Treatment of IgA Nephropathy According to Renal Lesions

IgA Nephropathy Clinical Trial

— TIGER  

Official title:

Treatment of IgA Nephropathy According to Renal Lesions

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03188887
• Other study ID #: P140931
• Secondary ID: 2016-004507-31
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 20, 2018
• Est. completion date: January 2024

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: January 2024
• Est. primary completion date: February 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

Drug:
• corticotherapy
3 IV pulses steroids followed by oral steroids for 4 months
• Renin Angiotensin system (RAS) blockade or Inhibitors of sodium glucose transporter 2 (SGLT2i)
treatment with Renin angiotensin system (RAS) blockade or SGLT2i

Locations

Country	Name	City	State
France	Hôpital Necker Enfants-malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	SF36 scale at 12 months	to compare the quality of life in each therapeutic group	Month 12
Secondary	SF36 scale at 24 months	to compare the quality of life in each therapeutic group	Month 24
Secondary	Number of side effects	to assess the tolerance of treatments in each therapeutic group	Month 24
Secondary	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