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ACE-inhibitors in Extracapillary Glomerulonephritis (EXTRA)

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ClinicalTrials.gov Identifier: NCT02682459
Recruitment Status : Recruiting
First Posted : February 15, 2016
Last Update Posted : April 6, 2018
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
Monia Lorini, A.O. Ospedale Papa Giovanni XXIII

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Extracapillary Glomerulonephritis Drug: Lisinopril Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : February 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Lisinopril

Arm Intervention/treatment
Experimental: Lisinopril
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.
Drug: Lisinopril
No Intervention: No intervention
Patients will receive only the standard immunosuppressive therapy.



Primary Outcome Measures :
  1. The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy. [ Time Frame: Changes from baseline and 6 and 18 month. ]

Secondary Outcome Measures :
  1. Expression of parietal cell proliferation markers at glomerular level, graded on a scale of 0 to 3 (0: no staining, 1: mild, 2: moderate, 3: strong diffuse [ Time Frame: Changes from baseline and 6 and 18 month. ]
  2. Number of fibrosclerotic crescents [ Time Frame: Changes from baseline and 6 and 18 month. ]
  3. Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance [ Time Frame: Changes from baseline and 6, 12 and 18 month. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02682459


Contacts
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Contact: Barbara Ruggiero, MD 0039 035 45351 barbara.ruggiero@marionegri.it
Contact: Ettore Sabadini, MD esabadini@asst-pg23.it

Locations
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Italy
Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò Recruiting
Ranica, Bergamo, Italy, 24020
Sub-Investigator: Barbara Ruggiero, MD         
ASST Papa Giovanni XXIII Recruiting
Bergamo, Italy, 24147
Principal Investigator: Giuseppe Remuzzi, MD         
Sub-Investigator: Ettore Sabadini, MD         
Sub-Investigator: Piero Ruggenenti, MD         
Sponsors and Collaborators
Monia Lorini
Istituto Di Ricerche Farmacologiche Mario Negri

Publications:
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Responsible Party: Monia Lorini, EC Secretary, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier: NCT02682459     History of Changes
Other Study ID Numbers: EXTRA
2015-003884-12 ( EudraCT Number )
First Posted: February 15, 2016    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Monia Lorini, A.O. Ospedale Papa Giovanni XXIII:
Extracapillary glomerulonephritis
crescentic glomerulonephritis
rapidly progressive renal failure
chronic kidney disease
ACE-inhibitors
fibrosis
Additional relevant MeSH terms:
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Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases
Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs