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

4 giugno 2026 aggiornato da: Mohamed Ahmed Tolba, Mansoura University

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

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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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:

Intraoperative blood loss measured by gravimetric quantification: [Weight soaked materials minus Weight dry materials] divided by 1.05, plus suction canister volume, minus irrigation volume, minus amniotic fluid volume. Secondary measurement uses the Gross formula: ABL = EBV x (Hb preoperative minus Hb postoperative) divided by Hb preoperative, 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 predefined anchor definitions, by the blinded operating obstetrician via bimanual palpation at 2, 5, and 10 minutes following carbetocin bolus. Pre-study inter-rater calibration session with intraclass correlation coefficient target of 0.80 or more.

STANDARDIZED FLUID PROTOCOL:

All patients receive a standardized intravenous fluid protocol to eliminate hemodilution as a confounding variable: spinal coload Ringer's Lactate 500 mL; intraoperative maintenance 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 volume recorded as a statistical covariate.

STATISTICAL ANALYSIS:

Non-inferiority declared if the upper bound of the two-sided 95% confidence interval of the risk difference does not exceed +0.10. Both per-protocol and intention-to-treat analyses 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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

332

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Arabia Saudita
    • Al-Qassim Region
      • Buraidah, Al-Qassim Region, Arabia Saudita, 51452
        • Qassim University Medical City
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Omar Saleh Al Misnid, MD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Group C - Carbetocin Monotherapy
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.
Droga: Carbetocin
Carbetocin 100 micrograms (1 mL) IV bolus administered over 1 minute immediately after umbilical cord clamping. Identical administration in both arms.
Altri nomi:
  • Duratocina
  • Pabal
Droga: Placebo Saline Infusion
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.
Altri nomi:
  • Normal Saline Placebo
Sperimentale: Group C+O - Carbetocin Plus Oxytocin
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).
Droga: Carbetocin
Carbetocin 100 micrograms (1 mL) IV bolus administered over 1 minute immediately after umbilical cord clamping. Identical administration in both arms.
Altri nomi:
  • Duratocina
  • Pabal
Droga: Oxytocin
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.
Altri nomi:
  • Syntocinon

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Additional Uterotonic Requirement Within 24 Hours
Lasso di tempo: Within 24 hours of delivery
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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Intraoperative Blood Loss - Gravimetric Method
Lasso di tempo: Intraoperative - from cord clamping to skin closure
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.
Intraoperative - from cord clamping to skin closure
Total 24-Hour Blood Loss
Lasso di tempo: 0 to 24 hours after delivery
Cumulative blood loss combining gravimetric intraoperative measurement and weighed postoperative lochia pads at 2 and 24 hours.
0 to 24 hours after delivery
Actual Blood Loss - Gross Formula
Lasso di tempo: Preoperative baseline to 24 hours postoperatively
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.
Preoperative baseline to 24 hours postoperatively
Hemoglobin Change
Lasso di tempo: Preoperative baseline to 24 hours postoperatively
Change in venous hemoglobin concentration from preoperative baseline to 24 hours postoperatively, measured by automated complete blood count analyzer.
Preoperative baseline to 24 hours postoperatively
Hematocrit Change
Lasso di tempo: Preoperative baseline to 24 hours postoperatively
Change in hematocrit from preoperative baseline to 24 hours postoperatively, measured by automated complete blood count analyzer.
Preoperative baseline to 24 hours postoperatively
Uterine Tone Score - Verbal Numerical Rating Scale
Lasso di tempo: At 2, 5, and 10 minutes after carbetocin bolus
Uterine tone assessed by blinded obstetrician using 11-point Verbal Numerical Rating Scale (0 = completely atonic, 10 = maximally contracted) via bimanual palpation at three timepoints.
At 2, 5, and 10 minutes after carbetocin bolus
Postpartum Hemorrhage Incidence
Lasso di tempo: Within 24 hours of delivery
Proportion of patients with total blood loss of 1000 mL or more within 24 hours of delivery, measured by gravimetric quantification.
Within 24 hours of delivery
Blood Transfusion Requirement
Lasso di tempo: Within 24 hours of delivery
Proportion of patients receiving packed red blood cell transfusion and total units of packed red blood cells transfused.
Within 24 hours of delivery
Systolic Blood Pressure
Lasso di tempo: Every 2.5 minutes intraoperatively and every 15 minutes for 4 hours postoperatively
Systolic blood pressure measured by non-invasive blood pressure cuff monitoring intraoperatively and in the postanesthesia care unit.
Every 2.5 minutes intraoperatively and every 15 minutes for 4 hours postoperatively
Heart Rate
Lasso di tempo: Continuous intraoperatively and every 15 minutes for 4 hours postoperatively
Heart rate measured by continuous 5-lead electrocardiogram monitoring intraoperatively and in the postanesthesia care unit.
Continuous intraoperatively and every 15 minutes for 4 hours postoperatively
Adverse Effects Incidence
Lasso di tempo: Within 24 hours of delivery
Incidence and severity of drug-related adverse effects including nausea, vomiting, facial flushing, headache, chest tightness, tachycardia, hypotension, and oliguria, documented by standardized checklist.
Within 24 hours of delivery

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Mansoura University

Investigatori

  • Investigatore principale: Mohamed A Tolba, MD, Qassim University Medical City

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 agosto 2026

Completamento primario (Stimato)

1 aprile 2028

Completamento dello studio (Stimato)

1 agosto 2028

Date di iscrizione allo studio

Primo inviato

4 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

4 giugno 2026

Primo Inserito (Effettivo)

9 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

9 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

4 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CARBOXY-RCT-001
  • QU-IRB-26-23-4 (Altro identificatore: Qassim University Institutional Review Board)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

De-identified individual participant data for the primary and all secondary outcome measures will be made available upon reasonable request to the principal investigator following publication of the primary results manuscript. Requests will be reviewed and approved based on scientific merit and ethical appropriateness. Requestors will be required to sign a data access agreement.

Periodo di condivisione IPD

Beginning 6 months after publication of the primary results manuscript and available for 5 years thereafter

Criteri di accesso alla condivisione IPD

Researchers with a methodologically sound proposal directed to the corresponding author. A signed data access agreement is required.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF
  • CODICE_ANALITICO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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