Principles
Intention-to-treat analyses will be used. Principal analyses will concern the assessment of the main effects of interventions based on outcomes aggregated at the site level (i.e. unit of randomisation). Tests of interaction will assess whether results differ between pre-specified subgroups. Subsidiary analyses will be done using individual-level data with allowance for clustering of observations by site. Multiple testing will be taken into account when interpreting results other than the principal analyses. The trial will be reported according to CONSORT guidelines.