A Randomised, Placebo Controlled, Double-Blinded Comparative Study Evaluating the Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Translplant Patients Converted to Sirolimus

Conditions: Prophylaxis of organ rejection in renal allograft recipients
MedDRA version: 9.1Level: LLTClassification code 10050436Term: Prophylaxis against renal transplant rejection

Registration Number: EUCTR2007-001675-11-FR

Lead Sponsor: Wyeth Pharmaceuticals

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 375

Inclusion Criteria

Age equal to or greater than18 years.
Treatment with corticosteroids at a dosage range of 2.5 to 15mg/day for prednisone or prednisolone (2 to 12 mg/day for methylpredniisolone), the alternate day equivalent, or a steroid-free regimen for a minimum of 12 weeks before randomisation. Subjects may be treated with either MMF (greater than 500mg/day),mycophenolate sodium (MPS) (greater than 360mg/day) or AZA (greater than 50mg/day)and must be taking a minimum of 2 immunosuppressive drugs if on a steroid-free regimen.
Receiving CsA or TAC since the first month post-transplant.
Subject is 6 to 60 months after renal transplantation.
Subject is greater than 12 weeks after treatment for any acute rejection.
Blood pressure is less than 140/90 mm/Hg (determined by the average of three successive readings at the screening visit).
End-stage renal disease, with subjects scheduled to receive a primary or secondary renal allograft from a cadaveric, a living-unrelated, or a living-related donor.
Men, post-menopausal women or women of childbearing potential (CBP) with a negative pregnancy test at screening.
Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study.
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 the assigned therapy.
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

Subjects who, in the opinion of the investigator, are not able to complete the study.
Recipients of multiple organ transplants (i.e. prior or concurrent transplantation of a non-renal allograft).
Subjects who are currently receiving, or have received within 8 weeks before enrollment, RAAS blockade.Subjects with a calculated GFR of less than 40 mL/min (per the Modification of Diet in Renal Disease [MDRD-7] or abbreviated MDRD formula; Attachment 1:Equation for calculating Glomerular Filtration Rates.)
Subjects with a U p/c, or a urine albumin to creatinine ratio (U alb/c) of greater than 0.3.
Subjects with a history of uncontrolled systolic blood pressure defined as those subjects who cannot achieve a sustained systolic blood pressure of less than 140 mmHg.
Baseline histology score of equal to or greater than Banff grade II chronic alograft score on any prior renal transplant biopsy.
Subjects with a history of biopsy-proven acute rejection within 12 weeks of enrollment.
Any prior exposure to a mammalian target of rapamycin (mTOR) inhibitor.
Subjects with primary or recurrent FSGS, membranous glomerulonephreitis (MGN) or membranoproloferative glomerulonephritis (MPGN).
Evidence of active systemic or localized major infection.
Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained within the previous year or a prior history of pulmonary or extra pulmonary tuberculosis.
Use of any investigational drug or treatment up to 4 weeks before enrollment.
Known hypersensitivity to SRL or its derivatives, macrolide antibiotics, ACEIs, ARBs, corticosteroids, AZA, or inosine monophosphate dehydrogenase (IMPDH) inhibitor.
Planned use of agents with a known interaction with any of the following: SRL or its derivatives, macrolide antibiotics, ACEIs, ARBs, corticosteroids, AZA, or IMPDH inhibitor.
Immunosuppression therapies other than those described in Protocol Section 16.
Planned treatment with voriconazole, cisapride or ketoconazole that will not be discontinued before randomization.
Prior treatment with aminoglycosides, amphotericin B, cisplatin, or other drugs associated with renal dysfunction that is not discontinued at least 2 weeks before the screening/baseline visit.
Subjects with a screening/baseline total white blood cell count (WBC) of equal to or less than 2,000/mm; absolute neurtophil count (ANC) of equal to or less than 1000/mm, or platelet count equal to or less than100,000/mm.
Fasting triglyceride level of equal to or greater than 400 mg/dL (or equal to or greater than 4.5 mmol/L); fasting total cholesterol level of equal to or greater than 300 mg/dL (or equal to or greater than 7.8 mmol/L), or fasting low-density lipoprotein (LDL)-cholesterol level equal to or greater than 160 mg/Dl (or equal to or greater than 4.13 mmol/L) despite the use of optimal lipid lowering therapy.
History of malignancy within 3 years before enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin.
Subjects who are known to be HIV positive.