EXTRA: ACE-inhibitors in Extracapillary Glomerulonephritis

Sponsor

Monia Lorini (Other)

Overall Status

Unknown status

CT.gov ID

NCT02682459

Collaborator

Istituto Di Ricerche Farmacologiche Mario Negri (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Feb 1, 2016

Anticipated Primary Completion Date :

Sep 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 [Changes from baseline and 6 and 18 month.]
Number of fibrosclerotic crescents [Changes from baseline and 6 and 18 month.]
Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance [Changes from baseline and 6, 12 and 18 month.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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:

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 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.