Exchange of Azathioprine by Mycophenolatmofetile and Cyclosporine A Dose Reduction After Heart Transplantation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to improve or save renal function by optimizing the immunosuppressive regimen by reducing the Cyclosporine A dose and the exchange of Azathioprine by Mycophenolatmofetile, which is an effective immunosuppressive agent and will minimize the risk of acute rejection episodes.

Detailed Description
-----------------
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.Long-term administration of calcineurin inhibitors is associated with chronic nephrotoxicity.

Official Title
-----------------
Conversion Study to Optimize Immunosuppressive Regimen by Exchange of Azathioprine by Mycophenolatmofetile and Cyclosporine A Dose Reduction for Patients After Heart Transplantation in Lon-Term

Conditions
-----------------
Heart Transplantation

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Current immunosuppressive regimen: Cyclosporine A, Azathioprine and corticosteroids for at least 12 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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>Azathioprine administration: was stopped at day 0; Mycophenolatmofetile administration: was started with 250 mg/daily at day 1, the start dose was increased about 250 mg/daily every week till 2 g/daily; Cyclosporin A reduction: Cyclosporin A trough level reduction started after week 8. The new target range was 50 to 90 ng/ml | Drug: Mycophenolatmofetile<br>* Mycophenolatmofetile administration: was started with 250 mg/daily at day 1, the start dose was increased about 250 mg/daily every week till 2 g/daily<br>* Other names: CellCept;Drug: Cyclosporin A<br>* Cyclosporin A reduction: Cyclosporin A trough level reduction started after week 8. The new target range was 50 to 90 ng/ml<br>* Other names: Sandimmun optoral;|

What is the study measuring?
-----------------
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 |
| --- | --- | --- |
| acute rejection episodes, gastrointestinal disorders and other adverse events at month 12 and month 24 |  | month 12 and month 24 | 
| Cardiovascular risk factors 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cyclosporine, renal insufficiency, chronic, long-term care