Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Intraoperative requirement for additional uterotonic medication
研究概览
简要总结
Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and mortality. Carbetocin is a uterotonic with a superior pharmacokinetic profile to oxytocin. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are as effective in achieving adequate uterine tone at elective cesarean section compared to the current recommended dose of 100mcg. However, this study was limited to those women with a body mass index (BMI) of <40 kg/m2. Maternal obesity has been shown to increase the risks of hemorrhage secondary to uterine atony, therefore the investigators wish to perform a dose finding study to determine the ED90 of carbetocin at caesarean section in those women with a BMI>40.
详细描述
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. Carbetocin is a synthetic oxytocin analogue. It causes uterine contraction via the same mechanism as oxytocin. Its duration of action is 4 to 7 times that of oxytocin due to an increased biological half-life in plasma and at the oxytocin receptors in the uterus. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of carbetocin at elective cesarean delivery to promote uterine contraction. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. However this study was limited to those women with a BMI of <40 kg/m2
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 carbetocin at caesarean section in those women with a BMI>40.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Refusal to give written informed consent
- •Allergy or hypersensitivity to carbetocin or oxytocin
- •Conditions (other than high BMI) that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.
- •Hepatic, renal, and vascular disease
- •Use of general anesthesia prior to the administration of the study drug
研究组 & 干预措施
Carbetocin 10mcg
Patient is given 10 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.
干预措施: Carbetocin (Drug)
Carbetocin 20mcg
Patient is given 20 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.
干预措施: Carbetocin (Drug)
Carbetocin 40mcg
Patient is given 40 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.
干预措施: Carbetocin (Drug)
Carbetocin 60mcg
Patient is given 60 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.
干预措施: Carbetocin (Drug)
Carbetocin 80mcg
Patient is given 80 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.
干预措施: Carbetocin (Drug)
Carbetocin 100mcg
Patient is given 100 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.
干预措施: Carbetocin (Drug)
结局指标
主要结局
Intraoperative requirement for additional uterotonic medication
时间窗: 1 hour
A request made by the obstetrician performing the cesarean delivery for additional uterotonic medication, due to bleeding or poor uterine tone.
次要结局
- Tachycardia: heart rate greater than 130% of baseline(2 hours)
- Estimated blood loss(24 hours)
- Intravenous fluid administered during surgery(2 hours)
- Hypotension: systolic blood pressure less than 80% of baseline(2 hours)
- Uterine tone 2 minutes(2 minutes)
- Uterine tone 5 minutes(5 minutes)
- Additional uterotonics administered(45 minutes)
- Bradycardia: heart rate less than 70% of baseline(2 hours)
- Presence of ventricular tachycardia: ECG(2 hours)
- Presence of atrial fibrillation: ECG(2 hours)
- Presence of atrial flutter: ECG(2 hours)
- Presence of nausea: questionnaire(2 hours)
- Presence of vomiting: questionnaire(2 hours)
- Presence of chest pain: questionnaire(2 hours)
- Presence of shortness of breath: questionnaire(2 hours)
- Presence of headache: questionnaire(2 hours)
- Presence of flushing: questionnaire(2 hours)