Triple III Comparison of Leflunomide Alone Versus Two DMARD Combinations in the Treatment of Rheumatoid Arthritis

NCT00579878 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 0012-01-FB
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Measuring the Safety and Efficacy of a New DMARD, Leflunomide Alone or in Combination With Traditional DMARD's. Participants Reaching ACR 20 Response. at 48 Weeks

  The combination of Methotrexate-Sulfasalazine-Hydroxychloroquine has been shown to be more effective than Methotrexate alone or the double combination of Methotrexate-Hydroxychloroquine. Primary outcome is ACR 20 response at 48 weeks. An ACR 20 Response is a measure of at least 20% improvement in the number of tender and swollen joints. and a 20% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function; the physician's global assessment of disease status; serum C-reactive protein levels.

  48 weeks

Study Arms (3)

Leflunomide alone vs combination therapy

ACTIVE COMPARATOR

Group A: Leflunomide alone

Drug: Leflunomide

Methotrexate-Sulfasalazine-Hydroxychloroquine

ACTIVE COMPARATOR

Methotrexate, Sulfasalazine, Hydroxychloroquine.

Drug: Methotrexate-Sulfasalazine-Hydroxychloroquine

Leflunomide-Sulfasalazine-Hydroxychloroquine

ACTIVE COMPARATOR

Leflunomide-Sulfasalazine-Hydroxychloroquine

Drug: Leflunomide-Sulfasalazine-Hydroxychloroquine

Interventions

Leflunomide DRUG

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

Also known as: Arava®

Leflunomide alone vs combination therapy

Methotrexate-Sulfasalazine-Hydroxychloroquine DRUG

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).

Also known as: Trexall, Rheumatrex, Azulfidine®, Plaquenil®

Methotrexate-Sulfasalazine-Hydroxychloroquine

Leflunomide-Sulfasalazine-Hydroxychloroquine DRUG

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).

Also known as: Arava®, Azulfidine®, Plaquenil®

Leflunomide-Sulfasalazine-Hydroxychloroquine

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 69198-3025, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Leflunomide; Methotrexate; Sulfasalazine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Chloroquine; Aminoquinolines; Quinolines

Results Point of Contact

• Title: James O'Dell
• Organization: University of Nebraska Medical Center

jrodell@unmc.edu

402 559-7288

Study Officials

• James R O'Dell, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 24, 2007
• Study Start: March 27, 2001
• Primary Completion: March 11, 2010
• Study Completion: March 11, 2010
• Last Updated: October 2, 2023
• Results First Posted: May 14, 2019

Record last verified: 2023-09

Locations

US (1)