A Trial to Evaluate the Efficacy of Pioglitazone to Promote Renal Tolerance in ANCA-associated Vasculitis - RENATO Trial

NCT ID: NCT05946564

Last Updated: 2025-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-24

Study Completion Date

2027-10-24

Brief Summary

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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.

Detailed Description

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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).

Conditions

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ANCA Associated Vasculitis Rapidly Progressive Glomerulonephritis Crescentic Glomerulonephritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Comparative, multicentre, prospective, randomized, placebo-controlled double-blind phase III trial, evaluating the efficacy of add-on pioglitazone therapy on top of a standard of care (SOC) immunosuppressive therapy, in patients with ANCA-associated vasculitis and biopsy-proven renal involvement. Patients eligible for the study will be assigned in a 1:1 randomized fashion to additional treatment by pioglitazone (30 mg/day orally) or to placebo for 26 weeks on top of a SOC immunosuppressive treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Double-blind (investigators and patients)

Study Groups

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Pioglitazone (ACTOS®)

Pioglitazone given once a day, orally, at 30 mg dose, for 26 weeks

Group Type EXPERIMENTAL

Pioglitazone (ACTOS®)

Intervention Type DRUG

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.

Placebo of pioglitazone

Placebo of pioglitazone, given once a day, orally, for 26 weeks

Group Type PLACEBO_COMPARATOR

Placebo of Pioglitazone

Intervention Type DRUG

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.

Interventions

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Pioglitazone (ACTOS®)

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.

Intervention Type DRUG

Placebo of Pioglitazone

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
* Participant written informed consent prior to participation in the study
* Participants affiliated to a French health insurance system (registered or being a beneficiary of such a scheme)

Exclusion Criteria

* 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
* Past history of bladder or urinary tract cancer
* History of Class 3/4 congestive heart failure symptoms, any time
* History of Class 2 heart failure symptoms within the past 3 months and/or ejection fraction \<40% on recent echocardiography (\<1 month)
* Transaminases levels above 2 times the normal range value (\<1 month) or any severe chronic liver disease
* Positive serology for HIV, HBV (Ag HBs positivity) or active HCV infection at inclusion
* Presence of neutropenia \<1000 cells/l (\<1 month)
* History of intolerance to any thiazolidinedione (including Pioglitazone), to rituximab or any excipient listed in SmPc
* Diabetic ketoacidosis, any time
* A pre-existing or an important risk of new-onset macular edema (confirmed by an ophthalmological examination)
* Pregnant or breast-feeding women, or desire to become pregnant within 24 months All women of childbearing potential (WOCBP) are required to have a negative pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using an effective method of birth control from the date of consent through the end of the study and another 12 months after (or 12 months after the last rituximab infusion in case of premature termination): Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (Oral, Intravaginal, Transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (Oral, Injectable, Implantable); Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised partner
* Severe neurologic or psychiatric disease (e.g., dementia or schizophrenia)
* Kidney transplant recipients
* Cyclophosphamide or rituximab (dose \> 375 mg/m2) use within 26 weeks prior to screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the first rituximab dose. Patients that have initiated induction therapy with rituximab for the actual flare, can be included in the present study within 48h following the first rituximab infusion
* Intravenous glucocorticoids, \>3000 mg methylprednisolone equivalent, within 4 weeks prior to screening
* Patients who have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening
* Current participation in another research study involving a therapeutic intervention. Participation to an observational research, or a non-interventional research is allowed
* Patients under guardianship or curators and protected adults
* Patients not able to understand and follow study procedures
* Patients on AME (Aide Médicale de l'Etat = State Medical Assistance)
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexandre Karras

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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CHU Amiens

Amiens, , France

Site Status RECRUITING

CHU d'Angers

Angers, , France

Site Status RECRUITING

CH de Boulogne sur Mer

Boulogne-sur-Mer, , France

Site Status RECRUITING

CHU Brest - Hôpital de la Cavale Blanche

Brest, , France

Site Status RECRUITING

CHU de Dijon

Dijon, , France

Site Status RECRUITING

CHU de Grenoble - Hôpital Michalon site nord

Grenoble, , France

Site Status RECRUITING

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, , France

Site Status RECRUITING

Hopital Le Kremlin Bicetre - Aphp

Le Kremlin-Bicêtre, , France

Site Status RECRUITING

AP-HM - Hôpital la Conception

Marseille, , France

Site Status RECRUITING

CHU de Nantes - Hotel Dieu

Nantes, , France

Site Status RECRUITING

CHU Pasteur 2 - Nice

Nice, , France

Site Status RECRUITING

CHU Nîmes - Hôpital universitaire Caremeau

Nîmes, , France

Site Status RECRUITING

AP-HP - Hôpital Cochin

Paris, , France

Site Status RECRUITING

AP-HP - Necker enfants malades

Paris, , France

Site Status RECRUITING

HEGP

Paris, , France

Site Status RECRUITING

AP-HP - Hôpital Bichat

Paris, , France

Site Status RECRUITING

AP-HP - Tenon

Paris, , France

Site Status RECRUITING

AP-HP - Henri Mondor

Paris, , France

Site Status RECRUITING

CHU de Rouen

Rouen, , France

Site Status RECRUITING

CHU de Strasbourg

Strasbourg, , France

Site Status RECRUITING

CHU de Toulouse - Hôpital Rangueil

Toulouse, , France

Site Status RECRUITING

CH Valenciennes

Valenciennes, , France

Site Status RECRUITING

Chru de Nancy

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Hôpital Robert Schuman (UNEOS)

Vantoux, , France

Site Status NOT_YET_RECRUITING

Countries

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France

Central Contacts

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Maxime Brussieux

Role: CONTACT

01 44 84 17 89

Laura Le Mao

Role: CONTACT

01 56 09 54 97

Facility Contacts

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Dimitri TITECA-BEAUPORT

Role: primary

Jean-François AUGUSTO

Role: primary

02 41 35 39 34

Rafik Mesbah

Role: primary

Emilie Cornec-Legall

Role: primary

Maxime Samson

Role: primary

Pierre-Louis Carron

Role: primary

Grégoire COUVRAT-DESVERGNES

Role: primary

Julien Dang

Role: primary

Noémie Jourde-Chiche

Role: primary

Antoine Neel

Role: primary

Clément GOSSET

Role: primary

04 92 03 77 77

Olivier Moranne

Role: primary

Benjamin Terrier

Role: primary

Aurélie Hummel

Role: primary

Alexandre Karras

Role: primary

Eric Daugas

Role: primary

Jean-Jacques Boffa

Role: primary

Vincent Audard

Role: primary

Tristan De Nattes

Role: primary

Anna DUVAL

Role: primary

03 69 55 00 65

Stanislas Faguer

Role: primary

Thomas Quemeneur

Role: primary

Adrien Flahault

Role: primary

Julien Campagne

Role: primary

Other Identifiers

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2022-501057-36-00

Identifier Type: OTHER

Identifier Source: secondary_id

PHRC-20-0707

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

APHP211045

Identifier Type: -

Identifier Source: org_study_id

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