Treatment of IgA Nephropathy According to Renal Lesions (TIGER)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: IgA Nephropathy

Treatments: Drug: corticotherapy; Drug: Renin Angiotensin system (RAS) blockade or Inhibitors of sodium glucose transporter 2 (SGLT2i)

Study type: Interventional

Funder types: Other

Identifiers

NCT03188887

2016-004507-31 (EudraCT Number)

P140931

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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62 participants in 2 patient groups

CONTROL

Active Comparator group

Description:

Treatment with Renin Angiotensin system (RAS) blockade or SGLT2i.

Treatment:

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

EXPERIMENTAL

Experimental group

Description:

Corticotherapy + RAS blockade or SGLT2i treatment. Drug injection (intravenous) + tablets

Treatment:

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

Drug: corticotherapy