Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) (TEAR)

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ClinicalTrials.gov Identifier: NCT00259610

Recruitment Status : Completed

First Posted : November 29, 2005

Results First Posted : July 17, 2014

Last Update Posted : July 17, 2014

Sponsor:

Collaborators:

Amgen

Barr Laboratories

Pfizer

Information provided by (Responsible Party):

University of Alabama at Birmingham

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: methotrexate Drug: sulfasalazine Drug: hydroxychloroquine Drug: etanercept	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	755 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
Study Start Date :	May 2004
Actual Primary Completion Date :	June 2009
Actual Study Completion Date :	June 2009

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Rheumatoid arthritis

MedlinePlus related topics: Arthritis Rheumatoid Arthritis Tears

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

Disease Activity Score Erythrocyte Sedimentation Rate(DAS28-ESR) [ Time Frame: Change of the Mean of DAS28-ESR between weeks 48 - 102. ]
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 ]
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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00259610

Locations

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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

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Principal Investigator:	Jeffrey Curtis, MD	University of Alabama at Birmingham

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications of Results:

Moreland LW, O'Dell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW, Bridges SL Jr, Zhang J, McVie T, Howard G, van der Heijde D, Cofield SS; TEAR Investigators. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012 Sep;64(9):2824-35. doi: 10.1002/art.34498.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Charles-Schoeman C, Yin Lee Y, Shahbazian A, Wang X, Elashoff D, Curtis JR, Navarro-Millán I, Yang S, Chen L, Cofield SS, Moreland LW, Paulus H, O'Dell J, Bathon J, Louis Bridges S Jr, Reddy ST. Improvement of High-Density Lipoprotein Function in Patients With Early Rheumatoid Arthritis Treated With Methotrexate Monotherapy or Combination Therapies in a Randomized Controlled Trial. Arthritis Rheumatol. 2017 Jan;69(1):46-57. doi: 10.1002/art.39833.

Hwang YG, Balasubramani GK, Metes ID, Levesque MC, Bridges SL Jr, Moreland LW. Differential response of serum amyloid A to different therapies in early rheumatoid arthritis and its potential value as a disease activity biomarker. Arthritis Res Ther. 2016 May 17;18(1):108. doi: 10.1186/s13075-016-1009-y.

Charles-Schoeman C, Wang X, Lee YY, Shahbazian A, Navarro-Millán I, Yang S, Chen L, Cofield SS, Moreland LW, O'Dell J, Bathon JM, Paulus H, Bridges SL Jr, Curtis JR. Association of Triple Therapy With Improvement in Cholesterol Profiles Over Two-Year Followup in the Treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheumatol. 2016 Mar;68(3):577-86. doi: 10.1002/art.39502.

Maska LB, Sayles HR, O'Dell JR, Curtis JR, Bridges SL Jr, Moreland LW, Cofield SS, Mikuls TR. Serum cotinine as a biomarker of tobacco exposure and the association with treatment response in early rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 Dec;64(12):1804-10. doi: 10.1002/acr.21758.

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Responsible Party:	University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT00259610
Other Study ID Numbers:	X031030004 20040391
First Posted:	November 29, 2005 Key Record Dates
Results First Posted:	July 17, 2014
Last Update Posted:	July 17, 2014
Last Verified:	October 2013

Keywords provided by University of Alabama at Birmingham:


RA painful joints swollen joints

Additional relevant MeSH terms:

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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Hydroxychloroquine Sulfasalazine Etanercept Methotrexate Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents	Physiological Effects of Drugs 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 Antimalarials Antiprotozoal Agents Antiparasitic Agents

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