NCT05946564

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
126

participants targeted

Target at P25-P50 for phase_3

Timeline
18mo left

Started Oct 2023

Typical duration for phase_3

Geographic Reach
1 country

24 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress63%
Oct 2023Oct 2027

First Submitted

Initial submission to the registry

June 6, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 14, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

October 24, 2023

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 24, 2027

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 24, 2027

Last Updated

May 16, 2025

Status Verified

May 1, 2025

Enrollment Period

3.5 years

First QC Date

June 6, 2023

Last Update Submit

May 14, 2025

Conditions

ANCA Associated VasculitisRapidly Progressive GlomerulonephritisCrescentic Glomerulonephritis

Keywords

ANCAvasculitis

Outcome Measures

Primary Outcomes (1)

  • Appearance of a success defined as (1) Delta sCreat > 30% (between D0 and week 26) AND (2) urine protein-to-creatinine (uPCR) < 1g/mmol

    Week 26

Secondary Outcomes (16)

  • Change of renal function

    Weeks 4, 12, 26 and 52

  • Proteinuria ratio

    Weeks 4, 12, 26 and 52

  • Score VDI (Vasculitis Damage Index)

    Week 26 and 52

  • Renal vasculitis activity

    Weeks 4, 12, 26 and 52

  • Renal vasculitis activity

    Weeks 4, 12, 26 and 52

  • +11 more secondary outcomes

Study Arms (2)

Pioglitazone (ACTOS®)

EXPERIMENTAL

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

Drug: Pioglitazone (ACTOS®)

Placebo of pioglitazone

PLACEBO COMPARATOR

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

Drug: Placebo of Pioglitazone

Interventions

Pioglitazone (ACTOS®)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.

Pioglitazone (ACTOS®)
Placebo of PioglitazoneDRUG

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.

Placebo of pioglitazone

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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)

You may not qualify if:

  • 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
  • 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
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

CHU Amiens

Amiens, 80000, France

RECRUITING

CHU d'Angers

Angers, 49933, France

RECRUITING

CH de Boulogne sur Mer

Boulogne-sur-Mer, 62200, France

RECRUITING

CHU Brest - Hôpital de la Cavale Blanche

Brest, 29200, France

RECRUITING

CHU de Dijon

Dijon, 21000, France

RECRUITING

CHU de Grenoble - Hôpital Michalon site nord

Grenoble, 38043, France

RECRUITING

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, 85925, France

RECRUITING

Hopital Le Kremlin Bicetre - Aphp

Le Kremlin-Bicêtre, 94270, France

RECRUITING

AP-HM - Hôpital la Conception

Marseille, 13005, France

RECRUITING

CHU de Nantes - Hotel Dieu

Nantes, 44093, France

RECRUITING

CHU Pasteur 2 - Nice

Nice, 06000, France

RECRUITING

CHU Nîmes - Hôpital universitaire Caremeau

Nîmes, 30009, France

RECRUITING

AP-HP - Hôpital Cochin

Paris, 75015, France

RECRUITING

AP-HP - Necker enfants malades

Paris, 75015, France

RECRUITING

HEGP

Paris, 75015, France

RECRUITING

AP-HP - Hôpital Bichat

Paris, 75018, France

RECRUITING

AP-HP - Tenon

Paris, 75020, France

RECRUITING

AP-HP - Henri Mondor

Paris, 94000, France

RECRUITING

CHU de Rouen

Rouen, 76000, France

RECRUITING

CHU de Strasbourg

Strasbourg, 67000, France

RECRUITING

CHU de Toulouse - Hôpital Rangueil

Toulouse, 31059, France

RECRUITING

CH Valenciennes

Valenciennes, 59300, France

RECRUITING

Chru de Nancy

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

Hôpital Robert Schuman (UNEOS)

Vantoux, 57070, France

NOT YET RECRUITING

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisVasculitis

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Systemic VasculitisVascular DiseasesCardiovascular DiseasesSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Alexandre Karras

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Maxime Brussieux

CONTACT

01 44 84 17 89maxime.brussieux@aphp.fr

Laura Le Mao

CONTACT

01 56 09 54 97laura.le-mao@aphp.fr

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double-blind (investigators and patients)
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 6, 2023

First Posted

July 14, 2023

Study Start

October 24, 2023

Primary Completion (Estimated)

April 24, 2027

Study Completion (Estimated)

October 24, 2027

Last Updated

May 16, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will share

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
Two years after the last publication
Access Criteria
Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).

Locations

FR(24)