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Treatment of IgA Nephropathy According to Renal Lesions (TIGER)

Primary Purpose

IgA Nephropathy

Status

Active

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

corticotherapy

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

About this trial

This is an interventional treatment trial for IgA Nephropathy focused on measuring NIgA, Kidney biopsy, GFR, Corticotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hôpital Necker Enfants-malades

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

CONTROL

EXPERIMENTAL

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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)

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)

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

SF36 scale at 12 months

to compare the quality of life in each therapeutic group

SF36 scale at 24 months

to compare the quality of life in each therapeutic group

Number of side effects

to assess the tolerance of treatments in each therapeutic group

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.

Full Information

NCT ID

NCT03188887

First Posted

May 2, 2017

Last Updated

October 31, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT03188887

Brief Title

Treatment of IgA Nephropathy According to Renal Lesions

Acronym

TIGER

Official Title

Treatment of IgA Nephropathy According to Renal Lesions

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 20, 2018 (Actual)

Primary Completion Date

February 20, 2022 (Actual)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

IgA Nephropathy

Keywords

NIgA, Kidney biopsy, GFR, Corticotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CONTROL

Arm Type

Active Comparator

Arm Description

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

Arm Title

EXPERIMENTAL

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

corticotherapy

Intervention Description

3 IV pulses steroids followed by oral steroids for 4 months

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

treatment with Renin angiotensin system (RAS) blockade or SGLT2i

Primary Outcome Measure Information:

Title

Failure at 24 months

Description

Time Frame

Month 24

Secondary Outcome Measure Information:

Title

Failure at 6 months

Description

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

Title

Failure at 12 months

Description

Time Frame

Month 12

Title

Proportion of patients with persistent severe histological lesions in repeat kidney biopsy at 12 months

Description

to compare the evolution of histological lesions between treatment groups at 12 months

Time Frame

Month 12

Title

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

Description

to compare the evolution of measured GFR (mGFR) between treatment groups at 12 months (or estimated GFR (eGFR) if unavailable)

Time Frame

Month 12

Title

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

Description

to compare the evolution of measured GFR (mGFR) between treatment groups at 24 months (or estimated GFR (eGFR) if unavailable)

Time Frame

Month 24

Title

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

Description

to compare the evolution of proteinuria in each group

Time Frame

Month 12 and 24

Title

SF36 scale at 12 months

Description

to compare the quality of life in each therapeutic group

Time Frame

Month 12

Title

SF36 scale at 24 months

Description

to compare the quality of life in each therapeutic group

Time Frame

Month 24

Title

Number of side effects

Description

to assess the tolerance of treatments in each therapeutic group

Time Frame

Month 24

Title

Prognosis markers of failure at 24 months

Description

Clinical, histological, and biological data (including PCR ratio, eGFR and mGFR, renal histological lesions) will be compared between patients with or without failure.

Time Frame

Month 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dominique JOLY, MD, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Eric ALAMARTINE

Organizational Affiliation

CHU Saint-Etienne

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Khalil El Karoui

Organizational Affiliation

Henri Mondor University Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Hôpital Necker Enfants-malades

City

Paris

ZIP/Postal Code

75015

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Treatment of IgA Nephropathy According to Renal Lesions

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