Coomarasamy 2015

Methods	Unit of randomization: pregnancy Method of randomization: computer‐generated Timing of randomization: before conception, reconfirmed after became pregnant Blinding: yes Power calculation: yes, needed 376 women in each group, planned to recruit 790 women to allow for loss to follow‐up Number of centers: multiple ‐ recurrent miscarriage clinics across the UK (36 sites) and Netherlands (9 sites) 836 women randomized, 826 women had results for primary outcome to analyze Source of funding: UK NIHR
Participants	Women with ≥ 3 unexplained miscarriages trying to actively conceive naturally. Exclusions: unable to conceive after 1 year of being in trial, recognized thrombophilic condition, uterine anomalies, abnormal parental karyotype, or other identifiable cause of recurrent miscarriage. Age: 18‐39 years Location: UK and Netherlands Timing and duration: June 2010‐October 2013
Interventions	400 mg micronized progesterone vaginal suppositories twice daily. Began therapy "soon after receiving a positive" urine pregnancy test (no later than 6 weeks of gestation) through 12 weeks of duration. Control: matched placebo
Outcomes	Live birth after 24 weeks (primary), clinical pregnancy, ongoing pregnancy with fetal heart activity at 12 weeks, miscarriage (loss < 24 weeks), gestational age at delivery, neonatal survival, congenital anomalies, exploratory outcomes ‐ pre‐eclampsia SGA, PPROM, hemorrhage, neonatal outcomes
Notes	PROMISE trial Dates of study: June 2010‐October 2013 Funding sources: UK NIHR Declarations of interest: disclosure forms on file at NEJM.org, not stated in paper
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomization
Allocation concealment (selection bias)	Low risk	Assignment through secure internet facility
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "participants, physicians, and trial nurses were unaware of the study‐group assignments throughout the trial" Comment: identical drug and placebo
Blinding of outcome assessment (detection bias) All outcomes	Low risk	As above
Incomplete outcome data (attrition bias) All outcomes	Low risk	10 total lost to follow‐up
Selective reporting (reporting bias)	Low risk	All outcomes reported on
Other bias	Low risk	No other biases identified