Clinical trial NCT02221531: Carbetocin Trial: Carbetocin Appropriate Rate Better Equilibrium Between Tonus (TOnus) and CIrculatioN
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Complications; Cesarean Section
Anesthesia; Reaction
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Obstetric Anaesthetists' Association United Kingdom
First posted: 2014-08-20
Enrollment: 140
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Maximal uterine tone
timeFrame: within the first 5 minutes after cord clamping
Secondary outcomes:
measure: Mean arterial pressure
timeFrame: within first five minutes after cord clamping
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: Department of Anaesthesiology, University Hospital Basel, Switzerland
name: Salome Dell-Kuster, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.