2022-501057-36-00招募中3 期
A multicenter randomized trial to evaluate the efficacy of pioglitazone to promote renal tolerance in ANCA-associated vasculitis - RENATO
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 19
- 主要终点
- Improvement of serum creatinine (Delta sCreat) >30% of inclusion value (if initial sCreat is >135 µmol/L) AND urine proteine-to-creatinine (uPCR) <1g/g, at week 26. A pre-specified subgroup analysis will be performed in patients according to age, renal pathology, initial renal function, de novo vs relapsing vasculitis and ANCA specificity.
研究概览
简要总结
To demonstrate a reduction of renal damage (reflected by the early improvement of proteinuria and serum creatinine), in ANCA-associated renal vasculitis, by pioglitazone add-on treatment on top of Standard Of Care (SOC) standardized immunosuppressive regimen with glucocorticoids and rituximab, after six months
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Newly-diagnosed or relapsing ANCA-associated vasculitis, i.e. granulomatosis with polyangiitis (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 vasculitis 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 (<1month)
- •Recent (<4 weeks) renal biopsy that confirms 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)
排除标准
- •Alveolar haemorrhage requiring pulmonary ventilation support at inclusion
- •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 with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss
- •Patients under guardianship or curatorship and protected adults
- •Patients not able to understand and follow study procedures
- •Patients on AME (Aide Médicale de l’Etat = State Medical Assistance)
- •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
- •Presence of neutropenia <1000 cells/µl (<1 month)
- •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
- •A pre-existing or an important risk of new-onset macular edema (confirmed by an ophthalmological examination)
- •History of intolerance to any thiazolidinedione (including Pioglitazone), to rituximab or any excipient listed in SmPc
- •Diabetic ketoacidosis, any time
- •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
结局指标
主要结局
Improvement of serum creatinine (Delta sCreat) >30% of inclusion value (if initial sCreat is >135 µmol/L) AND urine proteine-to-creatinine (uPCR) <1g/g, at week 26. A pre-specified subgroup analysis will be performed in patients according to age, renal pathology, initial renal function, de novo vs relapsing vasculitis and ANCA specificity.
Improvement of serum creatinine (Delta sCreat) >30% of inclusion value (if initial sCreat is >135 µmol/L) AND urine proteine-to-creatinine (uPCR) <1g/g, at week 26. A pre-specified subgroup analysis will be performed in patients according to age, renal pathology, initial renal function, de novo vs relapsing vasculitis and ANCA specificity.
次要结局
- Improvement of renal function (Delta sCreat, eGFR), renal survival and proteinuria at weeks 4, 12, 26, 52: -Renal function evaluated by Delta sCreat (sCreat at inclusion-sCreat follow-up), sCreat slopes, eGFR modifications (CKD-Epi formula); -Renal survival evaluated as the % of patients still alive and not requiring chronic dialysis therapy; -Proteinuria measured by spot uPCR; -Reduction of systemic chronic damage due to vasculitis; -Vasculitis-associated damage assessed by VDI at weeks 26 & 52
- Reduction of vasculitis activity at weeks 4, 12, 26, 52: -Residual activity of renal vasculitis evaluated by urine biomarkersme asurement: microhematuria, levels of urinary MCP-1, KIM-1, Calprotectin, CD163; -Systemic vasculitis activity assessed by the BVAS and by ANCA positivity; Percentage of patients with refractory vasculitis resistance and early vasculitis relapse at weeks 12, 26 & 52
- Improvement of Quality of Life during follow-up, measured by Short Form-36 component and domain scores and the EQ-5D-5L visual analogue scale and index at week 4, 12, 26, 52
- Safety of pioglitazone by evaluation of numbers of adverse events, number of patients with adverse events, numbers of serious adverse events, patient survival, at weeks 26 & 52. In addition, cardiac and liver toxicity of pioglitazone will be evaluated by assessment of plasma BNP and liver enzymes
- Reduction of glucocorticoid-induced toxicity during follow-up: -Glucocorticoid-induced toxicity measured by GTI at weeks 12, 26 & 52 -Metabolic effects of glucocorticoids will be evaluated by HbA1c levels & evaluation of lipid profile (Total, HDL and LDL cholesterol, triglycerides) at weeks 12, 26 & 52; Reduction of nephropathy-induced hypertension and numbers of antihypertensive drugs given during follow-up; -Hypertension evaluated by office measurement at each study visit & AMBP at weeks 12&26
研究者
Alexandre KARRAS
Scientific
Assistance Publique Hopitaux De Paris
研究点 (19)
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