Multicenter Double-blind Randomized Comparative Placebo-controlled Study of Efficacy and Safety of Intra-articular HBISA Endoprosthesis of Synovial Fluid (NOLTREX™) in Knee Osteoarthritis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 144
- 试验地点
- 4
- 主要终点
- Change of the Total WOMAC Score (WOMAC-T)
研究概览
简要总结
The aim of this double-blinded controlled study is to assess clinical efficacy and safety of intra-articular HBISA Endoprosthesis of Synovial Fluid (polyacrylamide hydrogel) in comparison with placebo (0.9% sodium chloride solution) in Kellgren Lawrence radiological grade II-III knee osteoarthritis
详细描述
Polyacrylamide hydrogel (hereinafter - PAAG) is intended for a symptomatic effect leading to decrease of joint pain intensity and improvement of functional joint characteristics. Therefore PAAG is regarded as symptom-modifying therapy for joint osteoarthritis (hereinafter - OA). The aim of this study was to estimate efficacy and safety of intra-articular injections of PAAG in comparison with saline solution. Men and women above 50 years with verified knee osteoarthritis in accordance with the American College of Rheumatology (ACR) criteria were randomly assigned to one of 2 groups (PAAG or saline solution). Each patient received to the target knee joint one injection of 4.0 ml either PAAG or placebo with one-week interval. Course - 2 injections. To avoid the joint overfilling with the dense, slowly resorbing material in patients with a good clinical result, the course of injections was to be stopped. Primary and secondary efficacy endpoints, and safety parameters were assessed at weeks 6, 13 and 25 visits .
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
A patient, study investigator and Sponsor representative (monitoring specialist) will not know to which group a patient is included. to preserve blinding of any patient and study team, an independent unblended physician is to be engaged, he/she will receive the product per randomization code and perform the procedure of intra-articular injection of the study MD and placebo.
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
- •Men and women above 50 years;
- •Verified knee osteoarthritis in accordance with the ACR (knee pain combined with one of the following signs: age above 50 years, knee crepitus or morning joint stiffness lasting for less than 30 minutes combined with radiologic signs of knee osteoarthritis);
- •Kellgren Lawrence radiological grade II-III knee osteoarthritis with the predominant involvement of the medial tibiofemoral region of the knee joint;
- •Joint space width (JSW) of the target knee joint at least 2.5 mm.
排除标准
- •History of any injury or surgical intervention on the target knee joint (except for diagnostic arthroscopy made not longer than 60 days at the study entry);
- •Severe degenerative changes in the target knee joint determined as the joint space narrowing less than 2 mm;
- •Varus or valgus deformation of the target knee joint;
- •Instability of the target knee joint;
- •Active inflammation of the target knee joint (edema, hyperemia, present effusion) at the study entry;
- •Microcrystalline arthropathies;
- •Systemic inflammatory disease (rheumatoid arthritis, systemic lupus erythematosus, etc.);
- •Seronegative spondyloarthritis and reactive arthritis;
- •Inflammatory diseases of the skin and soft tissues in the proposed injection site for the test MD or placebo in the target joint;
- •History of venous thrombosis and thromboembolia;
- •Coagulogram abnormalities (APTT, prothrombin time, prothrombin index, fibrinogen);
- •Inflammatory changes in the complete blood count (leukocytosis, increase of erythrocyte sedimentation rate [ESR]);
- •Platelet count abnormality (in accordance with the reference ranges of the local laboratory;
- •Increase of rheumatoid factor level;
- •Increase of uric acid level > 360 μmol/l;
- •Diabetes mellitus;
- •Hemophilia and other hemorrhagic diatheses, as well administration of anticoagulants and disaggregants;
- •Positive results of HIV, HBs-Ag, anti-HCV, RW tests;
- •Intra-articular injection to the target knee joint:
- •Noltrex - within 24 months prior patient's inclusion to the study;
- •hyaluronates - within 6 months prior patient's inclusion to the study;
- •glucocorticosteroids - within 1 month prior the study inclusion;
- •non-steroidal anti-inflammatory drugs (NSAID) - within 3 weeks prior patient's inclusion to the study.
- •Oral administration of non-steroidal anti-inflammatory drugs (NSAID) within 2 weeks prior the study inclusion;
- •Necessity of systemic glucocorticosteroids in any dosage form;
- •Paracetamol administration within 48 hours prior the study inclusion;
- •Pregnancy and lactation;
- •Hypersensitivity to components of the test MD or placebo;
- •Severe liver disorder determined as the increase of one of the values: ALT, AST, ALP, total bilirubin, GGTP more than 3 times the upper limit of normal;
- •Renal diseases with the glomerular filtration rate estimated per Cockraft-Gault formula less than 60 ml/min/1.73 m2 (III-V stage chronic renal disease [CRD]);
- •Clinically manifest hip osteoarthritis;
- •History of knee and coxofemoral endoprosthesis;
- •Acute infectious diseases or infectious aggravations of chronic diseases (respiratory infections) within one month prior the study inclusion;
- •Severe decompensated chronic or acute diseases and other conditions which, by the opinion of the study physician, may preclude the patient's participation in the study or affect the study results.
结局指标
主要结局
Change of the Total WOMAC Score (WOMAC-T)
时间窗: baseline (week 1), week 25
Mean change from baseline (week 1) to visit 5 (Week 25) in the total WOMAC score. Patients were asked to complete the questionnaire during the study visit 5. The Western Ontario and McMaster Universities Osteoarthritis Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS and consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The scores for each subscale are summed up, with a possible score range of 0-500 for Pain, 0-200 for Stiffness, and 0-1700 for Physical Function. Higher scores represent worse pain, stiffness, and functional limitations. A sum of the scores for all three subscales gives a total WOMAC score (0-2400), where 0 represents the best health status and 2400 the worst possible status. The higher the score, the poorer the function.
次要结局
- The Pain Subscale Score WOMAC-A Changes(baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5))
- The Stiffness (WOMAC-B) and Functionality (WOMAC-C) Subscale Scores Changes(baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5))
- Patient Assessment of Treatment Efficacy(Week 6, Week 13 and Week 25)
- Investigator Assessment of Treatment Efficacy(Week 6, Week 13 and Week 25)
- Assessment of the Total Number of NSAID Tablets Taken(week 6 (visit 3), week 13 (visit 4), week 25 (visit 5))
- Assessment of the Total Number of Paracetamol Tablets Taken(week 6 (visit 3), week 13 (visit 4), week 25 (visit 5))
- Patient Exclusion Rates Due to Safety(Week 25)
- Exclusion Rate Due to Poor Patient Compliance(Week 25)
- Change of the Total WOMAC Score (WOMAC-T)(baseline (week 1), week 13 (visit 4))