Oxytocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2

Sponsor

Samuel Lunenfeld Research Institute, Mount Sinai Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03957083

Collaborator

(none)

Enrollment

Location

Arms

7.3

Actual Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and mortality. Uterotonic drugs are used to improve the muscle tone of the uterus after birth, and these are effective at reducing the incidence of PPH. Oxytocin is the most commonly used uterotonic drug to prevent and treat PPH. Large doses of this drug are asociated with adverse effects like low blood pressure, nausea, vomiting, abnormal heart rhythms and changes on ECG. Various international bodies recommend varying and high doses of oxytocin in elective cesarean sections. A study performed at Mount Sinai Hospital showed that a much smaller dose of oxytocin is required (ED95 being 0.35IU). However, most of the women included in this study were below a body mass index (BMI) of 40kg/m2.

The investigators seek to find the best dose for patients with a BMI>40kg/m2, as a higher dose may be needed in this population to contract the uterus adequately.

Condition or Disease	Intervention/Treatment	Phase
Postpartum Hemorrhage Obesity	Drug: Oxytocin	N/A

Detailed Description

Postpartum hemorrhage (PPH) is one of the leading causes of death during childbirth and accounts for an estimated 140,000 deaths per year worldwide. The World Health Organization (WHO) recommends active management of the third stage of labor to prevent PPH, even in low risk patients. Prophylactic uterotonic drugs administered after delivery are the main element of active management of the third stage and have been demonstrated to reduce the incidence of PPH by up to 40%. Oxytocin is the most commonly used uterotonic in North America, however it has a very short duration of action and requires a continuous infusion to achieve sustained effect, with large doses associated with adverse effects like low blood pressure, nausea, vomiting, abnormal heart rhythms and changes on ECG.

The prevalence of obesity is increasing in young women and some studies have shown that obese women have higher rates of caesarean delivery compared to non-obese women. Other studies have demonstrated an increased risk of hemorrhage due to poor uterine tone in obese women. Laboratory studies show that BMI alone appears to contribute to blunted uterine muscle responses and therefore contraction responses to oxytocin in obese women.

Previous dose finding studies have excluded those women with a BMI of ≥40kgm2. Therefore, the investigators wish to perform a double-blind dose finding study using the biased coin up-and-down sequential allocation technique to determine the ED90 of oxytocin at cesarean section in those women with a BMI>40.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Biased coin up-and-down design.Biased coin up-and-down design.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Oxytocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2

Actual Study Start Date :

Jun 26, 2019

Actual Primary Completion Date :

Feb 3, 2020

Actual Study Completion Date :

Feb 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oxytocin 0.5IU Patient is given 0.5IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin Oxytocin administered intravenously, over 1 minute following delivery of the fetal head Other Names: pitocin
Active Comparator: Oxytocin 1IU Patient is given 1IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin Oxytocin administered intravenously, over 1 minute following delivery of the fetal head Other Names: pitocin
Active Comparator: Oxytocin 2IU Patient is given 2IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin Oxytocin administered intravenously, over 1 minute following delivery of the fetal head Other Names: pitocin
Active Comparator: Oxytocin 3IU Patient is given 3IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin Oxytocin administered intravenously, over 1 minute following delivery of the fetal head Other Names: pitocin
Active Comparator: Oxytocin 4IU Patient is given 4IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin Oxytocin administered intravenously, over 1 minute following delivery of the fetal head Other Names: pitocin
Active Comparator: Oxytocin 5IU Patient is given 5IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin Oxytocin administered intravenously, over 1 minute following delivery of the fetal head Other Names: pitocin

Outcome Measures

Primary Outcome Measures

Uterine tone 2 minutes: questionnaire [2 minutes]
Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 2 minutes after completion of the oxytocin injection.

Secondary Outcome Measures

Need for uterine massage: questionnaire [20 minute]
The obstetricians will be asked if there was any need for uterine massage beyond the initial 3 minute evaluation period following delivery.
Intraoperative requirement for additional uterotonic medication [1 hour]
A request made by the obstetrician performing the cesarean delivery for additional uterotonic medication, due to bleeding or poor uterine tone.
Calculated estimate of blood loss [24 hours]
Blood loss will be calculated through the difference in hematocrit values assessed prior to and at the end of 48 hours after the cesarean delivery, according to the following formula: Calculated blood loss = EBV ((Pre-op Htc-Post-op Htc)/pre-op Htc). EBV (estimated blood volume) in ml: patient's weight in kg x 85
Intravenous fluid administered during surgery [2 hours]
The total volume (ml) of fluid administered from entering the operating room to skin closure.
Hypotension: systolic blood pressure less than 80% of baseline [2 hours]
Systolic blood pressure < 80% of baseline, from drug administration until end of surgery
Tachycardia: heart rate greater than 130% of baseline [2 hours]
Heart rate > 130% of baseline, from drug administration until end of surgery
Bradycardia: heart rate less than 70% of baseline [2 hours]
Heart rate < 70% of baseline or a heart rate < 50bpm, from drug administration until end of surgery
Presence of ventricular tachycardia: ECG [2 hours]
Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery
Presence of atrial fibrillation: ECG [2 hours]
Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery
Presence of atrial flutter: ECG [2 hours]
Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery
Presence of nausea: questionnaire [2 hours]
The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient
Presence of vomiting: questionnaire [2 hours]
The presence of vomiting and number of episodes, from drug administration until end of surgery
Presence of chest pain: questionnaire [2 hours]
Any presence of chest pain, from drug administration until end of surgery, as reported by the patient
Presence of shortness of breath: questionnaire [2 hours]
Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient
Presence of headache: questionnaire [2 hours]
Any presence of headache, from drug administration until end of surgery, as reported by the patient
Presence of flushing: questionnaire [2 hours]
Any presence of flushing, from drug administration until end of surgery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

BMI ≥40kg/m2
Elective cesarean delivery under regional anesthesia
Gestational age ≥ 37 weeks
No known additional risk factors for postpartum hemorrhage
Written informed consent to participate in this study

Exclusion Criteria:

Refusal to give written informed consent
Allergy or hypersensitivity to oxytocin
Conditions (other than high BMI) that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, severe preeclampsia (as defined by SOGC guidelines (21)), eclampsia, polyhydramnios, uterine fibroids, previous history of uterine atony resulting in PPH, or bleeding diathesis.
Hepatic, renal, and vascular disease
Use of general anesthesia prior to the administration of the study drug