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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Complications; Cesarean Section, Anesthesia; Reaction

Intervention / Treatment
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* Drug: Carbetocin Short-infusion
* Drug: Carbetocin Bolus application


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 46 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |