| Methods |
3‐arm active‐controlled triple‐dummy randomised trial |
| Participants |
270 women were randomised in a hospital setting in Egypt. The population comprised women of any parity, a singleton pregnancy, at high risk for PPH, who delivered by elective caesarean section. Exclusion criteria comprised women with hypersensitivity to oxytocin, carbetocin, or prostaglandins; contraindication to treatment with prostaglandins (e.g. glaucoma); history of significant heart disease; severe asthma; epilepsy; history or evidence of liver, renal, or vascular disease; history of coagulopathy, thrombocytopenia, or anticoagulant therapy; HELLP syndrome or eclampsia; placental abruption; or contraindication to spinal anaesthesia. |
| Interventions |
100 mcg of carbetocin administered by an IV bolus versus 400 mcg of misoprostol administered sublingually versus 30 IU of oxytocin administered by an IV bolus + infusion |
| Outcomes |
The study recorded the following outcomes: PPH at 500; PPH at 1000; additional uterotonics; transfusion; death; nausea; vomiting; headache; fever; shivering; abdominal pain. |
| Notes |
Contact with study authors for additional information: no. Additional data from authors: no |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Randomisation was performed in a 1:1:1 ratio using a computer‐generated sequence. |
| Allocation concealment (selection bias) |
Low risk |
Numbered, sealed envelopes were prepared, with each envelope containing 1 of the 3 study drugs and placebos for the other 2 drugs. The randomisation protocol was concealed from the research team and the primary investigator contacted a central co‐ordinating investigator to identify the envelope to be distributed to each patient. |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Tablet placebos, containing hydrogenated castor oil, hypromellose, microcrystalline cellulose, and sodium starch glycolate were prepared to be identical in size, colour, shape, and packing to the tablet study drug. Intravenous placebo ampoules containing normal saline were prepared and were identical in shape and packing to the IV study drugs used. All envelopes were prepared by Sigma Pharmaceuticals and were already sealed when received by the research team. |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Consequently, patients, investigators, and data analysts were masked to group assignments and unmasking only occurred after data analysis was completed. |
| Objective assessment of blood loss |
Low risk |
Surgical towels were weighed with their wrapping before and after delivery using a highly accurate digital balance. The difference in mass between the dry and soaked towels was calculated. Operative blood loss was calculated using 3 parameters: (A) the volume of the suction bottle contents (mL), (B) the difference in towel mass (g), and © the amniotic fluid volume (mL). Intraoperative blood loss (mL) was calculated as: Intraoperative blood loss = (A + B) −C. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
270 women were randomised in the study, but 7 were excluded because they had general anaesthesia (n = 4) or the drug ampoules were damaged after randomisation. |
| Selective reporting (reporting bias) |
Low risk |
The study report matches the study protocol that was registered (ClinicalTrials.gov: NCT02053922). |
| Intention to treat analysis |
High risk |
Those who were excluded from the study after randomisation were not included in the analysis. |
| Funding source |
Unclear risk |
Source(s) of funding for the study were not reported. |
