Tong-Luo-Qu-Tong Plaster for KOA: a Randomised, Double-blind, Parallel Positive Control, Multi-center Clinical Trial

Study on Efficacy, Safety and Economy of Tong-Luo-Qu-Tong Plaster Treatment for Knee Osteoarthritis: Study Protocol for a Randomised, Double-blind, Parallel Positive Control, Multi-center Clinical Trial

Knee osteoarthritis(OA), also known as degenerative arthritis, have affected a lot of people. Patients with severe osteoarthritis frequently develop one or more of the typically following symptoms: joint pain, stiffness, activity with joint friction noise, limited mobility, such as difficulty walking and climbing. Now there are many western medicine treatments including symptom relief and joint cartilage protective agents for OA, but the results have not yet satisfied. TCM treatment of osteoarthritis has remarkable curative effect and unique advantage.Tong-Luo-Qu-Tong Plaster is a common method to treat osteoarthritis of the knee for thousands of years in China. It lacked a large sample randomised, double-blind, parallel positive controlled, multicenter clinical trial, and the clinical evidence of Tong-Luo-Qu-Tong Plaster for Knee Osteoarthritis need to be further completed.

A randomised, double-blind, parallel positive controlled, multicenter clinical trial will be conducted to assess the effectiveness and safety of Tong-Luo-Qu-Tong Plaster on patients with knee osteoarthritis. A total of 2000 patients with knee osteoarthritis will be recruited and randomly allocated into experimental group(1500) or control group(500). Each patient will undergo a 2-week treatment with herbal patches for one session per day.The western Ontario and McMaster universities osteoarthritis index (WOMAC) as objective indicators of efficacy is the primary efficacy endpoint of the study.The secondary outcome measures are the changes in TCM syndrome quantitative score, Visual Analog Scale/Score (VAS) score of pain, and the effective time of pain relief of drug from the baseline to 1 week, 2 weeks' follow-up.

Inclusion Criteria:

• Participants who have symptomatic knee osteoarthritis, diagnosis of KOA was based on criteria developed by the American College of Rheumatology(ACR) in 1986
• The differentiation standard of the arthralgia syndrome of traditional Chinese medicine(TCM): Referring to the Guidelines on the clinical research of Chinese medicine new drugs(2002)
• The visual analog scale score is no less than 30 mm.
• The patient is older than or equal to 40 years old
• All the patients signed informed consent form before study begins

Exclusion Criteria:

• Hormone therapy was used in the first month of screening
• Arthroscopy and intra-articular injection was performed on the knee joint which is going to be evalued during the first three months of screening.
• There is a history of trauma or surgery in the knee joint six months before screening or participants who a history of lessmore than three trauma or surgical procedures in the knees
• Participants who have knee arthroplasty, lumbar spinal stenosis, ankylosing spondylitis, rheumatic arthritis, rheumatoid factor positive(>40), eallergic constitution and mental disorder will be excluded from the trial
• Patients has severe diseases and complications such as severe diabetes, serious liver and kidney disease, malignant tumors, infectious diseases or complications affecting the knee joints
• Pregnant,lactating women
• Subjects are participating in or have participated in other clinical trials in the first three months.
• Subjects cannot stop using the drugs immediately with a long-term use of other related drugs.
• Combined with severe primary diseases such as hepatic renal functionand hematopoietic system, such as liver function (ALT≧1.5×ULN), and kidney function(AST≧1.5×ULN)