Rode 2011

Methods	Randomised, double‐blind, placebo‐controlled trial Multicentre, 17 centres in Denmark and Austria Between 1 June 2006 and 31 October 2008
Participants	677 women were randomised: 334 allocated to progesterone and 343 allocated to placebo Inclusion criteria: women with a live, diamniotic twin pregnancy and chorionicity assessed by ultrasound before 16 weeks’ gestation were eligible for recruitment Exclusion criteria: age < 18 years; known allergy to progesterone or peanuts (active treatment contained peanuts); history of hormone‐associated thromboembolic disorders; rupture of membranes; treatment for or signs of twin‐to‐twin transfusion syndrome; intentional fetal reduction; known major structural or chromosomal fetal abnormality; known or suspected malignancy in genitals or breasts; known liver disease; women with higher‐order multiple pregnancies; women who did not speak and understand Danish or German
Interventions	Intervention group: vaginal micronised progesterone pessaries (200 mg) ‐ self‐administered daily by participants ‐ starting from 20 ‐ 24 weeks until 34 weeks’ gestation Control/Comparison group: vaginal placebo pessaries (200 mg) ‐ self‐administered daily by participants ‐ starting from 20 ‐ 24 weeks until 34 weeks’ gestation
Outcomes	Primary outcome: incidence of delivery before 34 + 0 weeks' gestation Prespecified secondary outcomes: delivery before 22, 28 and 32 weeks' gestation, number of liveborn infants, treatment with tocolytics and corticosteroids, birthweight, selected neonatal complications, neurophysiological development 6 and 18 months after the estimated date of delivery
Notes	Funding sources: funding was provided by The Danish Medical Research Council, The Fetal Medicine Foundation, The Copenhagen University Hospital’s Research Fund, The Aase and Ejnar Danielsens Fund, The Augustinus Fund, The Ivan Nielsen Fund, The Doctor Sofus Carl Emil Friis and wife Olga Doris Friis’ Fund, The Simon Fougner Hartmanns Family Fund, The Danish Medical Society in Copenhagen and The A.P. Moeller Foundation Declarations of interest: the authors declare no conflict of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random‐number sequence was used by the trial statistician to generate a randomisation code
Allocation concealment (selection bias)	Low risk	The boxes of progesterone and placebo were packed and labelled by Bilcare (Waller House, Wales, UK) according to this randomisation sequence and shipped to Copenhagen University Hospital, from where the study medication was distributed to the participating departments. Each local researcher telephoned the randomisation system, entered the participant's social security number and chorionicity, and was given a randomisation number that corresponded to a specific treatment box from a given batch
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All participants and study personnel were blinded to treatment assignment for the duration of the trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The randomisation code was not broken before all data had been collected
Incomplete outcome data (attrition bias) All outcomes	Low risk	2 women of 675 lost to follow‐up
Selective reporting (reporting bias)	Low risk	Stated outcomes reported
Other bias	Unclear risk	Other bias not apparent