Study to Evaluate Effect of Everolimus in Progression of Graft Vascular Illness on Patients With Heart Transplant (EVEROSTAT)

• Percentage of subjects that present at least one major clinical event due to graft vascular illness during the first year of the study on both treatment arms. [ Time Frame: December 2010 ] [ Designated as safety issue: Yes ]
  

• Intra-coronary ultrasound, safety and adverse events, Nt-proBNP, left ventricular systolic function, coronary stenosis. [ Time Frame: December 2010 ] [ Designated as safety issue: Yes ]
  

This is a prospective, randomized, multicentre, open and controlled study, to evaluate the efficacy and safety of everolimus combined with cyclosporin for microemulsion and steroids according to medical judgement, opposite to the usual therapy which the patient already has received (typically: ciclosporin + azathioprine or mycophenolate mofetil + steroids according to the judgement of the doctor) for patients receiving a cardiac orthotopic transplant since at least 12 months. The patients will be randomized in a 2:1 proportion (everolimus:control), in order to make it possible for the majority of patients to receive the potentially active treatment in a lethal illness for which there is not efficient known treatment up to date.

The study duration will be 2 years of follow-up for each patient. At the end of this period, the patients will be offered the possibility to maintain the immunosuppressive treatment to which they have been assigned, and periodic revisions will be made each 3-6 months.

The two treatment groups are:

Group I - Everolimus twice a day v.o. + cyclosporin for microemulsion in reduced doses +/- steroids.

Group II - Cyclosporin for microemulsion + azathioprine or mycophenolate mofetil +/- steroids (the same administration schedule and medication which the patient received earlier).