ERKNet

The European Rare Kidney Disease Reference Network

  

Research Project

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

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