Comparative Efficacy of Carbetocin Monotherapy Versus Carbetocin With Supplemental Oxytocin Infusion in Maintaining Uterine Tone and Preventing Blood Loss in Elective Cesarean Delivery: A Randomized, Double-Blind, Non-Inferiority Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 332
- 试验地点
- 1
研究概览
简要总结
Background: Carbetocin is an established single-dose uterotonic agent for postpartum hemorrhage prophylaxis at elective cesarean delivery. Despite its proven efficacy, many clinicians routinely add a supplemental oxytocin infusion following carbetocin administration without evidence-based justification. Concurrent oxytocin receptor stimulation may be redundant, counterproductive through receptor desensitization, or incrementally beneficial - a mechanistic uncertainty that remains unresolved in the published literature.
Objectives: To determine whether carbetocin monotherapy (100 micrograms IV bolus plus placebo infusion) is non-inferior to carbetocin plus supplemental oxytocin infusion (10 IU over 4 hours) in preventing the need for additional uterotonic agents within 24 hours of elective cesarean delivery.
Study Design: Prospective, randomized, double-blind, placebo-controlled, non-inferiority trial with an integrated pilot phase. Phase 1 (Pilot, n=60) establishes local feasibility and event rate. Phase 2 (Full trial, n=332) provides the definitive non-inferiority analysis.
Participants: Women aged 18-45 years undergoing elective cesarean delivery under spinal anesthesia at Qassim University Medical City, singleton pregnancy at or beyond 37 weeks, ASA physical status II, preoperative hemoglobin 9 g/dL or more.
Interventions: Group C (Monotherapy): Carbetocin 100 micrograms IV bolus plus placebo saline infusion 500 mL over 4 hours. Group C+O (Combination): Carbetocin 100 micrograms IV bolus plus oxytocin 10 IU in 500 mL saline over 4 hours.
Primary Outcome: Proportion of patients requiring at least one additional uterotonic agent within 24 hours of delivery.
Secondary Outcomes: Quantitative intraoperative blood loss by gravimetric measurement; total 24-hour blood loss; actual blood loss by Gross formula; hemoglobin and hematocrit changes; uterine tone scores by verbal numerical rating scale (0-10) at 2, 5, and 10 minutes; incidence of postpartum hemorrhage; blood transfusion requirement; hemodynamic profiles; adverse effects.
Sample Size: 332 patients (166 per group), non-inferiority margin 10 percentage points, one-sided alpha 0.025, 80% power, estimated baseline event rate 10%, with 15% dropout allowance.
详细描述
PHARMACOLOGICAL RATIONALE:
Carbetocin exerts its uterotonic effect through sustained occupancy of myometrial oxytocin receptors (OTRs). Continuous stimulation of OTRs triggers homologous receptor desensitization, progressively reducing myometrial responsiveness. The addition of an oxytocin infusion following carbetocin raises three competing hypotheses: (1) incremental benefit from residual unoccupied receptors; (2) receptor counterproductivity through accelerated downregulation; or (3) pharmacological redundancy. No published RCT has resolved this uncertainty.
TRIAL DESIGN:
The trial uses a non-inferiority design because the combination regimen is already practiced without evidence. Demonstrating non-inferiority of monotherapy would provide the first evidence to safely simplify uterotonic regimens, reduce drug costs, nursing workload, and unnecessary receptor stimulation.
BLOOD LOSS MEASUREMENT:
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult women aged 18 to 45 years
- •Scheduled for elective non-emergency cesarean delivery
- •Spinal anesthesia planned and administered as the sole anesthetic technique
- •Singleton pregnancy at gestational age of 37 completed weeks or more
- •ASA physical status II
- •Preoperative hemoglobin of 9 g/dL or more
- •Able to provide written informed consent in Arabic or English
排除标准
- •Emergency or crash cesarean delivery
- •Placenta previa, placenta accreta spectrum disorder, or other abnormal placentation
- •Known uterine anomalies likely to impair contractility including fibroids greater than 5 cm, bicornuate or unicornuate uterus
- •Grand multiparity defined as 5 or more previous deliveries
- •Multiple gestation including twins or higher order
- •Polyhydramnios defined as amniotic fluid index greater than 24 cm
- •Prior oxytocin augmentation in current pregnancy for more than 6 hours
- •Known hypersensitivity to carbetocin, oxytocin, or any formulation excipient
- •Severe preeclampsia, eclampsia, or HELLP syndrome
- •Cardiovascular disease including arrhythmia, valvular disease, cardiomyopathy, or ischemic heart disease
- •Known coagulopathy or thrombocytopenia with platelets less than 100 x 10^9/L
- •Hepatic or renal impairment
- •Body mass index greater than 40 kg/m2 at time of delivery
- •Enrollment in another interventional clinical trial
研究者
Mohamed Ahmed Tolba
Consultant Anesthesiologist
Mansoura University