Withdrawal of Steroids, Cyclosporine A Dose Reduction and Switch to Mycophenolatmofetile After Heart Transplantation

• Cardiovascular risk factors at month 12 and month 24 [ Time Frame: month 12 and month 24 ] [ Designated as safety issue: No ]
• Acute rejection episodes, gastrointestinal disorders and other adverse events at month 12 and month 24 [ Time Frame: month 12 and month 24 ] [ Designated as safety issue: Yes ]
• Quality of life assessed by the SF36, spiroergometry, concomitant medication at month 12 and month 24 [ Time Frame: month 12 and month 24 ] [ Designated as safety issue: No ]

• cardiovascular risk factors at month 12 and month 24
• acute rejection episodes, gastrointestinal disorders and other adverse events at month 12 and month 24
• quality of life assessed by the SF36, spiroergometry, concomitant medication at month 12 and month 24

The purpose of this study is first to improve or save renal function and second to decrease cardiac risk factors by optimising the immunosuppressive regimen by withdrawing steroids and reducing the Cyclosporine A dose. The concomitant administration of Mycophenolatmofetile, an effective immunosuppressive agent, will minimize the risk of acute rejection episodes.

The decrease of quality of life in patients after heart transplantation in the long-term is determined by an increasing incidence of transplant vasculopathy and by immunosuppression-related side effects. Calcineurin inhibitors are associated with chronic nephrotoxicity, while long-term administration of steroids results in an increased incidence of cardiovascular risk factors (e.g. hypertension, lipometabolic disorders, steroid induced diabetes, adipositas)and therefore, carries the potential of graft disfunction.

• Drug: prednisolon
  prednisolon withdrawal: reduction of maintenance dosage, 0,5 mg of the daily dose every week till withdrawal
  Other Names:

  • Decortin
  • steroid withdrawal
• Drug: Mycophenolatmofetile
  Mycophenolatmofetile administration: start doses 250 mg, increase of the daily dose about 250 mg every week till reaching 2 g/daily
  Other Names:

  • MMF
  • Cellcept
• Drug: Cyclosporin A
  Cyclosporin A reduction: 8 weeks after starting prednisolon withdrawal and Mycophenolatmofetile administration reduction of Cyclosporin A trough level till a range from 50 to 90 ng/ml
  Other Name: Sandimmun optoral

Inclusion Criteria:

• Current immunosuppressive regimen: Cyclosporine A and corticosteroids for at least six month
• Heart transplantation above 3 years dated back
• Serum creatinine < 3,5 mg/dl (310 µmol/l) and BUN < 150 mg/dl
• Cyclosporine A blood level between 50 and 250 ng/ml during the last 12 month

Exclusion Criteria:

• Carcinoma within the last 3 years
• Acute rejection episodes during the last 6 month
• Infection requiring therapeutic intervention
• Hepatitis B, Hepatitis C or HIV infection
• WBC < 3000/µl, haemoglobin < 9g/dl, platelets < 70.000/µl
• Florid gastrointestinal ulcer
• Haemodialysis within the last 4 weeks before study entry
• Pregnancy / lactation
• Administration of other immunosuppressive agents than prescribed
• Mycophenolatmofetile incompatibility