Senat 2013

Methods	Open‐label multicentre, randomised controlled trial France ‐ 13 French University Hospitals Between June 2006 and January 2010
Participants	165 women randomised, 82 women randomised to the treatment group and 83 women randomised to the no‐treatment group Inclusion criteria: women older than 18 years, carrying twins, asymptomatic, and with a cervical length of 25 mm or less measured in the sagittal plane by routine transvaginal ultrasound according to the standard technique were eligible for inclusion. Women were 24+0 to 31+6 weeks' gestation Exclusion: cervical dilatation greater than 3 cm, premature rupture of the membranes, placenta previa, monochorial mono‐amniotic pregnancy, signs of twin‐to‐twin transfusion syndrome, severe intrauterine growth restriction of at least 1 fetus, known major structural or chromosomal fetal abnormality, death of 1 fetus, any maternal or fetal disease requiring preterm birth, progesterone therapy before inclusion, ongoing anticonvulsant treatment, or participation in any other treatment trial. Twin gestations resulting from intentional fetal reduction were also excluded
Interventions	Intervention group: 500 mg of intramuscular 17‐alpha‐hydroxyprogesterone caproate, to be repeated twice weekly until 36 weeks or preterm delivery, whichever occurred first Control group: no treatment
Outcomes	Primary outcome: time from randomisation to delivery Prespecified secondary outcomes: (1) obstetric criteria: rates of preterm birth before 37, 34, and 32 weeks and number of readmissions for preterm labour; (2) neonatal criteria: birthweight, transfer to the NICU, RDS, bronchopulmonary dysplasia, NEC, periventricular leukomalacia, and death; and (3) safety criteria: any severe maternal or neonatal adverse effects (congenital anomalies or other ill effects)
Notes	Funding sources: this study was supported by a research grant from the Département à la Recherche Clinique Ile‐de‐France, Assistance Publique–Hôpitaux de Paris, which also sponsored the study (PHRC AOM 04038) Declarations of interest: the authors declare no conflicts of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	An independent computer‐generated randomisation sequence was used for this allocation, based on a randomisation list established by the study statistician, according to a permutated block method
Allocation concealment (selection bias)	Low risk	States ‐ central randomisation. “A centralised, computer generated randomised process in a 1:1 ratio.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data available on all participants
Selective reporting (reporting bias)	Low risk	Stated outcomes reported
Other bias	Unclear risk	Other bias not apparent