Everolimus and Low Dose CNI Compared With MMF and Full CNI Dose in Heart Transplanted Patients: One Year Follow up (CRAD001AILO2)

Phase IV: Effect of Everolimus and CNI Minimalization on Renal Function.

The different mechanisms of action of Everolimus and cyclosporine suppress immune function in synergistic manner. Thus it is postulated that the use of Everolimus in combination with cyclosporine permits a significant cyclosporine dose reduction without loss of immunosuppressive activity in the clinical setting.

The aim of the present study is to evaluate the evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.

Study Overview

• Status: Completed
• Conditions: Chronic Rejection of Cardiac Transplant
• Intervention / Treatment: Drug: everolimus

Detailed Description

Everolimus is a new proliferation signal inhibitor with immunosuppressive and antiproliferative activity.

The mechanism of action of Everolimus is distinct from that of calcineurin inhibitors.

Cardiac allograft vasculopathy is the major cause of late death in cardiac transplant patients.

The different mechanisms of action of Everolimus and cyclosporine suppress immune function in synergistic manner. Thus it is postulated that the use of Everolimus in combination with cyclosporine permits a significant cyclosporine dose reduction without loss of immunosuppressive activity in the clinical setting.

The aim of the present study is to evaluate the evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petah Tikva, Israel, 49100
    • Cardiology Department, Rabin Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 year
• Signed informed consent
• 6 months to 15 year after heart transplantation
• Stable heart allograft function without rejection for at least 12 months
• Same immunusuppressive drugs for at least 3 months
• CNI based immunusuppression, with Cyclosporin levels C0 100-200 ng/ml FK levels of 5-10 ng/ml for preserved CNI levels.
• Poor renal function: creatinine > 1.5 mg%.

Exclusion Criteria:

• Suspected non-compliance
• Intolerance to Everolimus
• Life expectancy < 1year
• Proteinuria > 1.5 g/24u/1.73m2
• Previous sirolimus treatment
• Patients who received any other investigational drug
• Patients with platelet count <50,000/mm³ before baseline.
• Presence of severe hypercholesterolemia (≥350 mg/dL; ≥9 mmol/L) or hypertriglyceridemia (≥750 mg/dL; ≥8.5 mmol/L)
• Patients with an absolute neutrophil count of ≤ 1,500/mm3 or white blood cell count of ≤ 4000/mm³ at baseline
• Patients with a known hypersensitivity to similar drugs and to the components of the formulations
• Patients being treated with terfenadine, astemizole, or cisapride.
• Patients who are treated with drugs strong inducers or inhibitors of cytochrome P450 3A4.
• Patients with any past (within the past 5 years) or present malignancy (other than excised basal cell carcinoma)
• Patients with clinically significant systemic infection.
• Existence of any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study medication, and/or the presence of severe diarrhea or active peptic ulcer.
• Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus, Immunosupression; everolimus and reduced dose CNI: reduced dose CNI (cyclosporine level of 50-100)with everolimus levels of 3-8.	Drug: everolimus; reduced dose CNI (cyclosporine level of 50-100)with everolimus levels of 3-8.; Other Names: certican

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The occurrence of major adverse cardiovascular events	1 year

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Tuvia Ben Gal, MD, Rabin Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: January 8, 2008
• First Submitted That Met QC Criteria: January 16, 2008
• First Posted (Estimate): January 17, 2008

Study Record Updates

• Last Update Posted (Estimate): July 29, 2011
• Last Update Submitted That Met QC Criteria: July 28, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Renal function, heart transplant, everolimus
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: 004765