ACE-inhibitors in Extracapillary Glomerulonephritis (EXTRA)

M

Monia Lorini

Status and phase

Unknown
Phase 2

Conditions

Extracapillary Glomerulonephritis

Treatments

Drug: Lisinopril

Study type

Interventional

Funder types

Other

Identifiers

NCT02682459
2015-003884-12 (EudraCT Number)
EXTRA

Details and patient eligibility

About

The natural course of extracapillary glomerulonephritis is severe leading to End-Stage Renal Disease (ESRD) or death in most cases. Despite immunosuppressive treatment, long-term renal outcome remains poor since active crescents usually progress to fibrotic scars with glomerular occlusion and disruption.In experimental models Angiotensin Converting Enzyme (ACE)-inhibitor therapy targeting the over-expression of angiotensin type 1 (AT1) receptors, that are responsible for dysregulated proliferation of parietal cell progenitors, blocks the formation of crescents and their fibrotic evolution. Should these drugs have similar effects in humans, ACE-inhibitor therapy on top of standard immunosuppression might be instrumental to prevent ESRD and promote renal function recovery in clinical practice.

Enrollment

22 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • 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:

    1. Type I: Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis,
    2. Type II: Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis;
    3. 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 idiopathic immune complex glomerulonephritis.
  • Clinical indication to immunosuppressive therapy;

  • No specific indication to treatment with Renin Angiotensin System (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/1.73m2);
  • 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 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

22 participants in 2 patient groups

Lisinopril
Experimental group
Description:
Patients will receive, in addition to standard immunosuppressive therapy, lisinopril starting with 5 mg/day, then progressively up-titrated to reach the maximum tolerable dose (target dose) for 18 months.
Treatment:
Drug: Lisinopril
No intervention
No Intervention group
Description:
Patients will receive only the standard immunosuppressive therapy.

Trial contacts and locations

2

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Central trial contact

Ettore Sabadini, MD; Barbara Ruggiero, MD

Data sourced from clinicaltrials.gov

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