Heart Transplant
Conditions
Interventions
Trade Name: Rapamune
Product Name: Rapamune
Pharmaceutical Form: Coated tablet
INN or Proposed INN: sirolimus
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy and safety, including the effect on renal function of sirolimus (Rapamune?) replacing CNI after 3 months in a standard care regimen of CNI, MMF and steroids compared to a standard care regimen of CNI, MMF and steroids in heart transplant patients;Secondary Objective: •Incidence of BPAR (and freedom from BPAR) at 6, 12 and 24 months •Number of episodes of BPAR per patient at 6, 12, and 24 months •Time to first BPAR •Incidence of re-transplant at 6, 12 and 24 months •Incidence of death at 6, 12 and 24 months •Incidence of treated rejection including antibody treated rejection •Incidence of antibody treated rejection (and freedom from antibody treated rejection) •Incidence of any episode of rejection associated with HDC •Time to graft loss at 6, 12 and 24 months •Time to death at 6, 12 and 24 months •Time to composite primary endpoint •IVUS end points at 12 months •Incidence of treatment failure at 12 and 24 months defined as e.g. •Renal function assessed by calculated GFR •Renal function defined by the difference in the slope of the 1/ SCr. plot at 6, 12, and 24 months •Protein / creatinine ratio at 6, 12 and 24 months •Safety between treatment groups (at 2 years unless otherwise indicated) as measured by;Primary end point(s): Renal function (% change from randomization) assessed by calculated GFR utilizing MDRD-6 at 24 months post transplant (21 months post-randomization) and a composite endpoint of incidence of biopsy proven acute rejection or HDC, or graft loss (re-transplantation or death) or lost to follow-up in the interval between randomization and 12 mos post-transplant (9 mos after randomization). | — |
Countries
Austria, Belgium, Czech Republic, Spain, United Kingdom
Outcome results
None listed