Treatment of IgA Nephropathy According to Renal Lesions

Study Overview
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Brief Summary
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TIGER study (Treatment of IgA nEphropathy according to Renal lesions) is a prospective openly randomized controlled study. The main objective is to evaluate the efficacy of early corticotherapy + Renin Angiotensin System (RAS) blockade or inhibitors of Sodium glucose transporter 2 (SGLT2i) (versus RAS blockade or SGLT2i alone) after two years of evolution in IgAN patients with severe histological lesions.

Detailed Description
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Currently, IgAN treatment recommendations are only based on clinico-biological parameters. Steroids therapy appears to have a major role in IgAN treatment, but previous studies evaluating steroids lacked of optimal control group and reproducible evaluation criteria. No prospective study with optimal nephroprotection had included renal pathology in patients selection criteria, although histological evaluation improves patients prognosis prediction. Until now, the lack of a reliable histological classification has precluded the use of histological lesions to evaluate IgAN prognosis and treatment. Given the recently identified major prognostic role of histological lesions in IgAN, we propose to introduce renal pathology to guide the treatment of IgAN in a multicenter study, using currently validated evaluation criteria of chronic kidney disease progression.

Official Title
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Treatment of IgA Nephropathy According to Renal Lesions

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: corticotherapy
* Drug: Renin Angiotensin system (RAS) blockade or Inhibitors of sodium glucose transporter 2 (SGLT2i)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Patient with IgAN Renal biopsy < 45 days before inclusion visit PCR ratio >0.75 g/g (within 30 days before or after the renal biopsy) Renal biopsy with at least 8 glomeruli, disclosing at least 2 criteria among: mesangial proliferation (according to Oxford criteria) endocapillary proliferation (according to Oxford criteria) tubulointerstitial fibrosis (according to Oxford criteria) >25% of the biopsy segmental glomerulosclerosis (according to Oxford criteria) at least 1 cellular/fibrocellular crescents (C1 according to Oxford criteria) Patient with Social Security Insurance or CMU Patient having signed an informed consent Exclusion Criteria: >30% increase of serum creatinine after starting nephroprotection therapy (≥ 15 days and ≤ 6 weeks) only for patient under nephroprotection <45 days of the inclusion visit >50% cellular/fibrocellular crescents, or >50% tubulointerstitial fibrosis or >50% globally sclerotic glomeruli Nephrotic syndrome with minimal change disease and IgA deposits eGFR <20 ml/min/1,73m2 (CKD-EPI formula) within 30 days before or after the renal biopsy Uncontrolled blood pressure (Systolic blood pressure >180 mmHg or diastolic blood pressure > 110 mmHg) Previous corticosteroids treatment (>20 mg/d during more than 15 days, within the last 3 months before the renal biopsy) Pregnancy or breast feeding or women without sufficient contraception Secondary known forms of IgAN Henoch-Schoenlein purpura Additional other chronic renal disease Contraindication for immunosuppressive therapy, including active intestinal bleeding, active gastric or duodenal ulcer; active infection; any malignancy in a last years before the inclusion; severe psychiatric disease; living vaccines; anti-inflammatory dosages of acetylsalicylic acid Contraindication for RAS orSGLT2i blockade therapy Known allergy or intolerance to corticoids or lactose Organ transplant patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CONTROL<br>Treatment with Renin Angiotensin system (RAS) blockade or SGLT2i. | Drug: Renin Angiotensin system (RAS) blockade or Inhibitors of sodium glucose transporter 2 (SGLT2i)<br>* treatment with Renin angiotensin system (RAS) blockade or SGLT2i<br>|
| Experimental: EXPERIMENTAL<br>Corticotherapy + RAS blockade or SGLT2i treatment. Drug injection (intravenous) + tablets | Drug: corticotherapy<br>* 3 IV pulses steroids followed by oral steroids for 4 months<br>Drug: Renin Angiotensin system (RAS) blockade or Inhibitors of sodium glucose transporter 2 (SGLT2i)<br>* treatment with Renin angiotensin system (RAS) blockade or SGLT2i<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure at 24 months | Failure at 24 months will be defined as : Proteinuria/creatinuria ratio (PCR) > 0,5 g/g or mGFR < 80% of initial mGFR (or eGFR if unavailable) or loss of more than 10 ml/min/1,73m2 of initial mGFR (or eGFR if unavailable) or end stage renal disease (ESRD) or renal transplantation or death | Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure at 6 months | Failure at 6 months will be defined as: PCR > 0.75 g/g or PCR > 0.5 g/g and >30% of initial PCR or eGFR < 80% of initial eGFR or end stage renal disease (ESRD) or renal transplantation or death | Month 6 | 
| Failure at 12 months | Failure at 12 months will be defined as: PCR > 0.75 g/g or PCR > 0.5 g/g and > 30% of initial PCR or mGFR < 80% of initial mGFR (or eGFR if unavailable) or end stage renal disease (ESRD) or renal transplantation or death | Month 12 | 
| Proportion of patients with persistent severe histological lesions in repeat kidney biopsy at 12 months | to compare the evolution of histological lesions between treatment groups at 12 months | Month 12 | 
| Evolution of GFR at 12 months assessed as :- the absolute value of GFR - the absolute difference of GFR from the baseline - the annual degradation (ml/min /1,73m2/year) of GFR during the 12 months | to compare the evolution of measured GFR (mGFR) between treatment groups at 12 months (or estimated GFR (eGFR) if unavailable) | Month 12 | 
| Evolution of GFR at 24 months assessed as :- the absolute value of GFR - the absolute difference of GFR from the baseline - the annual degradation (ml/min /1,73m2/year) of GFR during the 24 months | to compare the evolution of measured GFR (mGFR) between treatment groups at 24 months (or estimated GFR (eGFR) if unavailable) | Month 24 | 
| Evolution of proteinuria assessed as : - the absolute value of proteinuria at 12 and 24 months - the absolute difference of proteinuria from baseline at 12 and 24 months | to compare the evolution of proteinuria in each group | Month 12 and 24 | 
| SF36 scale at 12 months | to compare the quality of life in each therapeutic group | Month 12 | 
| SF36 scale at 24 months | to compare the quality of life in each therapeutic group | Month 24 | 
| Number of side effects | to assess the tolerance of treatments in each therapeutic group | Month 24 | 
| Prognosis markers of failure at 24 months | Clinical, histological, and biological data (including PCR ratio, eGFR and mGFR, renal histological lesions) will be compared between patients with or without failure. | Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney biopsy, GFR, Corticotherapy, NIgA