Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: methotrexate
* Drug: sulfasalazine
* Drug: hydroxychloroquine
* Drug: etanercept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>methotrexate (MTX) + etanercept | Drug: methotrexate<br>* varies<br>Drug: etanercept<br>* varies<br>|
| Active Comparator: 2<br>methotrexate (MTX) + sulfasalazine (SSZ)/hydroxychloroquine (HCQ) | Drug: methotrexate<br>* varies<br>Drug: sulfasalazine<br>* varies<br>Drug: hydroxychloroquine<br>* varies<br>|
| Active Comparator: 3<br>methotrexate (MTX) or MTX + Etanercept | Drug: methotrexate<br>* varies<br>Drug: etanercept<br>* varies<br>|
| Active Comparator: 4<br>methotrexate (MTX) or MTX + sulfasalazine (SSZ)/hydroxychloroquine (HCQ) | Drug: methotrexate<br>* varies<br>Drug: sulfasalazine<br>* varies<br>Drug: hydroxychloroquine<br>* varies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score Erythrocyte Sedimentation Rate(DAS28-ESR) | 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. | Change of the Mean of DAS28-ESR between weeks 48 - 102. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Disease Progression Between Baseline and Week 102 as Assessed by Van Der Heijde Modified Sharp Scores. | 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. | Year 2, Week 102 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA, painful joints, swollen joints