Carbetocin Monotherapy Versus Carbetocin Plus Oxytocin Infusion in Elective Cesarean Delivery: A Non-Inferiority Trial
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorMansoura University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Carbetocin
DrugCarbetocin 100 micrograms (1 mL) IV bolus administered over 1 minute immediately after umbilical cord clamping. Identical administration in both arms.
Oxytocin
DrugOxytocin 10 IU added to 500 mL 0.9% sodium chloride, infused at 83 mL/hour over 4 hours, initiated within 2 minutes of carbetocin bolus. Administered in the combination arm only.
Placebo Saline Infusion
Drug500 mL 0.9% sodium chloride infused at 83 mL/hour over 4 hours, initiated within 2 minutes of carbetocin bolus. Visually identical to the active oxytocin infusion. Administered in the monotherapy arm only.
Treatment groups
332 Participants
are divided into 2 treatment groupsGroup A: Group C - Carbetocin MonotherapyActive comparator 2 interventions
Group B: Group C+O - Carbetocin Plus OxytocinExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Additional Uterotonic Requirement Within 24 Hours
Proportion of patients requiring at least one additional rescue uterotonic agent at any timepoint within 24 hours of delivery, based on clinical assessment of inadequate uterine tone or uterine atony by the attending obstetrician or anesthesiologist.
Time frame
Within 24 hours of deliverySecondary outcomes
1
Intraoperative Blood Loss - Gravimetric Method
Quantitative intraoperative blood loss measured by gravimetric method: weight of soaked materials minus dry materials divided by 1.05, plus suction volume, minus irrigation and amniotic fluid volumes.
Time frame
Intraoperative - from cord clamping to skin closure2
Total 24-Hour Blood Loss
Cumulative blood loss combining gravimetric intraoperative measurement and weighed postoperative lochia pads at 2 and 24 hours.
Time frame
0 to 24 hours after delivery3
Actual Blood Loss - Gross Formula
Calculated using estimated blood volume multiplied by the ratio of preoperative to postoperative hemoglobin change: ABL = EBV x (Hb preoperative minus Hb postoperative) divided by Hb preoperative, where EBV = body weight in kg x 85 mL/kg.
Time frame
Preoperative baseline to 24 hours postoperatively4
Hemoglobin Change
Change in venous hemoglobin concentration from preoperative baseline to 24 hours postoperatively, measured by automated complete blood count analyzer.
Time frame
Preoperative baseline to 24 hours postoperativelySponsors and contacts
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Source ClinicalTrials.gov