A Randomized, Double Blind, Placebo Controlled Pilot Trial of Rituximab for Non-splenectomized Adults With Acute Immune Thrombocytopenic Purpura Receiving Standard Treatment (R-ITP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 7
- 主要终点
- rescue therapy
研究概览
简要总结
The purpose of this study is to assess the feasibility of a randomized, double blind, placebo controlled trial of add-on rituximab for non-splenectomized adults with acute immune thrombocytopenic purpura (ITP).
详细描述
Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by severe thrombocytopenia and bleeding. With current standard therapies, adult-onset ITP tends to recur thus exposing patients to prolonged risks of hemorrhage and toxicities of standard treatments. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effectively raise the platelet count in some patients with ITP and there is clinical and biological evidence to suggest that, if given early, rituximab may prevent ITP relapses.
We have designed a randomized, double blind, placebo controlled pilot trial of rituximab for the treatment of non-splenectomized adults with acute ITP who are receiving standard treatments. The primary objectives of this trial are to determine the feasibility of recruitment, randomization and blinding; the safety of rituximab in ITP; and the event rate in the control group which will be used to calculate the sample size for a larger trial. Secondary objectives are to determine rates of 6-month event free survival where an event is defined as any of: a platelet count <50; the need for rescue treatment; or significant bleeding. Data from this pilot trial will inform the design of a larger phase III trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-splenectomized patients with acute ITP, where "acute ITP" is defined as a platelet count below 30 at the time that standard treatment was recommended by a physician and for which no treatment had been received for the preceding 30 days.
- •Must be receiving standard ITP treatment.
排除标准
- •Cardiac arrhythmia.
- •Uncontrolled hypertension or inability to hold antihypertensive medications for 12 hours prior to and throughout study drug infusions.
- •Known coronary artery disease, angina pectoris or myocardial infarction within the last year.
- •Significant pulmonary disease within the last year.
- •Stroke, transient ischemic attack or venous thrombosis within the last year.
- •Secondary causes of thrombocytopenia (splenomegaly [palpable spleen or radiologically confirmed >14 cm], drug-induced thrombocytopenia, hereditary thrombocytopenia, microangiopathic hemolytic anemia, myelodysplastic syndrome).
- •Chronic lymphocytic leukemia or lymphoma.
- •Active or metastatic cancer.
- •History of hepatitis B or C or HIV.
- •Active infection in the 4 weeks before randomization.
- •Inherited coagulation factor deficiency.
- •Aspirin, aspirin-containing compounds, salicylates, non-steroidal anti-inflammatory medications (NSAIDS) medications, clopidogrel or ticlopidine in the 7 days preceding study drug infusions; vitamin K antagonists (warfarin) in the 3 days preceding study drug infusions; unfractionated heparin or low molecular weight heparin in the 24 hours preceding study drug infusions.
- •Elevated INR or prolonged PTT; LDH, serum creatinine, liver function tests (AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin) increased more than 1.5 times upper limit of normal.
- •Prior rituximab treatment.
- •Unable to schedule 4 weekly study infusions.
- •Pregnancy or breastfeeding.
- •Known sensitivity to murine proteins, Chinese Hamster Ovary (CHO) cell proteins or to any component of rituximab.
- •Participation in another clinical trial.
- •Geographic inaccessibility.
- •Failure to provide written informed consent.
- •Any additional laboratory test result, health related illness or other diagnosis which, in the opinion of the treating physician, may put the subject's health or safety at risk.
研究组 & 干预措施
A
Rituximab
干预措施: Rituximab (Drug)
B
Saline placebo iv infusion
干预措施: Placebo (Drug)
结局指标
主要结局
rescue therapy
时间窗: 6 months
Event free survival in controls
时间窗: 6 months
Bleeding
时间窗: 6 months
Feasibility of recruitment
时间窗: 3 years
Degree of adherence to the study protocol
时间窗: 3 years
次要结局
- Platelet count response(6 months)
- Quality of life(6 months)
- Circulating CD-20 positive lymphocytes(6 months)
- Platelet associated IgG(6 months)
研究者
Donald Arnold
MD
McMaster University