Multi-centre, Double-blind, Randomised, Active- and Placebo-Controlled, Confirmatory Trial to Demonstrate Efficacy and Safety of Traumed® Gel in Patients Having Acute Ankle Sprain
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 809
- 试验地点
- 1
- 主要终点
- Area Under the Curve (AUC)* for pain on passive movement in Visual Analog Scale (VAS) from Baseline to Day 4.
研究概览
简要总结
TRAUMED - a randomized clinical trial evaluating the efficacy and safety of Traumed® gel in patients with acute ankle sprain.
详细描述
Lateral ankle sprains are the most prevalent musculoskeletal injuries in physically active populations. They also have a high prevalence in the general population and pose a substantial healthcare burden. The injury mechanism is characterized by a high velocity inversion and internal rotation of the ankle/foot complex. The treatment for acute lateral ankle sprain is quite variable, with many patients returning to activity in a short period of time; however, half of the affected population may never seek initial care. Inadequate treatment of ankle sprains can lead to chronic problems such as decreased range of motion, pain, and joint instability.
Controlled trials of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in patients with ankle sprain showed that compared with placebo, NSAIDs were associated with improved pain control and function, decreased swelling, and more rapid return to activity. Diclofenac is meanwhile considered to be the gold standard in the treatment of joint sprains and other conditions. Topical diclofenac is well tolerated and is associated with fewer side-effects than other topical NSAIDs, mostly mild, easily resolved local skin irritation.
The current trial is designed to demonstrate the superior efficacy of Traumed® gel versus placebo and to assess the non-inferiority of Traumed® gel compared to diclofenac gel. After evaluation of entry criteria patients will be randomized to investigational treatment, which will be Traumed® gel or diclofenac gel or matching placebo gel, administered locally on the area of the injury, 3 times daily for 7 days. After end of the 7-day treatment phase patients will be followed up for another 7 days. Consequently the entire duration of the trial for each patient will be 14 days.
Patients will receive paracetamol (acetaminophen) 500 mg/tablets as rescue medication to be taken for pain relief when necessary.
All patients will receive soft support (elastic bandage). Grade 2 patients will receive a semi-rigid removable brace on Day 7.
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)
盲法说明
CRO (including CRAs)
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
- •Acute unilateral Grade 1 or Grade 2 sprain of the lateral ankle.
- •>/=18 years of age.
- •Legally competent male or female outpatient.
- •Injury occurred within previous 24 hours before first treatment expected.
- •Signed Informed Consent.
- •After 5 minutes of rest, pain on passive movement by investigator measured by Visual Analog Scale (VAS) >50 mm.
- •Not pregnant or breast-feeding.
排除标准
- •Similar injury affecting the same joint within the past 6 months.
- •Bilateral ankle injury.
- •Grade 3 ankle sprain.
- •Fracture of the ankle (It should be excluded by using e.g., the Ottawa Ankle Rules. In case of any doubt the exclusion of fracture by x-ray should be considered as per standard of care).
- •Chronic joint disorders such as clinically relevant osteoarthritis or aseptic arthritis
- •Disorders that may lead to joint oedema for other reasons than ankle sprain (such as heart failure, thrombosis, lymphedema and others).
- •Diagnosis requiring bed rest, hospitalization, surgery, or use of any cast during the planned treatment period.
- •Debilitating acute or chronic illness.
- •Use of systemic and /or topical corticosteroids in the previous 8 weeks, any analgesics (e.g., paracetamol / acetaminophen) in the previous 24 hours before Screening Visit, or 48 hours in the case of long-acting NSAID, cyclooxygenase type 2 (COX-2) specific inhibitors, or tramadol and other opioids. Low dose acetylsalicylic acid (70 - 100 mg per day) for anti-thrombotic therapy is permitted if doses are stable for the month prior to Screening Visit and planned to be stable during the entire study.
- •History of sensitivity to any component of the study drugs (including e.g. paracetamol / acetaminophen intolerance; patients in whom asthma attacks, skin rash or acute rhinitis are triggered by acetylsalicylic acid or non-steroidal anti-inflammatory drugs (NSAIDs).
- •Unwilling or unable to comply with all the requirements of the study protocol.
- •Concurrent injury to proximal structures in ipsilateral lower extremity (i.e., concurrent shin, knee, thigh, or hip injury).
- •History of ligament avulsion, fracture or surgery to the affected lower extremity.
- •Presence of infections and/or skin diseases in the area of the study treatment site (including psoriasis).
- •Any previous treatments of the injured ankle, whether topical or systemic, are prohibited except RICE (simultaneous combination of all 4 elements; Rest, Ice, Compression and Elevation; which is restricted to be used until starting treatment with the investigational drug).
研究组 & 干预措施
Test product
Traumed® gel (human gel galenic form of Traumeel®)
干预措施: Traumeel® (Drug)
Reference product
Diclofenac sodium gel 1%
干预措施: Diclofenac sodium gel 1% (Drug)
Placebo therapy
Corresponding placebo gel
干预措施: Placebo (Drug)
结局指标
主要结局
Area Under the Curve (AUC)* for pain on passive movement in Visual Analog Scale (VAS) from Baseline to Day 4.
时间窗: Baseline and Day 4
Ankle pain is assessed via a 100 mm VAS, where zero mm indicates 'no pain' and 100 mm indicates the 'most severe imaginable pain' in relation to the participant's ankle sprain. After 5 minutes rest, participants first assess their ankle sprain pain on a 100 mm VAS for a secondary efficacy assessment. With the participant still at rest, the investigator performs 10° dorsal-flexion and 30° plantar-flexion of the sprained ankle, before participants re-assess their pain on a 100 mm VAS.
Area Under the Curve (AUC) for pain on passive movement in Visual Analog Scale (VAS) from Baseline to Day 7 as per SAP version 1.0.
时间窗: Baseline and Day 7
Ankle pain is assessed via a 100 mm VAS, where zero mm indicates 'no pain' and 100 mm indicates the 'most severe imaginable pain' in relation to the participant's ankle sprain. After 5 minutes rest, participants first assess their ankle sprain pain on a 100 mm VAS for a secondary efficacy assessment. With the participant still at rest, the investigator performs 10° dorsal-flexion and 30° plantar-flexion of the sprained ankle, before participants re-assess their pain on a 100 mm VAS.
次要结局
- AUC for pain at rest in VAS from Baseline to Day 4.(Baseline and Day 4)
- AUC for pain on passive movement in VAS from Baseline to Day 2, 7 and Final Visit.(Baseline, Day 2, Day 7 and Day 14)
- AUC for pain at rest in VAS from Baseline to Day 2, 7 and Final Visit.(Baseline, Day 2, Day 7 and Day 14)
- Change from Baseline of pain on passive movement in VAS to Day 4, 7 and Final Visit.(Baseline, Day 4, Day 7 and Day 14)
- Change from Baseline of pain at rest in VAS to Day 4, 7 and Final Visit.(Baseline, Day 4, Day 7 and Day 14)
- Change from Baseline to Day 2, 4, 7 and Final Visit in the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) sub-scale.(Baseline, Day 2, Day 4, Day 7 and Day 14)
- Amount of rescue medication (doses) required for pain relief.(Baseline, Day 4, Day 7 and Day 14)
- Time to 50% improvement of pain at rest measured by VAS at participant visits.(Baseline through to Day 14)
- To assess the tolerability and safety of Traumed® gel as measured by the number of participants experiencing Adverse Events.(From signature of Informed consent (Day 1) to Final Visit (Day 14))