title: 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.
abstract: BACKGROUND
  The two most commonly used uterotonic drugs in caesarean section are oxytocin and carbetocin, a synthetic oxytocin analogue. Carbetocin has a longer half-life when compared to oxytocin, resulting in a reduced use of additional uterotonics. Oxytocin is known to cause fewer cardiovascular side effects when administered as a short-infusion compared to as an intravenous bolus. Based on these findings, we aim at comparing carbetocin 100 mcg given as a slow intravenous bolus with carbetocin 100 mcg applied as a short-infusion in 100 ml 0.9 % sodium chloride in women undergoing a planned or unplanned caesarean delivery. We hypothesise uterine contraction not to be inferior to a bolus application (primary efficacy endpoint) and greater haemodynamic stability to be achieved after a short-infusion than after a bolus administration, as measured by heart rate and mean arterial blood pressure (primary safety endpoint).
  
  
  METHODS
  This is a prospective, double-blind, randomised controlled, investigator-initiated, non-inferiority trial taking place at the University Hospital Basel, Switzerland. Uterine tone is quantified by manual palpation by the obstetrician using a linear analogue scale from 0 to 100 at 2, 3, 5 and 10 minutes after cord clamping. We will evaluate whether the lower limit of the confidence interval for the difference of the maximal uterine tone within the first 5 minutes after cord clamping between both groups does not include the pre-specified non-inferiority limit of -10. Both haemodynamic secondary endpoints will be analysed using a linear regression model, adjusting for the baseline value and the dosage of vasoactive drug given between cord clamping and 1 minute thereafter, in order to investigate superiority of a short-infusion as compared to a bolus application. We will follow the extension of CONSORT guidelines for reporting the results of non-inferiority trials.
  
  
  CONCLUSIONS
  Haemodynamic stability and adequate uterine tone are important outcomes in caesarean sections. The results of this trial may be used to optimise these factors and thereby increase patient safety due to a reduction in cardiovascular side effects.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT02221531 on 19 August 2014 and www.kofam.ch SNCTP000001197 on 15 November 2014.
authors.affiliation: Department of Anaesthesiology, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, 4031, Basel, Switzerland. salome.dell-kuster@usb.ch.|Basel Institute for Clinical Epidemiology and Biostatistics, Basel, Switzerland. salome.dell-kuster@usb.ch.
authors.forename: Salome
authors.initials: S
authors.lastname: Dell-Kuster
authors.affiliation: Department of Obstetrics and Antenatal Care, University Hospital Basel, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Hoesli
authors.affiliation: Department of Obstetrics and Antenatal Care, University Hospital Basel, Basel, Switzerland.
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.affiliation: Department of Anaesthesiology, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, 4031, Basel, Switzerland.
authors.forename: Esther
authors.initials: E
authors.lastname: Seeberger
authors.affiliation: Department of Anaesthesiology, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, 4031, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Luzius A
authors.initials: LA
authors.lastname: Steiner
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.affiliation: Department of Anaesthesiology, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, 4031, Basel, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Girard
mesh_terms: D002585:Cesarean Section / Q000009:adverse effects / Q000379:methods*; D002985:Clinical Protocols; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects; D010121:Oxytocin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011247:Pregnancy; D011446:Prospective Studies; D012107:Research Design; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D010120:Oxytocics; D010121:Oxytocin; C020731:carbetocin
keywords: Caesarean section; Carbetocin; Haemodynamic stability; Mode of administration; Uterine tone