Does Ramipril Lower the Amount of Protein in the Urine for Kidney Transplant Patients taking Sirolimus

• Conditions: Prophylaxis of organ rejection in renal allograft recipients; MedDRA version: 14.1Level: LLTClassification code 10050436Term: Prophylaxis against renal transplant rejectionSystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2007-001675-11-PL
• Lead Sponsor: Wyeth Pharmaceuticals, a Pfizer Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-09
• Last Update Posted: 3 February 2014

Recruitment & Eligibility

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

Inclusion Criteria

Age equal to or greater than 18 years.

Receiving cyclosporine (CsA) or tacrolimus since the first month post-transplant.

In addition to a calcineurin inhibitor, the subject must be treated with at least one of the following drugs:
• MMF (=500 mg/day), Mycophenolate sodium (MPS) (=360 mg/day) or AZA (=50 mg/day)
• Corticosteroids (2.5 to 15 mg/day for prednisone or prednisolone or 2 to 12 mg/day for methylprednisolone or the alternate day equivalent)
• If subject is on a steroid-free regimen, the subject must be steroid-free for a minimum of 12 weeks before randomization.

Subject is 3 to 60 months after renal transplantation.

Subject is greater than 12 weeks after treatment for any acute rejection.

Blood pressure is equal to or less than 140/90 mm/Hg (determined by the average of three successive readings at the screening visit).

Women of childbearing potential (CBP) with a negative pregnancy test at screening, men, post-menopausal women.

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 332
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 43

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 4 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 of the protocol:Equation for calculating Glomerular Filtration Rates.)
- Subjects with a U p/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 equal to or less than 140 mmHg.
- Baseline histology score of equal to or greater than Banff grade II chronic allograft score on any prior renal transplant biopsy according to the updated Banff 1997 criteria as stated in attachment 6 of the protocol.
- 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 a history of primary or recurrent FSGS, membranous glomerulonephreitis (MGN) or membranoproloferative glomerulonephritis (MPGN).
- Evidence of any 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 sirolimus 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.
- Immunosuppressive therapies other than those described in Protocol Section 13.
- Planned systemic 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; hemoglobin equal to or less than 10 g per litre; absolute neutrophil 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) either in the presence or absence 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 human immunodeficiency virus (HIV) positive.
- Subjects with severe hepatic impairment (defined as Grade C Child-Pugh score).

Exclusion criteria for sirolimus conversion
Subjects with any of the following conditions or characteristics at the post ra

Study & Design

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