Treatment of IgA Nephropathy According to Renal Lesions (TIGER)

October 31, 2022 updated by: Assistance Publique - Hôpitaux de Paris

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Paris, France, 75015
        • Hôpital Necker Enfants-Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CONTROL
Treatment with Renin Angiotensin system (RAS) blockade or SGLT2i.
treatment with Renin angiotensin system (RAS) blockade or SGLT2i
Experimental: EXPERIMENTAL
Corticotherapy + RAS blockade or SGLT2i treatment. Drug injection (intravenous) + tablets
treatment with Renin angiotensin system (RAS) blockade or SGLT2i
3 IV pulses steroids followed by oral steroids for 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure at 24 months
Time Frame: Month 24

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure at 6 months
Time Frame: Month 6

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
Failure at 12 months
Time Frame: Month 12

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
Proportion of patients with persistent severe histological lesions in repeat kidney biopsy at 12 months
Time Frame: Month 12
to compare the evolution of histological lesions between treatment groups at 12 months
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
Time Frame: Month 12
to compare the evolution of measured GFR (mGFR) between treatment groups at 12 months (or estimated GFR (eGFR) if unavailable)
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
Time Frame: Month 24
to compare the evolution of measured GFR (mGFR) between treatment groups at 24 months (or estimated GFR (eGFR) if unavailable)
Month 24
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
Time Frame: Month 12 and 24
to compare the evolution of proteinuria in each group
Month 12 and 24
SF36 scale at 12 months
Time Frame: Month 12
to compare the quality of life in each therapeutic group
Month 12
SF36 scale at 24 months
Time Frame: Month 24
to compare the quality of life in each therapeutic group
Month 24
Number of side effects
Time Frame: Month 24
to assess the tolerance of treatments in each therapeutic group
Month 24
Prognosis markers of failure at 24 months
Time Frame: Month 24
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dominique JOLY, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Principal Investigator: Eric ALAMARTINE, CHU Saint-etienne
  • Study Chair: Khalil El Karoui, Henri Mondor University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2018

Primary Completion (Actual)

February 20, 2022

Study Completion (Anticipated)

January 1, 2024

Study Registration Dates

First Submitted

May 2, 2017

First Submitted That Met QC Criteria

June 13, 2017

First Posted (Actual)

June 16, 2017

Study Record Updates

Last Update Posted (Actual)

November 3, 2022

Last Update Submitted That Met QC Criteria

October 31, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • P140931
  • 2016-004507-31 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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