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

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

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.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Treatment of MTX and HCQ; Drug: Treatment of TCM; Drug: Integrative Medicine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 468
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Bei Jing, Beijing, China, 100052
      • Guang'anmen hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment of MTX and HCQ; 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; 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.; Other Names: Treatment of MTX, HCQ and Qingre Huoxue placebo
Experimental: Treatment of TCM; Patients were treated with oral Qingre Huoxue granule, Qingre Huoxue external preparation, methotrexate placebo and hydroxychloroquine placebo.	Drug: Treatment of TCM; 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.; Other Names: Qingre Huoxue medicines，MTX placebo and HCQ placebo
Experimental: Integrative Medicine; The patients were treated with methotrexate, hydroxychloroquine, oral Qingre Huoxue granule and Qingre Huoxue external preparation.	Drug: Integrative Medicine; 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.; Other Names: Treatment of Qingre Huoxue medicines，MTX and HCQ

What is the study measuring?

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 number of adverse events	The number of adverse events that are related to treatment	24 weeks
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

Collaborators and Investigators

• Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Publications and helpful links

General Publications

• Gong X, Liu WX, Tang XP, Wang J, Liu J, Huang QC, Liu W, Fang YF, He DY, Liu Y, Gao ML, Wu QJ, Chen S, Li ZB, Wang Y, Xie YM, Zhang JL, Zhou CY, Ma L, Wang XC, Zhang C, Jiang Q. Traditional Chinese Medicine Qingre Huoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis: A Multicenter, Double-Blind, Randomized Controlled Trial. Front Pharmacol. 2021 May 25;12:679588. doi: 10.3389/fphar.2021.679588. eCollection 2021.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 26, 2015
• First Submitted That Met QC Criteria: September 15, 2015
• First Posted (Estimate): September 16, 2015

Study Record Updates

• Last Update Posted (Estimate): June 20, 2016
• Last Update Submitted That Met QC Criteria: June 17, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 2013BAI02B06