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.
After a patient has consented to participate to the study, the informed consent form will be signed by the patient and the investigator. The patient will be randomized to one of two groups (pioglitazone or placebo). The patient will take the experimental treatment for 26 weeks and his research follow-up will last 52 weeks (follow-up visit : W1, W2, W3, W4 (research visit), W8, W12, W26, W38 and W52). All participants will receive SOC immunosuppressive treatment with rituximab at 375 mg/m2/week for 4 consecutive weeks, as induction therapy of vasculitis flare, followed by 500 mg re-infusion every 6 months/24 weeks as maintenance therapy, i.e. at week 26 and 52, as recommended. The two treatment groups will also receive a standardized glucocorticoid tapering schedule: one to three i.v. pulses of methylprednisolone (7.5 to 15 mg/kg each) according to physician decision, followed by a predefined oral prednisone tapering schedule as used in the reduced-dose arm of the PEXIVAS trial. Samples (plasma, serum and urine) taken as part of the study will be stored in a biological sample collection (at D0, W1, W2, W3, W12, W26, W38 and W52 visits).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
126
Patient 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.
Patient 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.
CHU Amiens
Amiens, France
RECRUITINGCHU d'Angers
Angers, France
RECRUITINGCH de Boulogne sur Mer
Boulogne-sur-Mer, France
RECRUITINGCHU Brest - Hôpital de la Cavale Blanche
Brest, France
RECRUITINGCHU de Dijon
Dijon, France
RECRUITINGCHU de Grenoble - Hôpital Michalon site nord
Grenoble, France
RECRUITINGCentre Hospitalier Départemental Vendée
La Roche-sur-Yon, France
RECRUITINGHopital Le Kremlin Bicetre - Aphp
Le Kremlin-Bicêtre, France
RECRUITINGAP-HM - Hôpital la Conception
Marseille, France
RECRUITINGCHU de Nantes - Hotel Dieu
Nantes, France
RECRUITING...and 14 more locations
Appearance of a success defined as (1) Delta sCreat > 30% (between D0 and week 26) AND (2) urine protein-to-creatinine (uPCR) < 1g/mmol
Time frame: Week 26
Change of renal function
Delta sCreat (baseline sCreat - follow-up sCreat)
Time frame: Weeks 4, 12, 26 and 52
Proteinuria ratio
Spot urine protein-to-creatinine ratio (uPCR)
Time frame: Weeks 4, 12, 26 and 52
Score VDI (Vasculitis Damage Index)
Systemic chronic damage due to vasculitis and treatment of vasculitis Min : 0 Max : 62 the best score is 0
Time frame: Week 26 and 52
Renal vasculitis activity
measurement of urine biomarkers: MCP-1
Time frame: Weeks 4, 12, 26 and 52
Renal vasculitis activity
measurement of urine biomarkers: KIM-1
Time frame: Weeks 4, 12, 26 and 52
Renal vasculitis activity
measurement of urine biomarkers: Calprotectin
Time frame: Weeks 4, 12, 26 and 52
Renal vasculitis activity
measurement of urine biomarkers: CD163
Time frame: Weeks 4, 12, 26 and 52
Systemic vasculitis activity : score BVAS
BVAS (Birmingham Vasculitis Activity Score ), ANCA positivity Min : 0 Max : 63 The best score is 0
Time frame: Weeks 4, 12, 26 and 52
Refractory vasculitis
Percentage of patients with refractory vasculitis and early vasculitis relapses
Time frame: Weeks 12, 26 and 52
Improvement in Quality of Life (SF-36)
SF-36 : Short-form 36 Min : 0 Max : 100 A low score reflects a perception of poor health, loss of function, presence of pain. A high score reflects a perception of good health, an absence of functional deficit and pain.
Time frame: baseline, weeks 4, 12, 26 and 52
Improvement in Quality of Life (EQ-5D)
EQ-5D : Euroqol Min: 0 Max : 100 Higher scores mean a better
Time frame: baseline, weeks 4, 12, 26 and 52
Safety profile of pioglitazone
numbers of adverse events, numbers of patients with adverse events, numbers of serious adverse events
Time frame: Weeks 26 and 52
Toxicity induced by glucocorticoids
Glucocorticoid Toxicity Index (GTI) the best score is 0
Time frame: Weeks 12, 26 and 52
Change metabolic effects of Glucocorticoids
To assess the efficacy of pioglitazone on the reduction metabolic side effects of glucocorticoids by HbA1c
Time frame: Weeks 12, 26 and 52.
Change metabolic effects of Glucocorticoids
To assess the efficacy of pioglitazone on the reduction metabolic side effects of glucocorticoids by evaluation of lipid profile
Time frame: Weeks 12, 26 and 52.
Change blood pressure
To assess the efficacy of pioglitazone on the reduction of hypertension)
Time frame: Weeks 12 and 26.
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