Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05946564
Other study ID # APHP211045
Secondary ID 2022-501057-36-0
Status Not yet recruiting
Phase Phase 3
First received
Last updated
Start date July 2023
Est. completion date June 2, 2027

Study information

Verified date June 2023
Source Assistance Publique - Hôpitaux de Paris
Contact Ophélie Rogier
Phone 01 44 84 17 89
Email ophelie.rogier@aphp.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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).


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 126
Est. completion date June 2, 2027
Est. primary completion date December 2, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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 HCV 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 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 - 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)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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.
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.

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris Ministry of Health, France

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Change of renal function Delta sCreat (baseline sCreat - follow-up sCreat) Weeks 4, 12, 26 and 52
Secondary Proteinuria ratio Spot urine protein-to-creatinine ratio (uPCR) Weeks 4, 12, 26 and 52
Secondary Score VDI (Vasculitis Damage Index) Systemic chronic damage due to vasculitis and treatment of vasculitis Min : 0 Max : 62 the best score is 0 Week 26 and 52
Secondary Renal vasculitis activity measurement of urine biomarkers: MCP-1 Weeks 4, 12, 26 and 52
Secondary Renal vasculitis activity measurement of urine biomarkers: KIM-1 Weeks 4, 12, 26 and 52
Secondary Renal vasculitis activity measurement of urine biomarkers: Calprotectin Weeks 4, 12, 26 and 52
Secondary Renal vasculitis activity measurement of urine biomarkers: CD163 Weeks 4, 12, 26 and 52
Secondary Systemic vasculitis activity : score BVAS BVAS (Birmingham Vasculitis Activity Score ), ANCA positivity Min : 0 Max : 63 The best score is 0 Weeks 4, 12, 26 and 52
Secondary Refractory vasculitis Percentage of patients with refractory vasculitis and early vasculitis relapses Weeks 12, 26 and 52
Secondary 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. baseline, weeks 4, 12, 26 and 52
Secondary Improvement in Quality of Life (EQ-5D) EQ-5D : Euroqol Min: 0 Max : 100 Higher scores mean a better baseline, weeks 4, 12, 26 and 52
Secondary Safety profile of pioglitazone numbers of adverse events, numbers of patients with adverse events, numbers of serious adverse events Weeks 26 and 52
Secondary Toxicity induced by glucocorticoids Glucocorticoid Toxicity Index (GTI) the best score is 0 Weeks 12, 26 and 52
Secondary Change metabolic effects of Glucocorticoids To assess the efficacy of pioglitazone on the reduction metabolic side effects of glucocorticoids by HbA1c Weeks 12, 26 and 52.
Secondary Change metabolic effects of Glucocorticoids To assess the efficacy of pioglitazone on the reduction metabolic side effects of glucocorticoids by evaluation of lipid profile Weeks 12, 26 and 52.
Secondary Change blood pressure To assess the efficacy of pioglitazone on the reduction of hypertension) Weeks 12 and 26.
See also
  Status Clinical Trial Phase
Recruiting NCT06462768 - Neutrophil Extracellular Traps in Different Forms of Systemic Sclerosis
Recruiting NCT03942887 - Exploring Durable Remission With Rituximab in Antineutrophil Cytoplasmic Antibody(ANCA)-Associated Vasculitis Phase 3
Not yet recruiting NCT06420154 - The Safety and Efficacy of Anti-CD19 CAR-T Cells in Patients With Relapsed/Refractory Autoimmune Diseases Early Phase 1
Completed NCT04895878 - Patients With Co-occurrence of ANCA Vasculitis and Sjögren Syndrome
Completed NCT00293072 - Pilot Study of Rituximab Therapy for Systemic Lupus Erythematosus (SLE) and Vasculitis Phase 2
Recruiting NCT04664465 - PRediction Of DIverse Glucocorticoids toxIcity OUtcomeS
Recruiting NCT05315141 - Multicenter Cohort Study of AAV in Hunan of China
Terminated NCT05376319 - PR3-AAV Resilient Remission or PRRR Phase 2
Recruiting NCT04737343 - Comparison of the Efficacy of Leflunomide and Azathioprine for the Maintenance Therapy of ANCA Associated Vasculitis N/A
Recruiting NCT05962840 - Efficacy and Safety for Rituximab Combined With Telitacicept in the Treatment of ANCA-associated Vasculitis (TTCAAVREM) Phase 4
Suspended NCT03906227 - Tailoring Maintenance Therapy to Cluster of Differentiation 5 Positive (CD5+) Regulatory B Cell Recovery in ANCA Vasculitis N/A
Not yet recruiting NCT06152172 - CARTIMMUNE: Study of Patients With Autoimmune Diseases Receiving KYV-101 Phase 1
Recruiting NCT04923074 - the Application of Diffusion Tensor Imaging in the Evaluation of Peripheral Neuropathy in ANCA Associated Vasculitis
Active, not recruiting NCT01633476 - CMV Modulation of the Immune System in ANCA-associated Vasculitis Phase 2
Not yet recruiting NCT05416723 - Occupational and Environmental Origins of ANCA Vasculitis: Contribution of Data From the National Network for Vigilance and Prevention of Occupational Pathologies (RNV3P)
Recruiting NCT06277427 - Refractory ANCA Associated Vasculitis and Lupus Nephritis Treated With BCMA-targeting CAR-T Cells N/A
Active, not recruiting NCT03967925 - Rituximab and Belimumab Combination Therapy in PR3 Vasculitis Phase 2
Recruiting NCT05630612 - ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC) Phase 2
Recruiting NCT04316494 - Hydroxychloroquine in ANCA Vasculitis Evaluation Phase 4
Recruiting NCT03698071 - Soluble CD95 Ligand Role in the Pathophysiology of Antineutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis N/A