Hofmeyr 2004.

Methods	Next in a series of treatment packs containing 5 tablets of independently prepared, ordered in computer‐generated random sequence and numbered consecutively. Packs contained either placebo or misoprostol 5 × 200 mcg.
Participants	244 women with bleeding more than expected at least 10 minutes after delivery thought to be due to uterine atony and requiring additional uterotonic therapy.
Interventions	Routine active management of the third stage of labour with oxytocin 10 units or syntometrine 1 ampoule soon after birth. All participants were given all routine treatments for PPH (intravenous infusion, uterotonics, etc) from a special 'PPH Trolly'. Trial tablets (misoprostol 200 mcg or placebo) were administered: 1 orally, 2 sublingually and 2 rectally.
Outcomes	Primary outcomes: Measured blood loss 500 mL or more in first hour after enrolment Mean measured blood loss in first hour after enrolment Haemoglobin level day 1 after birth < 6 g/dL or blood transfusion Side effects (pyrexia 38.5 degrees Celsius or more, moderate or severe shivering 1 hour after enrolment) Secondary outcomes: Blood loss 1000 mL or more in first hour after enrolment Blood transfusion Haemoglobin level first day after birth < 8 g/dL or blood transfusion Additional uterotonic given after enrolment Manual removal of the placenta Evacuation of retained products of conception Hysterectomy Maternal death
Notes	6/244 data sheets did not have pack numbers completed and were excluded from the analysis. No abnormal outcomes were observed in any of the excluded group except 1 case of shivering and 1 of blood transfusion. No information given regarding allocation group. Authors were contacted to clarify amount of blood loss before recruitment, and they have provided the following information. The trial was planned as a PPH treatment trial to assess the effect of misoprostol over and above routine treatment of PPH. Entry criteria were intended to identify women who had PPH requiring additional treatment. No blood loss criterion was included, as clinically we diagnose PPH on the basis of ongoing abnormal bleeding, irrespective of the volume lost so far. Thus, all participants, in the opinion of the attending clinician, had abnormal bleeding requiring treatment. It is likely that, in most cases, this would have been more than 500 mL, but we do not have these data. 10 minutes was the minimum time after delivery, but in most cases, the time was longer (in the 3 cases of maternal mortality, enrolment ranged between 85 and 140 minutes after delivery).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	.Computer‐generated random sequence and numbered consecutively
Allocation concealment (selection bias)	Low risk	Adequate, as participants were allocated as next in a series of treatment packs containing 5 tablets of independently prepared trial drug (misoprostol or placebo).
Blinding (performance bias and detection bias) All outcomes	Low risk	Treatment sequence was kept sealed, and the code was broken only after complete entry and checking of all trial data.
Incomplete outcome data (attrition bias) All outcomes	Low risk	244 women were randomly assigned. Pack numbers for 6 women were incompletely filled in on the data sheets. Group allocation of these women was therefore unknown, and they could not be included in the analysis.
Selective reporting (reporting bias)	Unclear risk	No prior public registration of protocol.
Other bias	Unclear risk	Outcome measure of blood loss may have included blood and other liquids collected during delivery.