LOW CYCLO: Study Evaluating the Benefit of Two Doses of Ciclosporine in de Novo Cardiac Transplant

Study Overview
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Brief Summary
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Primary Objective: Evaluation of the benefit on renal function of one year of a low dose of ciclosporine versus the usual dose Secondary Objective: To evaluate the immunosuppressive efficacy and tolerance of the treatment Study Duration: Twelve months for each patient Study Treatment: Ciclosporine Group A: low dose >= 130 µg/l < T0 ciclosporinemia < 200 µg/l; Group B: standard dose >= 200 µg/l < T0 ciclosporinemia < 300 µg/l. Study Visits: One visit every 15 days, for the first three months; then 1 visit every month, for 6 months; and 1 visit at 9 and 12 months. Associated Treatments: Mycophenolate (Cellcept®), 3g a day Corticoids, as used for transplanted patients Randomization: Randomization will occur when it is decided that ciclosporine will be introduced.

Official Title
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LOW CYCLO: A Multicenter, Prospective, Randomized Study Evaluating the Benefit, on Renal Function, of Two Doses of Ciclosporine: Low Dose Versus Usual Dose, in Association With Mycophenolate and Corticoïds, in de Novo Cardiac Transplant

Conditions
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Cardiac Transplantion

Intervention / Treatment
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* Drug: Ciclosporine 130 µg/l < T0 ciclosporinemia < 200 µg/l
* Drug: Ciclosporine 200 µg/l < T0 ciclosporinemia < 300 µg/l


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient: Males or females, ages > 18 < 65. First cardiac transplant. Negative pregnancy test for females of childbearing potential, at screening. Efficient method of contraception must be used during the study. Written informed consent. Donor: Cold ischemia duration < 6 hours Exclusion Criteria: Recipient: Unstable hemodynamic status at randomization. Patient with assisted circulation, considered unstable. Serum creatinine > 250 µmol/l. Nursing or pregnant females. HIV positive. PCR hepatitis C virus (HCV) positive or hepatitis B surface (Hbs) antigen positive (within 6 months prior to study). Multi-organ graft or retransplant. History of cancer (evolving, or within 5 years, except for epidermoid or basocellular localised cutaneous carcinoma). Use of any investigational product and/or participation in another clinical research study within the last 30 days prior to study entry. Any substance abuse or any psychiatric disorder Contra-indication to study treatments. Unable to introduce ciclosporine within 4 days after transplant. Donor: Known coronary pathology or cardiac disease. HBsAg positive or HCV positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ciclosporine 130 µg/l < T0 ciclosporinemia < 200 µg/l|nan|
|Drug: Ciclosporine 200 µg/l < T0 ciclosporinemia < 300 µg/l|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of renal function, as assessed by the evolution between the two treatment groups at 12 months versus baseline serum creatinine level |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under curve of creatinine at 12 months |  |  | 
| Cystatin C level at 1, 2, 3, 6 and 12 months |  |  | 
| Creatinine clearance at 6 and 12 months |  |  | 
| Proteinuria and microalbuminuria at 6 and 12 months |  |  | 
| Secondary outcomes include those linked to the immunosuppressive efficacy and tolerance of the treatment: Difference in appearance incidence of acute graft reject and adverse events |  |  | 
| Myocardial biopsy (International Society of Heart and Lung Transplantation [ISHLT] grades) |  |  | 
| Difference in the evolution of left ventricular function and cardiovascular risk factors between the two groups at 6 and 12 months versus baseline: left ventricular ejection fraction and shortening fraction (echocardiogram) |  |  | 
| systolic and diastolic blood pressure |  |  | 
| fasting glycemia, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Transplant, ciclosporine, immunosuppressive