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

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

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 Overview

• Status: Unknown
• Conditions: Cardiac Transplantion
• Intervention / Treatment: Drug: Ciclosporine 130 µg/l < T0 ciclosporinemia < 200 µg/l; Drug: Ciclosporine 200 µg/l < T0 ciclosporinemia < 300 µg/l

• Study Type: Interventional
• Enrollment: 106
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69677
    • Pascale BOISSONNAT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
systolic and diastolic blood pressure
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)
fasting glycemia, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Pascale BOISSONNAT, MD, Hospices Civils de Lyon

Publications and helpful links

General Publications

• Boissonnat P, Gaillard S, Mercier C, Redonnet M, Lelong B, Mattei MF, Mouly-Bandini A, Pattier S, Sirinelli A, Epailly E, Varnous S, Billes MA, Sebbag L, Ecochard R, Cornu C, Gueyffier F. Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial. Trials. 2012 Dec 3;13:231. doi: 10.1186/1745-6215-13-231.

Study record dates

Study Major Dates

• Study Start: March 1, 2004

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): April 27, 2007
• Last Update Submitted That Met QC Criteria: April 26, 2007
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: immunosuppressive; Cardiac Transplant; ciclosporine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 2003.325