Clinical trial NCT03188887: Treatment of IgA Nephropathy According to Renal Lesions
Official title: Treatment of IgA Nephropathy According to Renal Lesions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: IgA Nephropathy
Keywords: NIgA
Kidney biopsy
GFR
Corticotherapy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-06-16
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Failure at 24 months
timeFrame: Month 24
Secondary outcomes:
measure: Failure at 6 months
timeFrame: Month 6
measure: Failure at 12 months
timeFrame: Month 12
measure: Proportion of patients with persistent severe histological lesions in repeat kidney biopsy at 12 months
timeFrame: Month 12
measure: 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
timeFrame: Month 12
measure: 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
timeFrame: Month 24
measure: 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
timeFrame: Month 12 and 24
measure: SF36 scale at 12 months
timeFrame: Month 12
measure: SF36 scale at 24 months
timeFrame: Month 24
measure: Number of side effects
timeFrame: Month 24
measure: Prognosis markers of failure at 24 months
timeFrame: Month 24
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker Enfants-malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Dominique JOLY, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU SAINT-ETIENNE
name: Eric ALAMARTINE
role: PRINCIPAL_INVESTIGATOR
affiliation: Henri Mondor University Hospital
name: Khalil El Karoui
role: STUDY_CHAIR
References: