E2. Interim Analyses The investigators anticipate two interim analyses after 50% and 75% of the sample size are recruited, but the exact timing will be at the discretion of the DSMB. Analyses will be performed by the study statistician and presented to the DSMB, which will make recommendations regarding further conduct of the trial. At their first meeting, the DSMB will establish thresholds and rules for trial stoppage based on safety and efficacy limits. Although early stopping decisions cannot be based purely on a mathematical stopping rule, the Haybittle-Peto stopping rule will be used as a guide. Under this rule, the interim analyses of the primary outcome would have to demonstrate an extreme difference between groups (p <0.001) to justify premature disclosure. This rule has the advantages that the exact number and timing of interim analyses need not be specified in advance and the overall type I error is preserved at 0.05. Therefore, samples size adjustments are not needed.