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

Hospices Civils de Lyon106 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

106

Conditions

Cardiac Transplantion

Interventions

Ciclosporine 130 µg/l < T0 ciclosporinemia < 200 µg/l

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Evolution of renal function, as assessed by the evolution between the two treatment groups at 12 months versus baseline serum creatinine level

Secondary Outcomes

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