Disease-Modifying Antirheumatic Drugs Cycle Combination Therapy Research (DCCT)

A 48-week, Multi-center, Randomized, Open-lable, Controlled Study to Assess the Response (ACR20) Using Different Disease-Modifying Antirheumatic Drugs Cycle Combination Regimen in Adult Patients With Active Rheumatoid Arthritis

This study was intended to assess the efficacy and safety of different Disease-Modifying Antirheumatic Drugs cycle combination regimen using the American College of Rheumatology (ACR) criteria of 20% improvement in symptoms (ACR20) in managing active adult rheumatoid arthritis.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: leflunomide; Drug: methotrexate

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanxi
    • TaiYuan, Shanxi, China, 030001
      • Recruiting
      • rheumatism department,Second hospital of Shanxi medical university
      • Contact: li xiao feng; Phone Number: 086-0351-3074231; Email: lixiaofeng_sxey@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

RA patients：

• Male and female patients aged 18 - 75 years (inclusive).
• Body weight between 50 and 100 kg (inclusive).
• Post menopausal or surgically sterile female patients are allowed. Female patients of child-bearing potential may participate if they are already on a stable dose of methotrexate. Additional birth control details to be provided at screening. Male patients must use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
• Diagnosis of RA, classified by American Rheumatism Association 1987 revised criteria.
• Active disease evaluation (DAS 28 > 3.2).
• Patients who using steroids before enrollment, the dose should not be more than 30mg/d, and remain unchanged for more than 30days.
• Without use of other disease activity controlling drugs.
• Get the informed consent.

Exclusion Criteria:

• Advanced patients with severe joints disability.
• Pregnant or breast- feeding female patients.
• Patients with severe primary disease or impairment of heart, brain, lung, liver (ALT or AST > 1.5 normal value), kidney (sCr > normal value), endocrine, and hematology system.
• Concomitant with other rheumatic disease.
• Alcohol taken or drug abusing patients.
• Patients with congestive heart failure, QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded.
• Patients who have received intra-articular or systemic corticosteroid injections having been required for treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4 weeks prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: leflunomide; Leflunomide 10-20 mg/d	Drug: leflunomide; Leflunomide 10-20 mg, orally, once daily for up to 48 weeks. Twelve weeks after the initial Leflunomide induction, patients were randomized into two groups (LEF+CTX:LEF+MTX=2:1) if the DAS 28 were higher than 2.6, or continuing leflunomide use without dosing change. Then, the disease activity was assessed using DAS 28 every 12 weeks. The regimen should remain unchanged if the DAS 28 reached to less than 2.6, otherwise, a third (24 weeks) or fourth (36 weeks) DMARs should be added. Intravenous CTX was administrated once 200-400mg per 3 weeks.
Active Comparator: methotrexate; MTX 7.5-15 mg/week	Drug: methotrexate; MTX 7.5-15 mg, orally, once weekly for up to 48 weeks. Twelve weeks after the initial MTX induction, patients were randomized into two groups (MTX+CTX:LEF+MTX=2:1) if the DAS 28 were higher than 2.6, or continuing MTX use without dosing change. Then, the disease activity was assessed using DAS 28 every 12 weeks. The regimen should remain unchanged if the DAS 28 reached to less than 2.6, otherwise, a third (24 weeks) or fourth (36 weeks) DMARs should be added. Intravenous CTX was administrated once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20	Percentage of subjects who meet the response rate of ACR20 at each post-dose visit	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR50	Percentage of subjects who meet the response rate of ACR 50 at week 48	48 weeks
ACR70	Percentage of subjects who meet the response rate of ACR 70 at week 48	48week
EULAR response：good response	Percentage of subjects who meet the EULAR response criteria of good response at week 48	48 week
EULAR response ：moderate response	Percentage of subjects who meet the EULAR response criteria of moderate response at week 48	48 week

Collaborators and Investigators

• Sponsor: Shanxi Medical University
• Investigators: Principal Investigator: li xiao feng, Second Hospital of Shanxi Medical University

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): May 1, 2014

Study Registration Dates

• First Submitted: May 28, 2012
• First Submitted That Met QC Criteria: June 11, 2012
• First Posted (Estimate): June 12, 2012

Study Record Updates

• Last Update Posted (Estimate): June 14, 2012
• Last Update Submitted That Met QC Criteria: June 12, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Methotrexate; RA; Leflunomide
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Leflunomide
• Other Study ID Numbers: DMARD-RA