Carbetocin Trial: Carbetocin Appropriate Rate Better Equilibrium Between Tonus (TOnus) and CIrculatioN (CARBETOCIN)

Double-blind Randomised Non-inferiority Trial to Assess Efficacy and Safety of Carbetocin After Caesarean Section Applied as Iv-bolus as Compared to a Short-infusion

Postpartum haemorrhage (PPH) is an obstetric emergency and defined as a blood loss of ≥500ml after vaginal birth and ≥1000ml after caesarean section (CS) and/or the need for blood transfusion within 24 hours after delivery (World Health Organization, Recommendations for the Prevention of Postpartum Haemorrhage. 2007; Leduc et al., J Obstet Gynaecol Can, 2009). Since PPH is more common after caesarean deliveries than after vaginal births and the rate of CS is rising over time and will probably continue to rise, the incidence of PPH is expected to increase accordingly.

A meta-analysis has shown that routine administration of an oxytocic agent after caesarean delivery leads to a reduced blood loss and decreases the risk of PPH (Cotter et al., Cochrane Database Syst Rev, 2001). The two most commonly used oxytocic drugs after operative delivery are oxytocin and carbetocin, a synthetic oxytocin-analogue. Carbetocin has the advantage over oxytocin of having a longer half-life and therefore reducing the use of additional uterotonics. Based on the findings of reduced cardiovascular side-effects with a short-infusion as compared to a bolus injection found for oxytocin (Thomas et al., Br J Anaesth, 2007), our study hypothesis is that a slower administration rate of carbetocin minimises the cardiovascular side effects without compromising the uterine tone. Therefore, we aim to investigate a short infusion of carbetocin 100 mcg applied in 100ml sodium chlorid compared to a bolus application in women undergoing primary or secondary caesarean delivery. This prospective, double-blind, randomised controlled non-inferiority trial will take place at the University Hospital Basel, Switzerland. We hypothesize uterine contraction not to be inferior (primary efficacy endpoint) and the mean arterial pressure to be higher after a short-infusion than after a bolus administration (primary safety endpoint).

Study Overview

• Status: Completed
• Conditions: Anesthesia; Reaction; Complications; Cesarean Section
• Intervention / Treatment: Drug: Carbetocin Short-infusion; Drug: Carbetocin Bolus application

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• healthy women
• singleton pregnancy
• caesarean section under regional anaesthesia
• older than 18 years
• written informed consent

Exclusion Criteria:

• emergency caesarean section
• secondary caesarean section due to fetal distress
• comorbidities (cardiovascular, kidney or liver disorder, epilepsy)
• obstetric diseases (hypertension, (pre-)eclampsia)
• uterine malformation (including uterine fibroids)
• bleeding disorder
• known hypersensitivity to carbetocin or oxytocin
• fetal malformation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short infusion; Carbetocin 100 microgram will be applied intravenously in a short infusion over about a minute	Drug: Carbetocin Short-infusion; Short-infusion of Carbetocin 100 microgram as compared to bolus application of Carbetocin 100 microgram (double dummy method)
Other: Bolus application; Carbetocin 100 microgram will be applied intravenously by bolus application over about 15 seconds	Drug: Carbetocin Bolus application; Carbetocin 100 microgram given intravenously as a bolus application over about 15 seconds

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal uterine tone	Uterine tone is assessed by the obstetrician on a linear analogue scale from 0 to 100	within the first 5 minutes after cord clamping

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure	mean arterial pressure is measured by a non-invasive blood pressure cuff at the upper arm	within first five minutes after cord clamping

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Obstetric Anaesthetists' Association United Kingdom
• Investigators: Principal Investigator: Salome Dell-Kuster, MD, Department of Anaesthesiology, University Hospital Basel, Switzerland

Publications and helpful links

General Publications

• Dell-Kuster S, Hoesli I, Lapaire O, Seeberger E, Steiner LA, Bucher HC, Girard T. Efficacy and safety of carbetocin given as an intravenous bolus compared with short infusion for Caesarean section - double-blind, double-dummy, randomized controlled non-inferiority trial. Br J Anaesth. 2017 May 1;118(5):772-780. doi: 10.1093/bja/aex034.
• Dell-Kuster S, Hoesli I, Lapaire O, Seeberger E, Steiner LA, Bucher HC, Girard T. Efficacy and safety of carbetocin applied as an intravenous bolus compared to as a short-infusion for caesarean section: study protocol for a randomised controlled trial. Trials. 2016 Mar 22;17:155. doi: 10.1186/s13063-016-1285-5.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 8, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin; Carbetocin
• Other Study ID Numbers: 2014-088