Interim analyses planned at 25%, 50%, and 75% of patients enrollment, with stopping rules for futility, safety, efficacy. Stopping rule for futility: relative risk for the primary outcome not inclusing the hypothesized value of 0.6 within 99% confidence interval at 50% interim analysis or 95% at 75% interim analysis. Stopping rule for efficacy in presence of a difference in favour of the GDP arm at a P value of 0.01 at 25% interim analysis or 0.05 at the 50% and 75% interim analyses. Stopping rule for safety in presence of a difference in favor of the control arm at a P value of 0.01 at the 25% interim analysis or 0.05 at the 50% and 75% interim analyses (Ethics Committe amendment August 2016).