ERKNet
The European Rare Kidney Disease Reference Network
Project Title: |
A pilot, prospective, randomized, open-label, blinded endpoint (PROBE) histopathology trial to assess the effects of ACE-inhibition therapy on glomerular proliferative lesions in patients with extracapillary glomerulonephritis (EXTRA study) |
Project Type: |
Clinical Trial, Enrolment ongoing Adjunct biobank: DNA, Serum, Plasma |
Disease group(s): |
Immune glomerulopathies |
Project Summary: |
Aims of the study To evaluate whether ACE-inhibitor therapy on top of immunosuppression is able to reduce the extent of extracapillary proliferation as compared to immunosuppressive therapy alone. Primary outcomes Extent of extracapillary proliferation on light microscopy (% of total glomeruli with proliferative lesions) at posttreatment repeat biopsy. Secondary outcomes - Crescent score or crescent index. - Expression of the parietal cell proliferation markers CD24, CD133, CXCR4, SDF-1, nephrin, and AT1 receptor and of macrophage migration and activation markers CD68, MMP-12 by immunohistochemistry (grading 0 to 3, where 0=no staining, 1=mild, 2=moderate, 3=strong diffuse). - Number of fibrosclerotic crescents versus baseline. - GFR as measured by the iohexol plasma clearance, sodium, albumin and total IgG fractional clearances at baseline, 6, 12 and 18 months. - Cumulative and mean daily doses of concomitant immunosuppressive treatments, number of plasmaexchange sessions and hemodialysis sessions to treat acute renal failure. - Time to chronic hemodialysis. - Treatment costs. Inclusion criteria - Males and females. - Adult age (>18 years old). - Rapidly progressive renal failure associated with acute nephritic syndrome and/or nephrotic syndrome. - Histology evidence of extracapillary proliferation with less than 50% of sclerotic glomeruli and associated with: Type I Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis; Type II Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis; Type III Immune-complex mediated glomerular diseases (Proliferative lupus nephritis (LN), IgA nephropathy (IgAN)/ Schönlein-Henoch purpura, Type I membranoproliferative glomerulonephropathy (MPGN), Primary or secondary membranous nephropathy (MN), Primary or idhiopatic immune complex glomerulonephritis). - Clinical indication to immunosuppressive therapy. - No specific indication to treatment with RAS inhibitors such as heart failure or coronary ischemic disease. - Written informed consent. Exclusion criteria - Pre-existing advanced chronic renal failure (creatinine clearance less than 20 mL/min/1.73msq). - Evidence of B or C virus active infection. - HIV infection. - Recent diagnosis of malignancy. - Prolonged bleeding time and any other contraindication to kidney biopsy evaluation. - Any specific contraindication to ACE inhibitor therapy (that is: history of angioedema a or other treatment-related serious adverse events). - Pregnancy or lactating. - Women of childbearing potential without following a scientifically accepted form of contraception. - Inability to understand the risks and benefit of the study or evidence of an uncooperative attitude. - Legal incapacity. |
Lead principal investigator(s): |
Giuseppe Remuzzi, Bergamo |
Co-investigator(s): |
Piero Ruggenenti, Bergamo Ettore Sabadini, Bergamo |
Project Period: |
04/2016 - 12/2020 |
Sponsors: |
Non-profit foundation |
Project web page: |
http://registro.marionegri.it/frontend_eng/interno.php?id_studio=250 |
ClinicalTrials.gov: |
NCT02682459 |
EudraCT Nr.: |
2015-003884-12 |