Renal Safety of Everolimus in Addition to Cyclosporine Microemulsion in Cardiac Transplant Recipients.

Inclusion criteria

• Male or female cardiac transplant recipients, 18-70 years old, with established cardiac allograft vasculopathy or at risk to develop a cardiac allograft vasculopathy.
• Patients who are more than 12 months post-transplant and who are receiving a cyclosporine microemulsion-based immunosuppressive regimen with/without azathioprine /mycophenolate mofetil, with/without steroids.
• Patients need to have stable renal function with a calculated GFR exceeding 40 ml/min (Nankivell).
• Patients without a biopsy-proven acute rejection ≥ grade 2, within 12 months prior to study entry.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. Effective contraception must be used during the trial and for 4 weeks following discontinuation of the study medication, even where there has been a history of infertility.
• Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

Exclusion criteria

• Patients who are recipients of multiple solid organ transplants.
• Patients with a calculated GFR of less than 40 ml/min.
• Patients with a biopsy-proven acute rejection episode ≥ 2 within 12 months prior to study entry.
• Patients who had received any investigational drug within 4 weeks prior to study entry.
• Patients currently being treated with sirolimus or having a history of prior therapy or having a hypersensitivity to drug similar to everolimus.
• Patient with a platelet count of < 50,000/mm3 or with a white blood cell count of ≤ 2,500/mm3 or with a hemoglobin value < 10 g/dL.
• Presence of severe hypercholesterolemia (≥ 9.1 mmol/L) or hypertriglyceridemia (≥ 8.55 mmol/L).
• Patient with NYHA class IV heart failure, or with left ventricular ejection fraction <30%. Patients with life-threatening cardiac allograft vasculopathy and/or graft dysfunction (life expectancy 1 year).
• Patients with severe systemic infections.
• Patients who are known to have HBsAg or HCV positive hepatitis, or who are HIV positive. Serology results obtained within 6 months prior to study entry are acceptable. If results cannot be obtained prior to study entry, a sample must be retained for later analysis. This stored sample will be destroyed at the end of study.
• Patients with any past (within the last 5 years) or present malignancy other than non-melanotic skin cancer.
• Existence of a co-morbid condition likely to result in death prior to study completion
• Symptoms of significant mental illness, which in the opinion of the investigator may interfere with the patient's ability to comply with the protocol. History of drug or alcohol abuse within 1 year of baseline.
• Inability to cooperate or communicate with the investigator.
• Female patients of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, or who are unwilling to use effective means of contraception.