Treatment of IgA Nephropathy According to Renal Lesions

Assistance Publique - Hôpitaux de Paris62 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

IgA Nephropathy

Interventions

corticotherapyDRUG

3 IV pulses steroids followed by oral steroids for 4 months

Renin Angiotensin system (RAS) blockade or Inhibitors of sodium glucose transporter 2 (SGLT2i)DRUG

treatment with Renin angiotensin system (RAS) blockade or SGLT2i

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age \>= 18 years 2. Patient with IgAN 3. Renal biopsy \< 45 days before inclusion visit 4. PCR ratio \>0.75 g/g (within 30 days before or after the renal biopsy) 5. 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) 6. Patient with Social Security Insurance or CMU 7. Patient having signed an informed consent Exclusion Criteria: 1. \>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 2. \>50% cellular/fibrocellular crescents, or \>50% tubulointerstitial fibrosis or \>50% globally sclerotic glomeruli 3. Nephrotic syndrome with minimal change disease and IgA deposits 4. eGFR \<20 ml/min/1,73m2 (CKD-EPI formula) within 30 days before or after the renal biopsy 5. Uncontrolled blood pressure (Systolic blood pressure \>180 mmHg or diastolic blood pressure \> 110 mmHg) 6. Previous corticosteroids treatment (\>20 mg/d during more than 15 days, within the last 3 months before the renal biopsy) 7. Pregnancy or breast feeding or women without sufficient contraception 8. Secondary known forms of IgAN 9. Henoch-Schoenlein purpura 10. Additional other chronic renal disease 11. 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 12. Contraindication for RAS orSGLT2i blockade therapy 13. Known allergy or intolerance to corticoids or lactose 14. Organ transplant patient

Locations (1)

Hôpital Necker Enfants-malades

Paris, Paris, France

Outcomes

Primary Outcomes

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

Time frame: Month 24

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Data from ClinicalTrials.gov

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