A prospective, open label, randomized, multicenter, multinational study evaluating the overall efficacy and safety including the effect on renal function of sirolimus (Rapamune?) replacing CNI in a standard care regimen of CNI, mycophenolate mofetil (MMF) and steroids in heart transplant patients

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 650

Inclusion Criteria

1.Patients, age > 18
2.Patients receiving their first heart transplant (single organ transplant)
3.Patients on a standard care regimen of CNI, MMF and steroids since transplantation
4.Patients capable of understanding the purposes and risks of the study and who can give written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria at Study Entry (4-6 weeks post-transplant):
1.Women of childbearing potential with a positive serum or urine pregnancy test or nursing mothers. Females of childbearing potential not using 2 reliable forms of contraception, including a barrier method, for the duration of the study and for 90 days after the last dose of study medication.
2.Patients with a positive donor-specific cross-match at the time of transplantation
3.Patients with any PRA > 25%
4.Patients with history of malignancy other than non-melanoma skin cancer that has been totally excised and who have shown no recurrence for 2 years
5.Patients with
a)Ejection fraction of = 40%
b)Ejection fraction of 20% decrease from baseline, and the need for inotropic agents
c)Fractional shortening =20% or a 25% decrease from baseline, and the need for inotropic agents
d)Need for inotropic agents due to a Cardiac Index (CI) <2.0 L/min/m2 or a 25% decrease from baseline
6.Patients with any antibody treated acute rejection
7.Patients with known contraindications to treatment with sirolimus
8.Patients with hemoglobin < 8.5g/dL, WBC value of <3000/mm3 or a platelet count of <50,000/mm3 unlikely to resolve prior to randomization
9.Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication unlikely to resolve prior to randomization
10.Patients participating in another interventional clinical trial or requiring treatment with un-marketed investigational drugs or who would be expected to require other medications prohibited by the protocol.
11.Patients who require revascularization prior to study entry (bypass, stenting, angioplasty)

Additional Exclusion Criteria at Randomization [12 (+/- 2) weeks post-transplant]:

1.All exclusion criteria as at Study Entry
2.Patients no longer on a standard care regimen of CNI, MMF and steroids
3.Patients not on HMG CoA reductase inhibitors (statins”)
4.Patients who require dialysis within 4 weeks prior to randomization
5.Patients with any biopsy proven acute rejection = ISHLT grade 3A within 4 weeks prior to randomization
6.Patients with any biopsy proven acute rejection = ISHLT grade 3A more than 4 weeks prior to randomization without a subsequent biopsy of ISHLT grade 0 or IA
7.Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication
8.Sepsis or any severe active infection requiring IV antibiotics and/or hospitalization within the 2 weeks prior to randomization
Patients who received sirolimus before randomization

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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