Glomerulonephritis, IGA, IGA Nephropathy, Nephropathy, IGA
Conditions
Keywords
Nephropathy, IGA, Pilot trial, Sirolimus, Rapamune
Brief summary
The purpose of this study is to test in a pilot trial the efficacy and tolerance of sirolimus oral (at low doses) in patient to treat poor-prognosis IgA Nephropathy.
Interventions
DRUGACE inhibitor + statin
sirolimus starting at 1 mg/d (target 3-6 ng/ml) plus enalapril starting at 5 mg/d to control blood pressure plus atorvastatin starting at 10 mg/d
DRUGSirolimus (study drug)+ACE inhibitor + statin
enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Josep m Cruzado
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 70 and with capacity to grant informed consent * Biopsy-proven IgA nephropathy by means of standard immunohistochemical and morphological criteria * Renal biopsy in the in the 3 months prior to randomization date * Absence of known hepatic, cardiac, pulmonary or intestinal disease * Glomerular filtrate estimated by Cockcroft-Gault, more than 30 ml/min * 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 with proteinuria between 0.3-1 g/day and/or microhematuria. b) Proteinuria higher than 1g/day * Women of child-bearing age will follow a suitable contraceptive method, and a negative pregnancy test will be needed before inclusion in the study
Exclusion criteria
* Serology positive for HIV or hepatitis B infection (defined as positive for the HbsAg antigen) or hepatitis C infection (defined as viral RNA detection) * Treatment with steroids or immunosuppressors in the two previous years * Evidence of active infection at the time of inclusion in the study * Pregnancy or breastfeeding at the time of inclusion in the study * Estimated glomerular filtration \< 30 ml/min, bilirubin \> 2 mg/dl, or ALT or AST two times higher than the normal upper limit * Diabetes Mellitus, defined as patients treated with insulin or oral antidiabetics or glycemias higher than 140 mg/dl in two or more episodes * 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 * 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 * 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 * History of cancer in the previous 5 years,exception of skin basocellular carcinoma and uterine in situ carcinoma (completely removed both of them) * Know intolerance to Sirolimus or macrolides
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the effect 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 | at month 12th |
Secondary
| Measure | Time frame |
|---|---|
| Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) and comparison between both arms | At months 6th and 12th |
| Change in renal histology | At 12 months |
| Percentage of patients who withdraw from the study medication due to adverse events | Within 1 year |
| Percentage of patients with therapeutic failure | Within 1 year |
Countries
Spain
Outcome results
None listed