A Randomized, Placebo Controlled, Double-Blind Comparative Study Evaluating the Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus - ND

• Conditions: Prophilaxyas of organ rejection in renal allograft recipients; MedDRA version: 9.1Level: PTClassification code 10048870Term: Prophylaxis against transplant rejection

• Registration Number: EUCTR2007-001675-11-IT
• Lead Sponsor: Wyeth Parmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-08
• Last Update Posted: 10 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 375

Inclusion Criteria

1.Age ≥ 18 years at the time of screening. 2.Treatment with corticosteroids at a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone), the alternate day equivalent, or a steroid-free regimen, for a minimum of 12 weeks before randomization. Subjects may be treated with either MMF (>500mg/day), Mycophenolate sodium (MPS) (>360 mg/day) or AZA (>50 mg/day) and must be on a minimum of two immunosuppressive drugs if on a steroid-free regimen. 3.Receiving cyclosporine (CsA) or tacrolimus since the first month post-transplant 4.Subject is 6 to 60 months after renal transplantation. 5.Subject is greater than 12 weeks after treatment for any acute rejection. 6.Blood pressure is < 140/90 mm/Hg taken as defined below (average of 3 readings at the screening visit). 7.Men, post-menopausal women or women of childbearing potential (CBP) with a negative pregnancy test at screening. 8.Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study. 9.Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception for 3 months following 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

1. Subjects who, in the opinion of the investigator, are not able to complete the study. 2. Recipients of multiple organ transplants (i.e., prior or concurrent transplantation of a non-renal allograft). 3. Subjects who are currently receiving, or have received within 8 weeks before enrollment, RAAS blockade. 4. Subjects with a calculated glomerular filtration rate (GFR) < 40 mL/min (per the Modification of Diet in Renal Disease [MDRD-7] or abbreviated MDRD formula). 5. Subjects with a Up/c, or a U alb/c of >0.3 collected as defined below. 6. Subjects with a history of uncontrolled systolic blood pressure defined as those subjects who cannot achieve a sustained systolic blood pressure of < 140 mm Hg. 7. Baseline histology score ≥ Banff grade II chronic allograft score on any prior renal transplant biopsy. 8. Subjects with a history of biopsy-proven acute rejection within 12 weeks before enrollment. 9. Any prior exposure to a mammalian target of rapamycin (mTOR) inhibitor 10. Subjects with primary or recurrent focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), or membranoproliferative glomerulonephritis (MPGN). 11. Evidence of any active systemic or localized major infection. 12. Evidence of infiltrate, cavitation, or consolidation on any prior chest x-ray obtained within the previous year or a prior history of pulmonary or extra pulmonary tuberculosis. 13. Use of any investigational drug or treatment up to 4 weeks prior to enrollment. 14. Known hypersensitivity to sirolimus or its derivatives, macrolide antibiotics, ACEIs, ARBs, corticosteroids, AZA, or inosine monophosphate dehydrogenase (IMPDH) inhibitor. 15. Planned use of agents with a known interaction with any of the following: sirolimus or its derivatives, macrolide antibiotics, ACEIs, ARBs, corticosteroids, AZA, or IMPDH inhibitor. 16. Immunosuppressive therapies other than CsA, TAC, AZA, MMF, MPS, and corticosteroids. 17.Planned treatment with voriconazole, cisapride, or ketoconazole that will not be discontinued prior to randomization. 18. Prior treatment with aminoglycosides, amphotericin B, cisplatin, or other drugs associated with renal dysfunction that is not discontinued at least 2 weeks prior to the screening/baseline visit. 19. Subjects with a screening/baseline total white blood cell count ≤ 2,000/mm3, absolute neutrophil count (ANC) ≤ 1000/mm3 or platelet count ≤ 100,000/mm3. 20. Fasting triglyceride level ≥ 400 mg/dL (≥ 4.5 mmol/L), fasting total cholesterol level ≥ 300 mg/dL (≥ 7.8 mmol/L), or fasting low-density lipoprotein (LDL)-cholesterol level 160 mg/dL (4.13 mmol/L) despite the use of optimal lipid-lowering therapy. 21. History of malignancy within 3 years before enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin. 22.Subjects who are known to be human immunodeficiency virus (HIV) positive. Exclusion Criteria for Sirolimus Conversion The presence of any of these at the week 4 post randomization visit, while on ramipril or placebo, will preclude SRL conversion: 1.Subjects with a calculated GFR < 40mL/min (per MDRD-7 or abbreviated MDRD formula). 2.Subjects with a U p/c or U alb/c of >0.3. 3.Blood pressure >140/90 mmHg on 3 successive determinations 4.Biopsy-confirmed acute rejection during the 4 weeks following enrollment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified