Efficacy and Safety of Traditional Chinese Medicine (TCM) Comprehensive Therapy in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This is prospective randomized, controlled study to evaluate the efficacy and safety of Qingre Huoxue comprehensive therapy in treating of patients with early Rheumatoid Arthritis (RA). The major outcome index is the change from baseline to week 24 in Disease Activity Score (DAS28), and minor outcome indexes include American College of Rheumatology (ACR)20/50/70, PRO score, Sharp score and OMERACT RAMRIS score. The adverse events at any time were recorded to evaluate the safety.

Detailed Description
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Three arms were included in this study, and treatment with MTX and HCQ is defined as active comparator. Treatment of TCM，including Qingre Huoxue granule, Qingre Huoxue external preparation, MTX placebo and HCQ placebo, is defined as one experimental arm. Treatment of integrative medicine，including Qingre Huoxue granule, Qingre Huoxue external preparation, MTX and HCQ, is defined as another experimental arm.

Official Title
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Efficacy and Safety of Qingre Huoxue Comprehensive Therapy in the Treatment of Rheumatoid Arthritis (RA): A Randomized, Double-blind, Double-dummy, Multi-center Trial

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Treatment of MTX and HCQ
* Drug: Treatment of TCM
* Drug: Integrative Medicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with rheumatoid arthritis as determined by the 1987 ACR classification criteria. Diagnosed with TCM dampness heat and blood stasis syndrome The course of RA is not more than 5 years. Swollen joint (SJC)≥2 and tender joint count(TJC)≥3. Erythrocyte Sedimentation Rate（ESR）≥20 mm/hr Patients who take disease-modifying antirheumatic drugs for at least 3 months on a stable dose, and retain the same treatment during the study. Age 18-65 years with informed consent Exclusion Criteria: Patients with skin burst or allergies. Patients with cancer or other malignant disease such as cardiovascular, hematopoietic, liver and kidney disease, and psychopath Active or chronic infection, including HIV, hepatitis C virus, hepatitis B virus, tuberculosis Previous treated with tripterygii, glucocorticoid or biologic disease-modifying antirheumatic drug (DMARD) in 3 months. Previous treated with MTX or HCQ Patients with retinopathy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment of MTX and HCQ<br>Patients were treated with methotrexate (MTX), hydroxychloroquine (HCQ), oral Qingre Huoxue granule placebo and Qingre Huoxue external preparation placebo. | Drug: Treatment of MTX and HCQ<br>* Methotrexate: 10-15mg per week according to patient's weight, oral, for 24 weeks. Hydroxychloroquine: 200mg, 2 times a day, oral, for 24 weeks. Qingre Huoxue granule placebo: 10g, 2 times a day, oral, for 24 weeks. Qingre Huoxue external preparation placebo: 20g, 1 times a day, external, for 4 weeks, then 10g, 1 times a day, external, for 8 weeks.<br>* Other names: Treatment of MTX, HCQ and Qingre Huoxue placebo;|
| Experimental: Treatment of TCM<br>Patients were treated with oral Qingre Huoxue granule, Qingre Huoxue external preparation, methotrexate placebo and hydroxychloroquine placebo. | Drug: Treatment of TCM<br>* Qingre Huoxue granule: 10g, 2 times a day, oral, for 24 weeks. Qingre Huoxue external preparation: 20g, 1 times a day, external, for 4 weeks, then 10g, 1 times a day, external, for 8 weeks. Methotrexate placebo: 10-15mg per week according to patient's weight, oral, for 24 weeks. Hydroxychloroquine placebo: 200mg, 3 times a day, oral, for 24 weeks.<br>* Other names: Qingre Huoxue medicines，MTX placebo and HCQ placebo;|
| Experimental: Integrative Medicine<br>The patients were treated with methotrexate, hydroxychloroquine, oral Qingre Huoxue granule and Qingre Huoxue external preparation. | Drug: Integrative Medicine<br>* Qingre Huoxue granule: 10g, 2 times a day, oral, for 24 weeks. Qingre Huoxue external preparation: 20g, 1 times a day, external, for 4 weeks, then 10g, 1 times a day, external, for 8 weeks. Methotrexate: 10-15mg per week according to patient's weight, oral, for 24 weeks. Hydroxychloroquine: 200mg, 3 times a day, oral, for 24 weeks.<br>* Other names: Treatment of Qingre Huoxue medicines，MTX and HCQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from Baseline to week 24 in Disease Activity Score (DAS28) | Disease Activity Score for 28-joint counts was based on the erythrocyte sedimentation rate(ESR) (DAS28-4[ESR]) | 0 weeks, 12 weeks, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients achieving ACR20/50/70 | ACR20/50/70 is referred to American College of Rheumatology Criteria. | 0 week, 12 weeks, 24 weeks | 
| The change from baseline to week 24 in the score on the patient report outcome (PRO) | PRO scores ranges from 0 to 3, with higher scores indicating greater disability | 0 week, 12 weeks, 24 weeks | 
| The change in Sharp score | The change in X-Ray from baseline to week 52. | 0 week, 52 weeks | 
| The change in OMERACT RAMRIS score | The change in Magnetic Resonance Imaging from baseline to week 24. | 0 week, 24 weeks | 
| The number of adverse events | The number of adverse events that are related to treatment | 24 weeks |