Carbetocin Monotherapy Versus Carbetocin Plus Oxytocin Infusion in Elective Cesarean Delivery: A Non-Inferiority Trial

PHARMACOLOGICAL RATIONALE:Carbetocin exerts its uterotonic effect through sustained occupancy of myometrialoxytocin receptors (OTRs). Continuous stimulation of OTRs triggers homologous receptordesensitization, progressively reducing myometrial responsiveness. The addition of anoxytocin infusion following carbetocin raises three competing hypotheses: (1) incrementalbenefit from residual unoccupied receptors; (2) receptor counterproductivity throughaccelerated downregulation; or (3) pharmacological redundancy. No published RCT hasresolved this uncertainty.TRIAL DESIGN:The trial uses a non‐inferiority design because the combination regimen is alreadypracticed without evidence. Demonstrating non‐inferiority of monotherapy would providethe first evidence to safely simplify uterotonic regimens, reduce drug costs, nursingworkload, and unnecessary receptor stimulation.BLOOD LOSS MEASUREMENT:Intraoperative blood loss measured by gravimetric quantification: [Weight soakedmaterials minus Weight dry materials] divided by 1.05, plus suction canister volume,minus irrigation volume, minus amniotic fluid volume. Secondary measurement uses theGross formula: ABL = EBV x (Hb preoperative minus Hb postoperative) divided by Hbpreoperative, where EBV = body weight (kg) x 85 mL/kg.UTERINE TONE ASSESSMENT:Assessed using the 11‐point Verbal Numerical Rating Scale (VNRS 0‐10) with predefinedanchor definitions, by the blinded operating obstetrician via bimanual palpation at 2, 5,and 10 minutes following carbetocin bolus. Pre‐study inter‐rater calibration session withintraclass correlation coefficient target of 0.80 or more.STANDARDIZED FLUID PROTOCOL:All patients receive a standardized intravenous fluid protocol to eliminate hemodilutionas a confounding variable: spinal coload Ringer's Lactate 500 mL; intraoperativemaintenance 100 mL/hour; study infusion 500 mL over 4 hours identical in both groups;postoperative Ringer's Lactate 80 mL/hour for 8 hours. Total 24‐hour fluid volumerecorded as a statistical covariate.STATISTICAL ANALYSIS:Non‐inferiority declared if the upper bound of the two‐sided 95% confidence interval ofthe risk difference does not exceed +0.10. Both per‐protocol and intention‐to‐treatanalyses performed; concordance of both required per ICH E9(R1). IRB approval:Subcommittee of Health and Bioethics Research Ethics, Qassim University, Approval No.26‐23‐4, dated June 02, 2026.