Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)

This study has been completed.
Sponsor:
Collaborators:
Amgen
Barr Laboratories
Pfizer
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00259610
First received: November 28, 2005
Last updated: July 16, 2014
Last verified: October 2013
  Purpose

The purpose of this study is to 1)to determine if it is better to treat all early RA patients with methotrexate in combination with hydroxychloroquine plus sulfasalazine or in combination with etanercept or reserve this treatment for patients who do not appropriately respond to methotrexate alone and 2) to determine which combination of methotrexate therapy is better


Condition Intervention Phase
Rheumatoid Arthritis
Drug: methotrexate
Drug: sulfasalazine
Drug: hydroxychloroquine
Drug: etanercept
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Disease Activity Score Erythrocyte Sedimentation Rate(DAS28-ESR) [ Time Frame: Change of the Mean of DAS28-ESR between weeks 48 - 102. ] [ Designated as safety issue: No ]

    Outcome measured was the observed-group analysis of the DAS28-ESR between weeks 48 and 102. DAS28 is a calculated scale using a formula that includes the number of tender joints and swollen joints (28 joints maximum). The following is the calculation: DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH. The ESR is the rate at which red blood cells sediment in a period of one hour.

    The total range for the DAS28ESR goes from 0.0 to 9.2; this indicates the current activity of the rheumatoid arthritis of a subject. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity.



Secondary Outcome Measures:
  • Radiographic Disease Progression Between Baseline and Week 102 as Assessed by Van Der Heijde Modified Sharp Scores. [ Time Frame: Year 2, Week 102 ] [ Designated as safety issue: No ]
    Changes in disease progression between treatment groups will be described by the mean score at two years as assessed after adjustment for the baseline radiographic score. Radiographs were observed of hands, wrists, and feet. The range of scores available for the modified Sharp Score is 0 to 448. The erosion score per joint of the hands can range from 0 to 5. The maximal erosion score for each hand is thus 80, considering the 16 areas for erosions per hand. Joint space narrowing and joint subluxation or luxation are combined in a single score with a range of 0 to 4 with a max score of 60. The erosion score per joint can range from 0 to 10, with each side of the joint independently scored from 0 to 5. The maximal erosion score per foot is thus 60. The joint space narrowing and joint (sub)luxation are combined in a single score with a range of 0 to 4. The maximal narrowing/(sub)luxation score per foot is thus 24.


Enrollment: 755
Study Start Date: May 2004
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
methotrexate (MTX) + etanercept
Drug: methotrexate
varies
Drug: etanercept
varies
Active Comparator: 2
methotrexate (MTX) + sulfasalazine (SSZ)/hydroxychloroquine (HCQ)
Drug: methotrexate
varies
Drug: sulfasalazine
varies
Drug: hydroxychloroquine
varies
Active Comparator: 3
methotrexate (MTX) or MTX + Etanercept
Drug: methotrexate
varies
Drug: etanercept
varies
Active Comparator: 4
methotrexate (MTX) or MTX + sulfasalazine (SSZ)/hydroxychloroquine (HCQ)
Drug: methotrexate
varies
Drug: sulfasalazine
varies
Drug: hydroxychloroquine
varies

Detailed Description:

The ultimate goal of RA is to eliminate symptoms, restoring the patient to normal physical, social, emotional, and vocational function, and preserving the structure and integrity of joints. While disease modifying anti-rheumatic drugs (DMARDs) have long been the cornerstone of RA therapy, the limitations of DMARDs have become increasingly apparent and investigators continue to gain insight into the pathogenesis of this disease. Recent evidence suggests that treatment earlier in the disease process with more aggressive approaches results in superior long-term outcomes compared to less intensive treatment regimens. Specifically, there is growing interest in the possibility that early "aggressive" treatment with combinations of DMARDs as initial treatment in efforts to potentially reduce the proportion of patients that advance to severe disability.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a diagnosis of RA for less than or equal to 3 years
  • Be 18 years of age or older at the time of diagnosis

Exclusion Criteria:

  • Pregnant or lactating women
  • History of chronic infection, such as hepatitis, pneumonia, or chronic skin infections
  • Active TB or evidence of latent TB
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00259610

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Amgen
Barr Laboratories
Pfizer
Investigators
Principal Investigator: Jeffrey Curtis, MD University of Alabama at Birmingham
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00259610     History of Changes
Other Study ID Numbers: X031030004, 20040391
Study First Received: November 28, 2005
Results First Received: May 31, 2012
Last Updated: July 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
RA
painful joints
swollen joints

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Hydroxychloroquine
TNFR-Fc fusion protein
Sulfasalazine
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal

ClinicalTrials.gov processed this record on September 18, 2014