Cardiac transplant recipients with mild to moderate renal insufficiency. MedDRA version: 9.1 Level: LLT Classification code 10050432 Term: Prophylaxis against heart transplant rejection
Conditions
Interventions
Trade Name: Rapamune
Product Name: Rapamune
Product Code: Rapamune
Pharmaceutical Form: Tablet
INN or Proposed INN: Sirolimus
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Wyeth Research, Division of Wyeth Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Cardiac transplant recipients aged = 18 years. 2. Receiving CsA or TAC as part of the maintenance immunosuppressive regimen since the time of transplantation. 3. = 12 Months after cardiac transplantation but = 96 months after transplantation at the time of screening. 4. GFR > 40 mL/min but 20% of GFR) over the previous 3 months. 5. Left ventricular ejection fraction by echocardiogram (ECHO) = 40%. 6. Women of childbearing potential (CBP) must have a negative urine pregnancy test before randomization. 7. Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the treatment period. 8. Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception for 3 months after discontinuation of assigned treatment. 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: 1. Secondary cardiac transplant recipients (subjects who have lost 1 or more previous cardiac transplant). 2. Multiple-organ transplant recipients (such as heart-lung, heart-kidney, or heart-after-kidney transplant recipients). 3. Treatment of acute rejection within 3 months. 4. Evidence of active systemic or localized major infection at the time of randomization. 5. Evidence of infiltrate, cavitation or consolidation on chest x-ray film obtained within 3 months before or at the time of the screening evaluation. 6. Use of any investigational drug or treatment up to 4 weeks before random assignment. 7. Spot urine protein-to-creatinine ratio > 0.5 or proteinuria > 500 mg/day. 8. Subjects maintained on CNI monotherapy. 9. Prior or current use of mammalian target of rapamycin (mTOR) inhibitors unless administration was part of a "CNI holiday" (a planned temporary switch from a CNI to an mTOR inhibitor to limit exposure to CNIs) lasting no more than 10 days. 10. Known hypersensitivity to sirolimus or its derivatives or macrolide antibiotics. 11. Treatment with voriconazole, cisapride, or ketoconazole, which are all known to interact with sirolimus, that is not discontinued before randomization. 12. Treatment with aminoglycosides, amphotericin B, cisplatin, or other drugs associated with renal dysfunction that is not discontinued before randomization. 13. Subjects with screening baseline white blood cell (WBC) count 400 mg/dL (4.5 mmol/L), or total cholesterol level > 300 mg/dL (7.6 mmol/L). 14. History of malignancy within 3 years before enrollment (except for adequately treated basal-cell or squamous-ell carcinoma of the skin). 15. Planned used of agents with a known major interaction with sirolimus or CNIs. 16. Subjects who are known to be positive for human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority of converting from CNI therapy to sirolimus therapy to continuing CNI therapy with respect to renal function in cardiac transplant recipients with mild to moderate renal dysfunction.;Secondary Objective: To evaluate the safety of conversion from CNI therapy to sirolimus therapy in this patient population. To explore the effect of conversion from CNI therapy to sirolimus therapy on surrogate markers of cardiovascular risk.;Primary end point(s): Change from baseline calculated creatinine clearance (using the Cockcroft-Gault equation and adjusted for BSA using the Mosteller formula) at 52 weeks. | — |
Countries
Austria, Czech Republic, Spain
Outcome results
None listed