Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients With Newly-Diagnosed or Relapsing IgA Vasculitis: A Prospective, Randomized, Controlled, Double-blind Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Hopital Foch
- 入组人数
- 75
- 试验地点
- 27
- 主要终点
- Rituximab efficacy
研究概览
简要总结
Systemic vasculitis are inflammatory diseases of the blood vessels, responsible for systemic manifestations. Among the systemic vasculitis affecting small blood vessels, IgA vasculitis (IgAV) is one of the most common forms and mainly affects the skin, joints, kidneys and gastrointestinal tract. Kidney and gastrointestinal damage can be serious, causing complications and life-threatening sequelae, especially in adults. The treatment of adult-onset IgAV is still a matter of debate. Glucocorticoids have been the standard of care for inducing remission for years in severe forms of IgAV. However, not all patients achieve remission and may experience disease flares associated with increased morbidity and mortality. In addition, the cumulative side effects of glucocorticoids are also major causes of long-term adverse events and death.Rituximab (RTX), an anti-CD20 monoclonal antibody, has been shown to be spectacularly effective in inducing remission in d 'other small vascular vessels, in particular ANCA-associated vasculitis and cryoglobulinemic vasculitis, with an acceptable safety profile.
Recently, a multicenter observational study suggested that RTX was an effective and safe therapeutic option for treating relapsed and / or refractory adult IgAV.
Overall, RTX may be an effective and safe therapeutic approach in adult IgAVs, justifying the need for a prospective randomized controlled trial evaluating Rituximab as an induction of remission for adult IgAV.
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
- Double (Participant, Investigator)
盲法说明
This trial will be comparative, randomized, double-blind and double-dummy in order to limit performance and evaluation bias.
Neither patients, nor physicians will know the treatments allocated to their patients.
Investigators will be in blind of the leukocyte formula during all study period, from day 1.
Neither patients, nor physicians will know the treatments allocated to their patients.
Investigators will be in blind of the CD19+ count during all study period, from day 15.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven diagnosis of IgAV according to Chapel Hill Consensus Conference definitions
- •Patient aged of 18 years or older
- •Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined by active manifestations attributable to IgAV
- •Patients with severe involvement of at least one organ
- •Patients within the first 21 days following initiation/increase of glucocorticoids at a dose < 1 mg/kg/day
- •Has signed an informed consent form prior to any study related procedures
- •Affiliated to a national health insurance
排除标准
- •Patients with ANCA-associated vasculitis, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
- •Patients with IgAV in remission of the disease,
- •Patients with severe cardiac failure defined as class IV in New York Heart Association,
- •Patients with severe, uncontrolled cardiac disease,
- •Patients with acute infections or chronic active infections (including HIV, HBV or HCV),
- •Patients with active cancer or recent malignancy (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,
- •Pregnant women and breastfeeding. Patients with childbearing potential must use reliable contraceptive methods throughout the study and at least for 12 months after the last study drug administration,
- •Patients with IgAV who have already been treated with rituximab within the previous 12 months,
- •Patients treated with immunosuppressive therapy within the last 3 months,
- •Patients with hypersensitivity to human or chimeric monoclonal antibodies,
- •Patients with contraindication to use rituximab,
- •Patients treated with any concomitant drugs contraindicated for use with the rituximab according to its SmPC,
- •Patients with contraindication to use routine care treatments (Glucocorticoids, Angiotensin-converting-enzyme (ACEis) or angiotensin receptor blockers (ARBs), dexchlorphéniramine),
- •Patients in a severely immunocompromised state,
- •Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric disorders, that could interfere with his/her compliance to protocol requirements,
- •Patients currently participating in another clinical study or 3 months prior to randomization,
- •Patients suspected not to be observant to the proposed treatments,
- •Patients unable to give written informed consent prior to participation in the study
- •Being deprived of liberty or under guardianship.
研究组 & 干预措施
control group
Control therapeutic strategy based on glucocorticoids plus placebo
干预措施: placebo (Drug)
experimental group
Experimental therapeutic strategy based on the use of rituximab in combination with glucocorticoids
干预措施: Rituximab Injection (Drug)
结局指标
主要结局
Rituximab efficacy
时间窗: 360 days
The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 360 days
次要结局
- Efficacy of rituximab-based regimen to induce remission(360 days)
- Assessement the duration of remission(360 days)
- Assessment of patients achieving a complete or partial renal remission & renal outcome remission(360 days)
- Measure of glucocorticoids dose(360 days)
- Number of participants with adverse events for the safety analyse(360 days)
- The sequelae assessed by the Vasculitis Damage Index(360 days)
- Quality of life of patients(360 days)
- Patient reported outcome(360 days)
- Patient survival(360 days)