A Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Artesunate Plus Standard of Care in Active Lupus Nephritis: Pilot Study
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Remission
研究概览
简要总结
This is a multi-center, randomized, double-blind, placebo-controlled study. Study subjects are class III, IV, V, III+V, IV+V lupus nephritis patients, according to ISN/RPS 2003 classification of LN, with active lesion needing corticosteroid in combination with immunosuppressant therapy.
Subjects who meet the eligibility criteria during screening will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio: 25mg bid artesunate, 50mg bid artesunate or placebo plus standard of care (prednisone plus mycophenolate mofetil ［MMF］) for 6 month.
详细描述
Lupus nephritis (LN) can be observed in up to 70% of SLE patients and is often associated with a poor long-term prognosis. Artesunate, one analogues of antimalarial agent artemisinin, have immunomodulatory properties that might be useful for treating autoimmune diseases including SLE. it is still lack of solid evidence from RCT to evaluate efficacy and safety of artesunate plus standard of care in active LN. Regarding no data could be referred to decide the sample size and optimal dosage, we designed this pilot study. The result and experience of pilot study will answer these questions, and guarantee the multicenter RCT to be conducted successfully.
This is a multi-center, randomized, double-blind, placebo-controlled study. Study subjects are class III, IV, V, III+V, IV+V lupus nephritis patients, according to ISN/RPS 2003 classification of LN, with active lesion needing corticosteroid in combination with immunosuppressant therapy.
Subjects who meet the eligibility criteria during screening will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio: 25mg bid artesunate, 50mg bid artesunate or placebo plus standard of care (prednisone plus mycophenolate mofetil ［MMF］) for 6 month.
All the subjects were asked to visit the hospital for weekly follow-up for four weeks, then monthly thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1, Subjects of either sex, 14-65 years of age, 2, Diagnosis of SLE according to the ACR criteria (1997), 3, Renal biopsy within 6 months prior to randomization with a histological diagnosis (ISN/RPS 2003 classification of LN) class III, IV, V, III+V and IV+V [excluding Class III(C), IV-S(C), and IV-G(C)], 4, Class IV or IV+V LN: proteinuria ≥1g/24hr (or Urinary protein: creatinine ratio≥ 1.0) or Scr>1.3mg/dl, with active urinary sediment [> 5 RBCs/hpf or> 5 WBCs/hpf (or within the reference range of the laboratory) in absence of menses and genitourinary tract infection, or presence of cellular casts (RBC or WBC casts)], 5, Class III, III+V or V LN: proteinuria ≥2g/24hr (or Urinary protein: creatinine ratio ≥ 2.0) or Scr>1.3mg/dl, 6, Provision of written informed consent by subject or guardian.
排除标准
- •eGFR<30ml/min/1.73m2,
- •Subjects who have previously failed both MMF (or other forms of mycophenolate) induction therapies,
- •Subjects who received an induction therapy with CTX or MMF within 3 months prior to the planned initiation of the current induction for the study,
- •Have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of baseline (Day 0),
- •Have acute or chronic infection requiring management based on the investigator's opinion,
- •Pregnant, nursing or under unreliable contraceptive method,
- •Subjects who have been on continuous dialysis starting >2 weeks before randomization into the induction phase and/or continuous dialysis with an anticipated duration >8 weeks,
- •Have a history of kidney transplant or a plan of kidney transplant,
- •Known hypersensitivity or contraindication to any drug products or any component of these drug products they plan to receive (e.g. Artesunate, CTX, MMF, AZA, corticosteroids),
- •Have severe acute or chronic diseases (e.g. cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at under risk,
- •Have a history of malignant neoplasm within the last 5 years, except for adequately treated carcinoma in situ of the uterine cervix,
- •Recruited by other trial and/or use study agent within 4 weeks.
研究组 & 干预措施
low dose Art
25mg bid Artesunate and standard of care was given to patients
干预措施: Artesunate (Drug)
high dose Art
50mg bid Artesunate and standard of care was given to patients
干预措施: Artesunate (Drug)
placebo
Placebo and standard of care was given to patients
干预措施: placebo (Other)
结局指标
主要结局
Remission
时间窗: 6 month
1. Complete remission: Proteinuria \< 0.3g/ 24hr, no active urinary sediment, normal albumin, stable Scr (within 15% fluctuation). 2. Partial remission: Proteinuria between 0.3 and 2.9g /24hr and a decrease in value of at least 50% of base value, albumin≥30g/L, stable Scr (within 15% fluctuation).
次要结局
未报告次要终点
研究者
Xue Qing Yu
Professor of Medicine Director, Institute of Nephrology The First Affiliated Hospital Sun Yat-Sen University
Sun Yat-sen University