The RENATO trial is a multicenter randomized controlled trial that evaluates the efficacy of pioglitazone to improve renal outcomes in ANCA-associated vasculitis.
Patients with biopsy-proven kidney involvement of ANCA vasculitis will be included in this trial at diagnosis. All patients will receive a standard of care immunosuppressive (SOC) therapy combining corticosteroids and rituximab (375 mg/m2/week for 4 consecutive weals followed by 500 mg re-infusion every 6 months). They will be randomized 1:1 to receive either pioglitazone 30 mg/day or placebo for 6 months, on top of SOC. The primary objective of this trial is to demonstrate that pioglitazone reduces kidney damage, reflected by the early improvement of proteinuria and serum creatinine levels. The secondary objectives will be to assess the efficacy of this drug on the reduction of hypertension and metabolic effects of glucocorticoids, to measure its impact on vasculitis activity and to evaluate the safety profile of pioglitazone in this population.
Newly-diagnosed or relapsing ANCA-associated vasculitis, i.e. granulomatosis with polyangitis (GPA) or microscopic polyangiitis (MPA), according to ACR 1990 criteria and/or revised Chapel Hill Consensus Conference definitions and/or European Medical Agency algorithm, with an active disease defined as a BVAS ≥3
Presence of proteinuria (UPCR >300 mg/g), haematuria (>10 RBC/hpf), and eGFR ≥15 mL/min/1.73 m2 (CKD-EPI formula) at inclusion (<1 month)
Recent (<4 weeks) renal biopsy that confirms active renal involvement of ANCA-associated vasculitis
Patients aged of 18 to 80 years
Alveolar haemorrhage requiring pulmonary ventilation support at inclusion
Patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss)
Active cancer (except non-melanoma skin cancer) within the past 24 months
Active severe bacterial, viral or fungal infectious disease
Parallel
Pioglitazone (ACTOS®)
DrugPatient will be randomize in the intervention group receive treatment by pioglitazone (30 mg/day orally) for 26 weeks on top of a SOC immunosuppressive treatment.
Placebo of Pioglitazone
DrugPatient will be randomize in the intervention group receive treatment by placebo of pioglitazone (30 mg/day orally) for 26 weeks on top of a SOC immunosuppressive treatment.
Appearance of a success defined as (1) Delta sCreat > 30% (between D0 and week 26) AND (2) urine protein-to-creatinine (uPCR) < 1g/mmol
Change of renal function
Delta sCreat (baseline sCreat - follow-up sCreat)
Proteinuria ratio
Spot urine protein-to-creatinine ratio (uPCR)
Score VDI (Vasculitis Damage Index)
Systemic chronic damage due to vasculitis and treatment of vasculitis Min : 0 Max : 62 the best score is 0
Renal vasculitis activity
measurement of urine biomarkers: MCP-1
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
Ministry of Health, France
Collaborator
