Stopping rules and exclusion of study centers
ADVERSE EVENTS, RECRUITMENT
Participating centers will be discontinued if their recruitment rate is less than 50% of the agreed recruitment rate indicated in the declaration of commitment at mid-recruitment (15 months into the recruitment period), and either no efforts have been undertaken to improve recruitment rate, or all opportunities for improving recruitment rate have been exhausted. The Data Safety and Monitoring Board (DSMB) has the right to discontinue the trial prematurely, in case of at least one of the following situations: Severe adverse events, substantial changes in risk–benefit considerations, insufficient recruitment.