Clinical trial NCT03957083: Oxytocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2
Official title: Oxytocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postpartum Hemorrhage
Obesity
Keywords: pregnancy
postpartum hemorrhage
Cesarean delivery
oxytocin
obesity
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2019-05-21
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Biased coin up-and-down design.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Uterine tone 2 minutes: questionnaire
timeFrame: 2 minutes
Secondary outcomes:
measure: Need for uterine massage: questionnaire
timeFrame: 20 minute
measure: Intraoperative requirement for additional uterotonic medication
timeFrame: 1 hour
measure: Calculated estimate of blood loss
timeFrame: 24 hours
measure: Intravenous fluid administered during surgery
timeFrame: 2 hours
measure: Hypotension: systolic blood pressure less than 80% of baseline
timeFrame: 2 hours
measure: Tachycardia: heart rate greater than 130% of baseline
timeFrame: 2 hours
measure: Bradycardia: heart rate less than 70% of baseline
timeFrame: 2 hours
measure: Presence of ventricular tachycardia: ECG
timeFrame: 2 hours
measure: Presence of atrial fibrillation: ECG
timeFrame: 2 hours
measure: Presence of atrial flutter: ECG
timeFrame: 2 hours
measure: Presence of nausea: questionnaire
timeFrame: 2 hours
measure: Presence of vomiting: questionnaire
timeFrame: 2 hours
measure: Presence of chest pain: questionnaire
timeFrame: 2 hours
measure: Presence of shortness of breath: questionnaire
timeFrame: 2 hours
measure: Presence of headache: questionnaire
timeFrame: 2 hours
measure: Presence of flushing: questionnaire
timeFrame: 2 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Jose Carvalho, MD
role: PRINCIPAL_INVESTIGATOR
References: