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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

Tracking Information
First Submitted Date  ICMJE February 10, 2016
First Posted Date  ICMJE February 15, 2016
Last Update Posted Date April 6, 2018
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2016)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02682459 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2016)
  • 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. ]
  • Number of fibrosclerotic crescents [ Time Frame: Changes from baseline and 6 and 18 month. ]
  • Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance [ Time Frame: Changes from baseline and 6, 12 and 18 month. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ACE-inhibitors in Extracapillary Glomerulonephritis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Extracapillary Glomerulonephritis
Intervention  ICMJE Drug: Lisinopril
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Lisinopril
  • No Intervention: No intervention
    Patients will receive only the standard immunosuppressive therapy.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 12, 2016)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Barbara Ruggiero, MD 0039 035 45351 barbara.ruggiero@marionegri.it
Contact: Ettore Sabadini, MD esabadini@asst-pg23.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02682459
Other Study ID Numbers  ICMJE EXTRA
2015-003884-12 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Monia Lorini, A.O. Ospedale Papa Giovanni XXIII
Study Sponsor  ICMJE Monia Lorini
Collaborators  ICMJE Istituto Di Ricerche Farmacologiche Mario Negri
Investigators  ICMJE Not Provided
PRS Account A.O. Ospedale Papa Giovanni XXIII
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP