The random allocation of patients to one of the two treatment groups was centrally managed by the coordinating centre, according to an automatically generated randomization list provided by the team responsible for the data collection monitoring and statistical analysis. An allocation ratio of 1:1 was assumed when generating the list. Patients eligible to enter the randomization procedure was sequentially assigned to the lowest randomization sequence number not yet assigned to any study subject. For each randomization number, a sealed envelope containing the randomization code was prepared by the team that generated the randomization list. Unblinding was permitted only if strictly necessary. In case it was essential to know the treatment assigned to a patient due to serious unexpected adverse events, the envelope containing the patient's randomization code could be open. In such cases, a detailed report on the timing, the causes and the patient's randomization number would have been issued by the person responsible for the trial and archived by the coordinating centre.