CERTICOEUR: A Secondary Prevention Study of Skin Cancers in Heart Transplant Patients. Everolimus Versus Calcineurin Inhibitors Multicenter Trial

• Open labelled randomized Everolimus vs reduction of calcineurin inhibitors trial. 2:1 randomization design
• October 10, 2008
• 159 patients (106 everolimus vs 53 calcineurin inhibitors reduction)
• 175 patients (117 vs 58)
• X Not yet recruiting 0 recruiting 0 no longer recruiting
• Number of skin tumors per patients requiring surgery with histology control within 2 years

Within 2 years of Follow up:

• New skin cancer
• Number of patients with new skin cancers
• Time of recurrence
• Number and histology of other types of skin cancer
• Graft function (including acute rejection, graft loss, death)
• Renal function evolution as assessed using Cockcroft creatinine clearance and proteinuria
• Adverse events and serious adverse events
• Non skin cancer (Number and diagnostic)
• Schemes of calcineurin inhibitors reduction/withdrawal
• Immune response assessment through regulatory or effector function of blood and in situ T lymphocytes at baseline and following immunosuppression switch

Inclusion criteria

• First orthotopic heart transplant after 1st year
• No rejection within previous 6 Months
• Occurrence of squamous cell carcinoma, basal cell carcinoma, in situ carcinoma, Bowen disease, premalignant keratosis
• Recurrence of skin cancers leading to immunosuppressive regimen modifications
• Removal of a skin lesion in the past three years
• Above 18 yrs and under contraceptive drugs if applicable
• Informed consent given
• Health coverage ongoing

Exclusion criteria

• Other non simultaneously transplanted organ
• recent biopsy proven acute rejection
• Proteinuria > 1g/l
• Ongoing infectious disease
• HIV positivity, Chronic active Hepatitis B or C.
• Abnormal blood tests: transaminases >= 3UNL, Bilirubin > 34 mmol.l, albumin<35 g/l, spontaneous INR >1,3
• Hemoglobin >= 8 g/dl, White Blood Count<= 2 giga/l, platelet count <= 50 giga/l
• Hypercholesterolemia>= 9 mmol/l, hypertriglyceridemia >= 8,5 mmol/l despite treatment
• History of macrolid or mTor inhibitor intolerance
• Previous cancer other than skin in the year prior to enrollment
• Medical or surgical condition unsuitable for the trial
• Breast feeding
• Positive pregnancy test
• Severe psychiatric disorder
• Communication or language disability