Multicentre Prospective Open Label Clinical Study to Evaluate the Effect of Personalized Therapy on Patients With Immunoglobulin A Nephropathy.
Trial ID: NCT04662723
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE4
Start date: 2023-05-01
Completion date: 2028-12-31
Sponsor: Fondazione Schena
Collaborators: University of Bari
Conditions: Glomerulonephritis; Immunoglobulin A Nephropathy
Interventions: Corticosteroid; Renin-angiotensin sytem blockers; Sodium-glucose cotransporter 2 inhibitor
Locations: francesco paolo Schena; francesco paolo Schena
Countries: Italy; Italy
Enrollment: 878
Age range: 18 Years - None
Sex: ALL

Summary:
Idiopathic immunoglobulin A nephropathy (IgAN) is the most common biopsy-proven glomerulonephritis in the world. Approximately 40% of IgAN patients reach end-stage kidney disease (ESKD) 20 years after their kidney biopsy. The high prevalence of ESKD suggests the need to move from a generalized therapy for all patients to personalized therapy.

Many RCTs have been conducted stratifying patients based on the laboratory findings (serum creatinine, eGFR and daily proteinuria). In contrast, data from the kidney biopsy has been used only for clinical diagnosis. Therefore, IgAN patients with active or chronic renal lesions have not been equally distributed in experimental and control arms of the randomized clinical trials (RCTs) Our clinical study of IgAN (CLIgAN) is a multicentre, prospective, controlled and open-label randomized clinical trial based on patients' stratification at the time of their kidney biopsy. The investigators will consider, first, the type of renal lesions followed by the serum creatinine values, eGFR and proteinuria. IgAN patients with active renal lesions (n=132) will be enrolled in the first RCT (ACIgAN) in which they will receive corticosteroids (pulse therapy) plus oral corticosteroids combined with RASB or RASB followed by oral corticosteroids. IgAN patients with chronic or moderate renal lesions at high or very high risk of chronic renal disease (n=294) will be enrolled in the second RCT (CHRONIgAN) in which they will receive the SGLT2 inhibitor combined with RASB compared with RASB combined with oral corticosteroids. Using this approach, the investigators hypothesize that patients could receive personalized therapy based on renal lesions to ensure that the right drug gets to the right patient at the right time.

Recently, we developed a Clinical Decision Support System (CDSS) tool using artificial intelligence (artificial neural networks) to identify IgAN patients at high risk of developing ESKD. The IgAN tool (DialCheck) was validated in a retrospective cohort of IgAN patients but not in a prospective clinical study. The investigators propose to measure the power of the DiaCheck tool in patients enrolled in both RCTs to determine whether personalized therapy can slow the decline of the renal function to delay the ESKD.

The CLIgAN study also includes a cutting-edge molecular study for precision therapy (PRECIgAN).

Eligibility criteria:
Inclusion Criteria:

* Only adult patients (age 18-70 years) with biopsy-proven idiopathic IgAN.
* IgAN patients with active or chronic or moderate renal lesions

Exclusion Criteria

* Patients with idiopathic IgAN and nephrotic syndrome (minimal change disease at kidney biopsy)
* IgAN patients with hematuria and acute renal failure
* IgAN patients with rapidly progressive glomerulonephritis (extracapillary lesions in more than 50% of glomeruli)
* Patients with secondary IgAN (lupus nephritis, Schoenlein-Henoch purpura, liver cirrhosis)
* Any prior immunosuppressive therapy
* Superimposed IgAN in kidney transplant
* Severe liver diseases
* Infections
* Malignancies
* Pregnancy
* Patients with myocardial infarction or cerebrovascular stroke in the previous 6 months
* Uncontrolled diabetes
* Aseptic necrosis of any bone
* Other conditions that can be exacerbated by corticosteroids
* Previous adverse side effects to RASBs
* Previous adverse side effects to SGLT2is
* Patients with mild renal lesions (M0,E0,S0,T0,C0), minor urinary findings, proteinuria \< 0.5 g/day, normal GFR and normal blood pressure

Outcomes:
-Proteinuria reduction within 6 months in IgAN patients with active renal lesions; Proteinuria reduction within 6 months in IgAN patients with active renal lesions; Proteinuria reduction within 6 months in IgAN patients with active renal lesions; Proteinuria reduction within 6 months in IgAN patients with active renal lesions; Proteinuria reduction within 6 months in IgAN patients with active renal lesions; Proteinuria reduction within 6 months in IgAN patients with active renal lesions; Proteinuria reduction within 6 months in IgAN patients with chronic renal lesions; Proteinuria reduction within 6 months in IgAN patients with chronic renal lesions; Proteinuria reduction within 6 months in IgAN with chronic renal lesions; Proteinuria reduction within 6 months in IgAN patients with chronic renal lesions; Proteinuria reduction within 6 months in IgAN with chronic renal lesions; Proteinuria reduction within 6 months in IgAN with chronic renal lesions