Triple III Comparison of Leflunomide Alone Versus Two DMARD Combinations in the Treatment of Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Leflunomide; Methotrexate-Sulfasalazine-Hydroxychloroquine; Leflunomide-Sulfasalazine-Hydroxychloroquine
Intervention description: A loading dose of 100 mg (or placebo) for three (3) days will be given. Following that three-day period, a dose of 20 mg/day will be maintained throughout the remainder of the study. This dose may be decreased to 10 mg/day at the discretion of the treating physician if minor toxicities occur (e.g., diarrhea, liver enzyme elevations; Methotrexate:
dosing starts at 10mg/week (4 tabs/wk). If total remission (according to ACR criteria found in Appendix II) has not been achieved and the labs are acceptable at the 8-week evaluation, the dose increased to 15 mg/week (6 tabs/wk);at the 16-week evaluation, the dose increased to 20 mg/week (8 tabs/wk). This dose will remain stable until the end of the study.
Sulfasalazine: dosing will start at 500 mg bid (1000 mg/day). This dose will remain steady until the 24-week evaluation. If total remission has not been achieved by this time and the labs remain acceptable,dose will be increased to 1000 mg bid (2000 mg/day) Hydroxychloroquine: dosing will be started and maintained throughout the study at 200 mg bid (400 mg/day).; Leflunomide: dose of 100 mg (or placebo) for three (3) days. Followed by a dose of 20 mg/day will be maintained throughout the remainder of the study. dose may be decreased to 10 mg/day at the discretion of the treating physician if minor toxicities occur Sulfasalazine: dosing will start at 500 mg bid (1000 mg/day). This dose will remain steady until the 24-week evaluation. If total remission has not been achieved by this time and the labs remain acceptable, dose will be increased to 1000 mg bid (2000 mg/day) Hydroxychloroquine: dosing will be started and maintained throughout the study at 200 mg bid (400 mg/day).
Intervention MeSH terms: Hydroxychloroquine; Sulfasalazine; Methotrexate; Leflunomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 69.0
Sex: All
Minimum age: 19 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The study has been designed as a 48-week, double-blind, randomized, controlled study
      comparing the use of leflunomide alone to combinations of leflunomide-sulfasalazine-HCQ, and
      methotrexate-sulfasalazine-HCQ.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age greater or 19 years and less than or 80 years old

          -  Duration of disease greater or equal to 6 months

          -  Diagnosis of RA with criteria

          -  Negative urine pregnancy test

          -  Be capable of understanding and giving written, voluntary informed consent

          -  Must present with at least six swollen and six tender joints at the screening
             evaluation

        Exclusion Criteria:

          -  Patients treated previously with leflunomide

          -  Patients that have been treated with methotrexate in combination with any of the study
             drugs

          -  Patients with a history of allergy to, or any history of significant clinical or
             laboratory adverse experience associated with any of the study drugs

          -  Doses of oral steroids that are either unstable or greater than 10mg/day

          -  Stage IV disease or other significant disease including chest x-rays that show
             evidence of rheumatoid lung disease. Stage IV disease is defined as x-ray evidence of
             cartilage/bone destruction with fibrous or bony ankylosis; creatinine greater than
             2.0mg/dL, AST or ALT greater normal

          -  Any significant liver, renal , hematologic, pulmonary, cardiovascular disease
             (including uncontrolled hypertension), any active peptic ulcer disease, or visual
             problems including a recent decrease in acuity, retinal disease, or macular
             degeneration

          -  Patients who are not willing to abstain from alcohol consumption

          -  Women of childbearing potential who are not practicing a successful method of
             contraception, or wish to become pregnant

          -  Patients that are unable to understand the study procedures and/or give written
             informed consent.