Multi-center Double-blind Randomized Controlled Trial to Evaluate Effectiveness and Safety of Co-administered Traumeel® / Zeel® Intra-articular Injections vs Placebo in Patients With Moderate-to-Severe Pain With Osteoarthritis of the Knee
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 287
- 试验地点
- 28
- 主要终点
- Change in Knee Pain as Measured by the WOMAC Osteoarthritis (OA) Index Pain Subscale (Section A, Items #1-5) Measured by 100 mm VAS
研究概览
简要总结
The aim of this study is to evaluate the effectiveness and safety of a combined Traumeel® / Zeel® injection against placebo (saline) in patients with moderate-to-severe pain associated with osteoarthritis of the knee.
详细描述
The primary objective is to demonstrate the superiority of Traumeel® and Zeel® co-administered intra-articular (IA) injections vs placebo IA injections on the change in knee pain in patients with moderate to severe knee pain associated with osteoarthritis.
The secondary objectives are to evaluate reduction of pain and stiffness and change in physical function.
Safety is evaluated by the incidence of treatment emergent adverse events during the treatment period and follow up period for all randomized patients.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Known hypersensitivity or allergy to any of the components of Traumeel or Zeel
- •Known hypersensitivity or allergy to acetaminophen.
- •Has body mass index (BMI) >38 kg/m
- •Avoidance of, or aversion to, nonprescription medications.
- •Clinical symptoms of meniscal instability or significant valgus/ varus that requires corrective osteotomy
- •Any major injury or surgery to the target knee in the prior 12 months.
- •One or a combination of the following co-morbidities:
- •other inflammatory arthropathies, gout or pseudogout within previous 6 months
- •avascular necrosis
- •severe bone or joint deformity in target knee
- •osteonecrosis of either knee
- •fibromyalgia
- •pes anserine bursitis
- •lumbar radiculopathy with referred pain to either knee
- •neurogenic or vascular claudication
- •significant anterior knee pain due to diagnosed isolated patella-femoral syndrome in the target knee
- •target knee joint infection or skin disorder/infection to the area surrounding the knee within previous 6 months
- •current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin)
- •Participated in any experimental drug or device study within the prior one (1) month and/or IA injections six (6) months.
- •Referred pain from other joints
- •Significantly debilitating concurrent infection(s)
- •Significant ligamentous instability
- •Any prior viscosupplementation therapy (in target knee) within 6 months prior to Screening
- •Systemic or IA injection of corticosteroids in any joint within 3 months of enrollment
- •Therapy with oral hyaluronic acid products, and/or oral pharmaceutical products containing glucosamine and/or chondroitin sulphate and/or diacerein
- •Therapy with opioids within the last 90 days including intra-dermal delivery systems (patches)
- •Therapy with autologous stem cells
- •Therapy with coumarins such as warfarin, Coumadin; heparin and derivative substances including low molecular weight heparin, synthetic pentasaccharide inhibitors of factor Xa such as fondaparinux and idraparinux; direct factor Xa inhibitors such as rivaroxaban and apixaban; direct thrombin inhibitors such as hirudin, lepirudin, bivalirudin, argatroban and dabigatran.
- •Concomitant inflammatory or other rheumatologic, neurological or cardiovascular diseases which could affect the evaluation of knee pain
- •Ongoing litigation for workers compensation for musculoskeletal injuries or disorders
- •Use of alcohol of more than 4 drinks per day
- •Clinically important axial deviation (varus, valgus) greater than 15 degrees
- •Concomitant severe OA of the hip or other joints, which might interfere with the assessments required by the study
- •Painful knee conditions other than OA (e.g., Paget's disease)
- •Hemiparesis of lower limbs
- •Significant planned surgery to lower limbs, which might interfere with the patient's ability to comply with study requirements
- •Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular, neurological disease that might interfere with the outcome of the study or the patient's ability to comply with study requirements
- •Presence of infections and/or skin diseases in the area of the injection site such as psoriasis
- •Females who are pregnant or breast-feeding or not using recognized effective contraceptive measures. Females of childbearing potential (including those less than one year post-menopausal) must agree to maintain reliable birth control throughout the study.
- •Clinically significant abnormal laboratory values.
- •Patients who are likely to be non-compliant or uncooperative during the study.
研究组 & 干预措施
Traumeel® / Zeel® Injectable Solution
Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one intra articular (IA) injection) on treatment days 1, 8 and 15.
干预措施: Traumeel® / Zeel® Injectable Solution (Drug)
Placebo injectable solution
Injection volume of placebo is 4.2 mL as well (taken from the 10.0 mL vial by unblinded staff member, rest to be kept for drug accountability)
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Knee Pain as Measured by the WOMAC Osteoarthritis (OA) Index Pain Subscale (Section A, Items #1-5) Measured by 100 mm VAS
时间窗: from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)
Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess pain, scores from WOMAC Section A, items 1 to 5 are averaged to yield the Pain Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. A two-sided test of equality of the study drug (Traumeel®-Zeel®) and Placebo at level 0.05 was computed using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and the corresponding Baseline value of the primary efficacy variable as a covariate. The test decision was based on the (two-sided) p-value for the corresponding test of no treatment difference.
次要结局
- Pain Subscore (WOMAC Section A, Items #1-5) Measured by 100 mm VAS(from Baseline to post-Baseline visits except End of Study Visit (up to day 105))
- Stiffness Subscore (WOMAC Section B, Items #6-7) Measured by 100 mm VAS(from Baseline (Day 1, predose) to End of Study Visit (up to Day 119))
- Physician Global Assessment (PhGA)(End of Study Visit (up to Day 119))
- Pain Immediately Following the 50-foot Walk (100 mm VAS)(Baseline (Day 1, predose) to post-Baseline visits (up to day 119))
- Total WOMAC Score (All Subscales) Recorded on 100 mm VAS(from Baseline (Day 1, predose) to End of Study Visit (up to Day 119))
- Time to Walking (50-foot Walk Test)(Baseline (Day 1, predose) to post-Baseline visits (up to day 119))
- Patients Achieving 100% Pain Relief(Statistically derived)
- Physical Function Bubscore (WOMAC Section C, Items #8-24) Recorded on 100 mm VAS(from Baseline (Day 1, predose) to End of Study Visit (up to Day 119))
- Patient Global Assessment (PGA)(End of Study Visit (up to Day 119))
- Time to 50% Pain Relief (Study Population Measure Statistically Derived)(Statistically derived)
- Time to and Use of Rescue Medication (Acetaminophen up to 3000 mg Per Day for Breakthrough Pain) (Study Population Measure Statistically Derived) - Patients Use(Statistically derived)
- Time to and Use of Rescue Medication (Acetaminophen up to 3000 mg Per Day for Breakthrough Pain) (Study Population Measure Statistically Derived). Tablets Taken.(Statistically derived)