Evaluation of The Efficacy And Safety of Intra-Articular Etanercept in Patients With Refractory Knee Joint Synovitis: a Placebo Controlled, Single-Blind, Crossover-Trial, With Randomisation of Treatment Sequence
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Thompson articular index
研究概览
简要总结
To assess the therapeutic efficacy, of the clinical response of intraarticular (IA) etanercept (E) 12.5 mg or placebo (P: NaCl) injections into single knee arthritic joint of patients with refractory knee joint synovitis (KJS), administered once every two week, for eight weeks, with cross over after 2 weeks, in two groups of randomly assigned patients, for whom traditional systemic disease-modifying antirheumatic drugs (DMARDs) is insufficient or inappropriate. The primary outcome measure is the Thompson articular index of KJS disease activity.
详细描述
The study is a single centre, placebo-controlled, single-blind, cross-over trial, with randomization of treatment sequence and open-label extension to be conducted in rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies patients with resistant knee joint synovitis (KJS).
Patients are eligible if they suffered from persistent active KJS (characterized by pain, tenderness, and effusion), which had proved resistant to surgical treatment or to repeated IA corticosteroid therapy, or unresponsive to a minimum of 6 months second-line drug therapy with DMARD-, and/or anti-TNFα biologic agent monotherapy and systemic oral corticosteroid treatment, or to a combination therapy (drug failure is defined as discontinuation because of intolerable adverse effects or lack of clinical efficacy).
Concomitant Treatments: stable, appropriate doses of DMARDs (methotrexate, sulfasalazine, hydroxychloroquine, cyclosporine), DMARD combinations or low dose oral corticosteroids (≤10 mg prednisone) with or without non-steroid anti-inflammatory agents will be continued throughout the study.
Patients will be permitted stable doses (no greater than the maximum dose recommended by the manufacturer) of non-steroidal anti-inflammatory drugs (NSAIDs) but will be permitted to use only one NSAID at any given time. No analgesic could be taken before undergoing assessment on the day clinical evaluations will be performed.
Treatment: Each dose of study drug will be administered as one intraarticular (IA)injection carried out in each single knee joint that will be randomly assigned to blind treatment with 0.5 ml of etanercept (E) (12.5mg) or placebo (P) (NaCl). The IA injection will be administered once every two weeks for an eight week period. After 2 weeks time the patients will be crossed-over and each arthritic knee joint will receive E (12.5 mg) for four times or P for three times, respectively, administered every two weeks for an eight week period. All the IA injections will be administered after synovial fluid aspiration by the same operator. The study, patients with KJS flare up after IA injection will be asked to enter the open-label IA extension treatment with IA-E injection once every two weeks, for eight weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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
- •Male or female patients 18 years of age or older and of legal age of consent.
- •A negative serum pregnancy test at screening and use of a medically acceptable form of contraception starting at screening and continuing throughout the study, is required for all females of childbearing potential (defined as an oral, injectable, or implantable contraceptive, intrauterine device, or barrier method combined with a spermicide).
- •Meet the 1987 American Rheumatism Association (ARA) revised criteria for Rheumatoid Arthritis(RA) and generally accepted criteria for psoriatic (PsA) or spondyloarthritides (SpA).
- •Meet the following criteria at both the screening visit and the baseline visit:
- •Refractory KJS defined by the presence of: Persistence of active synovitis of the knee (characterized by pain, tenderness and effusion), which had proved resistant to at least 6 months second-line DMARD therapy
- •Failure drug therapy with at least one DMARD and/or anti-TNFα biologic agent, and/or systemic or IA corticosteroid treatment. (Drug failure is defined as a drug discontinuation because of lack of clinical efficacy or intolerable adverse effects).
- •Normal chest X-ray as clinically indicated.
- •Provide written informed consent.
- •In the opinion of the investigator, the patient will be able to comply with the requirements of the protocol.
排除标准
- •Uncooperative patients with a history of poor compliance.
- •Known hypersensitivity to etanercept or any of its components.
- •Known significant concurrent medical disease including:
- •cancer or history of cancer (other than resected basal cell carcinoma of the skin)
- •congestive heart failure
- •myocardial infarction within 12 months of the screening visit
- •uncontrolled angina pectoris
- •active infection
- •sepsis or at risk of sepsis
- •severe pulmonary disease
- •known HIV infection
- •liver function abnormality (SGOT/AST, SGPT/ALT: greater than two times the upper limit of normal); liver cirrhosis or fibrosis
- •renal disease (creatinine level >175umol/L)
- •leukopenia (white blood cells <3.5 x 109/L)
- •thrombocytopenia (<1.25 x 1011/L)
- •haemoglobin </= 8.5 g/dL
- •Females who are pregnant, breast feeding or at risk of pregnancy and not using a medically acceptable form of contraception.
- •Any condition judged by the investigator that would cause the study to be detrimental to the patient.
- •Use of any investigational drug within four weeks of the screening visit.
- •In the opinion of the investigator, the patient shows persistent signs of immunosuppression.
- •Receipt of any live attenuated vaccine within eight weeks before the screening visit.
结局指标
主要结局
Thompson articular index
时间窗: 2 weeks
次要结局
- Knee Joint Articular Index(2 weeks)