Interim analysis
A group sequential design, with O’Brien–Fleming stopping rules (which preserved the 5% significance level in the final analysis), was used to allow the DMC to review the primary outcome for evidence of harm, benefit or futility. Two unadjusted interim analyses were performed—the first after 124 patients were randomized and reached 7 d after randomization and the second after 248 patients were randomized and reached 7 d after randomization. The stopping rules were used as a guideline, alongside the other safety data available to the DMC, as an overall assessment of the trial. The interim analyses were performed by the trial statistician who was unblinded to the treatment arm, and these results were presented to the DMC only. The DMC reported its recommendations, without disclosing any trial results, to the TSC, which made the final decision regarding continuation of the trial.