To test in a pilot trial the efficacy and tolerance of sirolimus oral (at low doses) in patient to treat poor-prognosis IgA Nephropathy.
Conditions
Interventions
Trade Name: RAPAMUNE
Product Name: SIROLIMUS
Pharmaceutical Form: Oral solution
INN or Proposed INN: Sirolimus
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration
Sponsors
NEPHROLOGY DEPARTMENT (HOSPITAL UNIVERSITARY OF BELLVITGE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age 18 to 70 and with capacity to grant informed consent 2. Biopsy-proven grade II or III IgA nephropathy by means of standard immunochistochemical and morphological criteria (see Annex 4). 3. Renal biopsy in the in the 3 months prior to randomization date. 4. Absence of known hepatic, cardiac, pulmonary or intestinal disease 5. Mild renal failure: glomerular filtrate estimated by Cockroft-Gault, more than 60 ml/min. 6. Any of the following clinical states: a) High blood pressure defined as systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg associated wit proteinuria between 0.3-1 g/day and/or microhematuria. b) Proteinuria higher than 1g/day. 7. Women of child-bearing age will follow a suitable contraceptive method, and a negative pregnancy test will be needed before inclusion in the study 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.Serology positive for HIV or hepatitis B infection (defined as positive for the HbsAg antigen) or hepatitis C infection (defined as viral RNA detection) 2. Treatment with steroids or immunosuppressors in the two previous years. 3. Evidence of active infection at the time of inclusion in the study. 4. Pregnancy or lactancy at the time of inclusion in the study.. 5. Estimated glomerular filtration 2 mg/dl, or ALT or AST two times higher than the normal upper limit. 6. Diabetes Mellitus, defined as patients treated with insulin or oral antidiabetics or glucaemias higher than 140 mg/dl in two or more episodes. 7. Poor control of high blood pressure (defined as systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg, taking 3 or more antihypertensives) or evidence or suspicion of renovascular disease. 8. Thrombocytopenia less than 100,000 /mm3 or total neutrophil value lower than 2000 /mm3 or triglycerides value > 400 mg/dL (4.6 mmol/L) or cholesterol > 300 mg/dL (7.8 mmol/L) or LDL > 200 mg/dL. 9. IgA nephropathy systemic forms, i.e., Schönlein-Henoch purpura, IgA nephropathy secondary forms, post-renal transplant IgA nephropathy recurrences, cases presented in the form of rapidly progressive renal failure and cases with the presence of cellular crescents in more than 50% of the glomeruli will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect at month 12th of the administration of Rapamune? on a clinical composite variable (change in proteinuria, blood pressure and hematuria) in patients with IgA nephropathy with poor prognosis criteria. ;Primary end point(s): -Change in a composite clinical variable resulting from evolution of proteinuria figures measured at months 6th and 12th, blood pressure measured at month 6th and 12th and hematuria at month 6th and 12th. ;Secondary Objective: a) Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) at months 6th and 12th, and comparison between both arms. b) Change in renal histology at 12 months. c) Percentage of patients who withdraw from the study medication due to adverse events. d) Percentage of patients with therapeutic failure | — |
Countries
Spain
Outcome results
None listed