A Randomized Placebo Controlled Trial to Assess the Structural Effect and Long-term Symptomatic Relief of Repeated Intra-articular Injections of Hyaluronic Acid in Primary Knee Osteoarthritis
试验速览
- 阶段
- 不适用
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- Joint Space Width
研究概览
简要总结
The present study is designed to test the hypothesis that Intra-Articular Hyaluronic Acid (IAHA) is superior to placebo in slowing structural progression and on long term symptomatic effect in primary knee Osteoarthritis (OA) patients.
The investigators will perform a multicenter double-blind, randomized, placebo-controlled, parallel group trial.
详细描述
The target population will be patients with the diagnosis of knee osteoarthritis who are followed at two Portuguese hospitals (Centro Hospitalar de Lisboa Norte - Hospital Santa Maria, Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz).
All patients selected will be included in the intention-to-treat group. Then, using blocked randomization method they will be assigned to receive either IAHA, or placebo (saline solution). At both hospitals the study will consist of four injections of IAHA, 6 months apart, plus a 6 month period after the injection, resulting in a total follow-up period of 24 months. Before each new cycle a follow-up consultation will be performed in order to assess pain and function (KOOS), quality of life (SF-36), adverse events and consumption of acetaminophen and NSAIDS regarding the week before evaluation. X-rays will be performed in the beginning of follow-up, one year after that and 6 months after the last cycle of IAHA or placebo injections (24 months).
Ultrasound evaluation will be performed at the target knee in same time points as X-rays by two rheumatologists trained in musculoskeletal ultrasound examination. Additionally, the investigators will assess potential biochemical biomarkers of knee OA structural progression and response to treatment. Measurements will be performed in both serum and urine and, If possible, synovial fluid aspiration will be performed and together with blood and urine samples stored at the Biobanco-IMM Instituto de Medicina Molecular for analysis. Biologic samples collection will be performed at baseline and repeated at the 4th, 12th, 24th, 36th weeks, and then every 6 months.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic knee OA as defined by the ACR clinical and radiographic criteria
- •Kellgren-Lawrence grade of II or III on prior x-rays (taken within 6 months of the screen visit) or screen X-ray
- •A minimum medial and/or lateral JSW of the target knee of 2 mm
- •Knee pain of 40 mm or greater on a 100 mm visual analogue scale (VAS) at any time during the week before inclusion
- •Oral corticosteroids (≤10 mg/day prednisolone or equivalent), NSAIDs, and acetaminophen are permitted if the dose had been stable for at least one month prior to baseline
排除标准
- •Body mass index greater than 40 kg/m2
- •Varus or valgus deformity of the knee > 15 degrees (assessed by goniometry)
- •History of trauma, surgery or planned surgery to the study joint (including arthroscopy surgery), joint inflammatory diseases, septic arthritis and/or microcrystalline arthropathies
- •Coagulation/platelet disorders
- •Active malignancy, active systemic infection, or any contraindication to MRI
- •Potent analgesics including opiates, oral corticosteroid therapy within one month prior to enrolment into the study other than stable doses of ≤ 10 mg daily prednisolone or equivalent
- •Knee administration of intra-articular steroids in the previous 3 months or HA injections during the past year
结局指标
主要结局
Joint Space Width
时间窗: 2 years
Mean change of minimal JSW of the most affected compartment of the tibiofemural joint in both placebo and IAHA groups at the end of follow-up (2 years).
次要结局
- OMERACT/OARSI 2004 response(2 years)
- Ocurrence of Knee replacement surgery(2 years)
- Acetaminophen Consumption(2 years)
- NSAIDs(2 years)
- SF-36 questionnaire - Physical Score(2 years)
- SF-36 questionnaire - Mental Score(2 years)
- Euro QoL 5D(2 years)
- Adverse events(2 years)
- Visual Analog Scale(2 years)