| Study characteristics |
| Methods |
2‐arm placebo‐controlled randomised trial |
| Participants |
4153 women were randomised in a hospital setting in the UK from May 2015 to June 2017. The population comprised women aged 16 to 39 years of age, if they had completed less than 12 weeks of pregnancy, if they presented with vaginal bleeding, and if they had an intrauterine gestational sac that was visible on ultrasonography. Exclusion criteria comprised women that if at the time of presentation the fetal crown–rump length was 7 mm or longer with no visible heartbeat; if the gestational sac was a mean of 25 mm or greater in diameter with no visible fetal pole on ultrasonography; if they had evidence of ectopic pregnancy; if they had life‐threatening bleeding; if they had current or recent use of progesterone supplementation; if they had contraindications to progesterone therapy (i.e. a history of liver tumours; current genital or breast cancer, severe arterial disease, or acute porphyria; or a history during pregnancy of idiopathic jaundice, severe pruritus, or pemphigoid gestationis); or if they were participating in any other blinded, placebo controlled trials of medicinal products in pregnancy. |
| Interventions |
Twice daily vaginal suppositories containing 400 mg of micronized progesterone versus placebo. |
| Outcomes |
The study recorded the following outcomes relevant for this review: live birth, miscarriage (< 24 weeks), preterm birth (< 37 weeks), stillbirth, ectopic pregnancy, congenital abnormalities and adverse drug events. |
| Notes |
Contact with study authors for additional information: no. Additional data from authors: no. Funded by the United Kingdom NIHR Health Technology Assessment program (project number HTA 12/167/26). The authors declare no relevant conflicts of interest. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Computer generated in 1:1 ratio with the use of minimization. |
| Allocation concealment (selection bias) |
Low risk |
Through a secure, centralised Internet facility. |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Study participants and caregivers were blinded to treatment allocations. |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Assessors were blinded to treatment allocations. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Attrition bias was < 10% and balanced across study arms. |
| Selective reporting (reporting bias) |
Low risk |
The study report matches the study protocol (ISRCTN14163439) that was registered prospectively. |
| Other bias |
Low risk |
Funded by the United Kingdom NIHR Health Technology Assessment programme (project number HTA 12/167/26). |
