Lapaire 2006

Methods	2‐arm active‐controlled double‐blinded randomised trial.
Participants	Between January 1999 and February 2002, 56 parturients were randomised in a hospital setting in Switzerland. The population comprised women of unspecified parity, either singleton or multiple pregnancy, at high risk for PPH, who delivered by elective caesarean section. Exclusion criteria comprised parturients undergoing emergency caesarean section, or those with fetal distress, fetal malformations, pre‐eclampsia, HELLP syndrome, coagulopathy, severe systemic disorders, an American Society of Anaesthesiologists physical status of 3 or greater, severe asthma, previous myomectomy, pyrexia (more than 38.5°C) or hypersensitivity to prostaglandins.
Interventions	25 IU of oxytocin administered by an intravenous bolus plus infusion (n = 28) versus 800 mcg plus 5 IU of misoprostol plus oxytocin administered orally plus by an intravenous bolus (n = 28).
Outcomes	The study recorded the following outcomes: PPH at 500, PPH at 1000, additional uterotonics, transfusion, death, blood loss (mL), nausea, headache, shivering.
Notes	Contact with study authors for additional information: yes. Additional data from authors: yes.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The hospital pharmacy performed the 1:1 computer‐generated randomisation that assigned the participants to their group.
Allocation concealment (selection bias)	Low risk	Investigators used identical study boxes from pharmacy.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The study was "double‐blind": "the study drugs and placebos [were provided by the pharmacy] in unidentifiable form."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors were blinded to treatment allocations.
Objective assessment of blood loss	Low risk	When the membranes ruptured before delivery, investigators evaluated intraoperative and postoperative blood loss by determining the difference in weight of cloths and pads used to absorb blood during surgery and in the intermediate care unit. When membranes did not rupture preoperatively, investigators evaluated blood loss by collection in suction bottles and subtracting estimated amniotic fluid volume. Investigators considered that 1 g is equivalent to 1 mL of blood or amniotic fluid.
Incomplete outcome data (attrition bias) All outcomes	Low risk	"3 patients in the oxytocin group were excluded from statistical analysis because of errors in drug administration." Moreover calculated blood loss data were unavailable in 13 cases and for these women the primary outcome was estimated clinically.
Selective reporting (reporting bias)	High risk	The study protocol that was registered retrospectively (ClinicalTrials.gov) lists PPH as the primary outcome of the study, but the study report lists the primary outcomes as intraoperative and postoperative blood loss and drug‐related adverse effects (these items are listed only as secondary outcomes in the registration file). The study does not report the incidence of PPH at 500 mL, nor PPH at 1000 mL.
Intention to treat analysis	High risk	The authors excluded 3 study participants in the oxytocin group from the analysis because they incurred errors in drug administration.
Funding source	Low risk	The study was supported by funding from the Scientific Pool of Basel University Hospital (the institution of the authors).