E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Profilaxis del rechazo de órgano en receptores de injerto renal
Prophylaxis of organ rejection in renal allograft recipients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050436 |
E.1.2 | Term | Prophylaxis against renal transplant rejection |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of ramipril in preventing a urinary protein to creatinine ration (U p/c) of 0.5 or greater following conversion to sirolimus from a calcineurin inhibitor (CNI) (either TAC or CsA) in maintaenance renal transplant patients.
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the safety of ramipril in maintenance renal transplant patients following sirolimus conversion 2) To evaluate the effect of losartan in maintenance renal transplant patients where ramipril or placebo is ineffective in controlling proteinuria. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to Losartan therapy initiation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last follow up visit for safety of last randomised subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |