All adverse events, serious and non-serious were prospectively evaluated and recorded. Data safety was regularly reviewed by medical personnel of the CRO without any contact with investigators or patients on an ongoing basis according to the qualification of major events (death, readmission) and other adverse events. Since allocation of patients to the study drug or placebo was concealed, adjudication of adverse events and secondary efficacy end-points(including death and hospitalizations) was undertaken by each local principal investigator at each recruiting center.