Renal Safety of Everolimus in Addition to Cyclosporine Microemulsion in Cardiac Transplant Recipients.

Original Study ID : CRAD001A2412

NCT ID : NCT00170794

Brief Title : Renal Safety of Everolimus in Addition to Cyclosporine Microemulsion in Cardiac Transplant Recipients.

Official Title : A One Year, Multicenter, Open-Label, Single Arm, Pilot Study of the Renal Safety of Everolimus in Addition to Cyclosporine Microemulsion in Cardiac Transplant Recipients.

Brief Summary :

The purpose of the study is to determine the extent of cyclosporine microemulsion dose reduction required to maintain stable renal function in maintenance cardiac transplant recipients, after initiation of everolimus.

Source : Novartis

Overall Status : Active, not recruiting

Start Date : September 2004

Official Title : Phase 3

Phase : Interventional

Study Design : Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Verification Date : September 2008

First Received Date : September 9, 2005

Trial Eligibility

Criteria :
Inclusion Criteria:

- Male or female cardiac transplant recipients, 18-70 years old, with established
cardiac allograft vasculopathy or at risk to develop a cardiac allograft
vasculopathy.

- Patients who are more than 12 months post-transplant and who are receiving a
cyclosporine microemulsion-based immunosuppressive regimen with/without azathioprine
/mycophenolate mofetil, with/without steroids.

- Patients need to have stable renal function with a calculated GFR exceeding 40 ml/min
(Nankivell).

- Patients without a biopsy-proven acute rejection ≥ grade 2, within 12 months prior to
study entry.

- Females of childbearing potential must have a negative serum pregnancy test within 7
days prior to enrollment. Effective contraception must be used during the trial and
for 4 weeks following discontinuation of the study medication, even where there has
been a history of infertility.

- Patients who are willing and able to participate in the full course of the study and
from whom written informed consent has been obtained.

Exclusion Criteria:

- Patients who are recipients of multiple solid organ transplants.

- Patients with a calculated GFR of less than 40 ml/min.

- Patients with a biopsy-proven acute rejection episode ≥ 2 within 12 months prior to
study entry.

- Patients who had received any investigational drug within 4 weeks prior to study
entry.

- Patients currently being treated with sirolimus or having a history of prior therapy
or having a hypersensitivity to drug similar to everolimus.

- Patient with a platelet count of < 50,000/mm3 or with a white blood cell count of ≤
2,500/mm3 or with a hemoglobin value < 10 g/dL.

- Presence of severe hypercholesterolemia (≥ 9.1 mmol/L) or hypertriglyceridemia (≥ 8.55
mmol/L).

- Patient with NYHA class IV heart failure, or with left ventricular ejection fraction
<30%. Patients with life-threatening cardiac allograft vasculopathy and/or graft
dysfunction (life expectancy 1 year).

- Patients with severe systemic infections.

- Patients who are known to have HBsAg or HCV positive hepatitis, or who are HIV
positive. Serology results obtained within 6 months prior to study entry are
acceptable. If results cannot be obtained prior to study entry, a sample must be
retained for later analysis. This stored sample will be destroyed at the end of
study.

- Patients with any past (within the last 5 years) or present malignancy other than
non-melanotic skin cancer.

- Existence of a co-morbid condition likely to result in death prior to study
completion

- Symptoms of significant mental illness, which in the opinion of the investigator may
interfere with the patient's ability to comply with the protocol. History of drug or
alcohol abuse within 1 year of baseline.

- Inability to cooperate or communicate with the investigator.

- Female patients of childbearing potential who are planning to become pregnant, who are
pregnant and/or lactating, or who are unwilling to use effective means of
contraception.

Gender : Both

Minimum Age : 18 Years

Maximum Age : 70 Years

OutComes

Primary OutComes

Measure : Comparing calculated glomerular filtration rate (GFR) at Month 3 (Week 12) to Baseline and by comparing the daily cyclosporine dose at Month 3 (Week 12) to Baseline.

Secondary OutComes

Measure : Incidence of acute rejection episode greater than or equal to grade 3A.

Measure : Safety laboratory tests including lipid profiles, hematology and proteinuria.

Measure : Incidence of premature study treatment discontinuation.

Measure : Incidence of serious adverse avents (SAEs).

Measure : Incidence of admission to the hospital.

Interventions

Type : Drug

Name : Everolimus (RAD001)

Clinical Trial Name - Renal Safety of Everolimus in Addition to Cyclosporine Microemulsion in Cardiac Transplant Recipie