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

NCT07636421 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: CARBOXY-RCT-001QU-IRB-26-23-4
• Study Type: interventional
• Target: 332
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postpartum Hemorrhage; Cesarean Section; Blood Loss, Surgical; Uterine Atony

Keywords

Carbetocin; Oxytocin; Uterotonic; Elective Cesarean Delivery; Non-Inferiority Trial; Uterine Tone; Gravimetric Blood Loss; Obstetric Anesthesia; Spinal Anesthesia

Outcome Measures

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.

  Within 24 hours of delivery

Secondary Outcomes (11)

• Intraoperative Blood Loss - Gravimetric Method

  Intraoperative - from cord clamping to skin closure

• Total 24-Hour Blood Loss

  0 to 24 hours after delivery

• Actual Blood Loss - Gross Formula

  Preoperative baseline to 24 hours postoperatively

• Hemoglobin Change

  Preoperative baseline to 24 hours postoperatively

• Hematocrit Change

  Preoperative baseline to 24 hours postoperatively

Study Arms (2)

Group C - Carbetocin Monotherapy

ACTIVE COMPARATOR

Carbetocin 100 micrograms IV bolus over 1 minute immediately after cord clamping, followed by placebo infusion (500 mL 0.9% sodium chloride at 83 mL/hour over 4 hours). The infusion bag is visually identical to the active arm.

Drug: Carbetocin; Drug: Placebo Saline Infusion

Group C+O - Carbetocin Plus Oxytocin

EXPERIMENTAL

Carbetocin 100 micrograms IV bolus over 1 minute immediately after cord clamping, followed by active infusion (oxytocin 10 IU in 500 mL 0.9% sodium chloride at 83 mL/hour over 4 hours).

Drug: Carbetocin; Drug: Oxytocin

Interventions

Placebo Saline Infusion DRUG

500 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.

Also known as: Normal Saline Placebo

Group C - Carbetocin Monotherapy

Oxytocin DRUG

Oxytocin 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.

Also known as: Syntocinon

Group C+O - Carbetocin Plus Oxytocin

Carbetocin DRUG

Carbetocin 100 micrograms (1 mL) IV bolus administered over 1 minute immediately after umbilical cord clamping. Identical administration in both arms.

Also known as: Duratocin, Pabal

Group C - Carbetocin Monotherapy; Group C+O - Carbetocin Plus Oxytocin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mansoura University: lead

Study Sites (1)

Qassim University Medical City

Buraidah, Al-Qassim Region, 51452, Saudi Arabia

Location

MeSH Terms

Conditions

Postpartum Hemorrhage; Uterine Inertia; Blood Loss, Surgical

Interventions

carbetocin; Oxytocin

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Dystocia; Intraoperative Complications

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Mohamed A Tolba, MD

  Qassim University Medical City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamed A Tolba, MD

CONTACT

966507439018; m_atolba1234@mans.edu.eg

Omar S Al Misnid, MD9

CONTACT

966561205555; OMisnid@qumc.edu.sa

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Anesthesiologist

Model Details: Two parallel groups with 1:1 randomization. Group C receives carbetocin monotherapy (bolus plus placebo infusion). Group C+O receives carbetocin plus supplemental oxytocin infusion. Block randomization with variable block sizes of 4 and 6, stratified by parity.

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 9, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 6 months after publication of the primary results manuscript and available for 5 years thereafter
• Access Criteria: Researchers with a methodologically sound proposal directed to the corresponding author. A signed data access agreement is required.

Locations

SA (1)