted That Met QC Criteria: September 17, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Estimate): September 21, 2012
• Last Update Submitted That Met QC Criteria: September 17, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Oxytocin; Uterine contraction; Dose response; Carbetocin; Oxytocin pretreatment
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin; Carbetocin
• Other Study ID Numbers: 12-05; 11-0257-E (Other Identifier: REB (MSH))