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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Conversion Study to Optimize Immunosuppressive Regimen by Withdrawal of Steroids, Cyclosporine A Dose Reduction and a Switch to Mycophenolatmofetile for Patients After Heart Transplantation in the Long-Term.

Conditions
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Heart Transplantation

Intervention / Treatment
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* Drug: prednisolon
* Drug: Mycophenolatmofetile
* Drug: Cyclosporin A


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>prednisolon withdrawal: reduction of maintenance dosage, 0,5 mg of the daily dose every week till withdrawal; Mycophenolatmofetile administration: start doses 250 mg, increase of the daily dose about 250 mg every week till reaching 2 g/daily; 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 mg/ml | Drug: prednisolon<br>* prednisolon withdrawal: reduction of maintenance dosage, 0,5 mg of the daily dose every week till withdrawal<br>* Other names: steroid withdrawal;Drug: Mycophenolatmofetile<br>* Mycophenolatmofetile administration: start doses 250 mg, increase of the daily dose about 250 mg every week till reaching 2 g/daily<br>* Other names: Cellcept;Drug: Cyclosporin A<br>* 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<br>* Other names: Sandimmun optoral;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function evaluated by serum creatinine at month 12 and month 24 |  | month 12 and month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular risk factors at month 12 and month 24 |  | month 12 and month 24 | 
| Acute rejection episodes, gastrointestinal disorders and other adverse events at month 12 and month 24 |  | month 12 and month 24 | 
| Quality of life assessed by the SF36, spiroergometry, concomitant medication at month 12 and month 24 |  | month 12 and month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cyclosporine, Glucocorticoids, renal insufficiency, chronic, long-term care