Search / Trial NCT00001677

Methotrexate Alone Versus Combination of Methotrexate and Subcutaneous Fludarabine for Severe Rheumatoid Arthritis: Safety, Tolerance and Efficacy

Launched by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) · Dec 9, 2002

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Trial Information

Current as of March 02, 2024

Completed

Keywords

Immunosuppression Lymphocytes Magnetic Resonance Synovial Biopsy Synovitis Rheumatoid Arthritis

Description

The safety profile and efficacy of combination therapy will be evaluated using methotrexate (MTX) and the nucleoside analog fludarabine in 40 patients with severe refractory rheumatoid arthritis. The patients enrolled will be those who have experienced inadequate disease control with MTX alone or in combination with other immunosuppressive drugs such as sulfasalazine (SSZ), cyclosporin A (CsA), or hydroxychloroquine (HCQ). In this randomized, double-blind, placebo controlled trial, patients will be maintained on oral MTX at 17.5 mg/week to which either placebo or subcutaneous fludarabine at...

Gender

All

Eligibility criteria

  • Ability to provide informed consent to all aspects of the study after full information is provided.
  • Age equal to or older than 18.
  • A diagnosis of Rheumatoid Arthritis (RA) of more than 6 months as defined by the revised American College of Rheumatology criteria.
  • Active RA defined as: 6 or more swollen joints;
  • 6 or more tender joints;
  • ESR greater than 28 mm/hr (or CRP greater than 0.8) or morning stiffness greater than 45 minutes.
  • Incomplete response (defined as persistently active disease as described above) to treatment with at least one of the following regimens for over 3 months:
  • MTX alone (greater than or equal to 17.5 mg/week);
  • MTX (greater than or equal to 17.5 mg/week) plus HCQ (greater than or equal to 200 mg/day);
  • MTX (greater than or equal to 17.5 mg/week) plus SSZ (greater than or equal to 1 gm/d);
  • MTX (greater than or equal to 17.5 mg/week) plus CsA (1-3 mg/kg/day);
  • MTX (greater than or equal to 17.5 mg/week) plus SSZ (greater than 1 gm/day) plus HCQ (greater than or equal to 200 mg/day);
  • No requirement of corticosteroids in doses equivalent to over 10 mg/d prednisone nor other immunosuppressive agents required for the control of extraarticular manifestations at the time of study entry.
  • No active acute or chronic infections requiring antibiotic therapy, serious viral infections (such as hepatitis, herpes zoster, or HIV), or serious fungal infections. Patients with a positive PPD who have not received INH or other antituberculous therapy will be excluded.
  • No pregnant women, nursing mothers, or patients of childbearing age not practicing birth control.
  • No preexisting malignancy other than basal cell carcinoma.
  • No history of stroke, seizure disorder, or chronic neurologic disease.
  • No unstable coronary artery disease, cardiomyopathy, conduction heart block greater than first degree, or a dysrhythmia requiring therapy.
  • No confounding medical illness that in the judgment of the investigators would pose added risk for study participants (e.g., chronic hepatic, renal, or pulmonary disease or bone marrow hypoplasia).
  • No presence of seronegative spondyloarthropathy, systemic lupus erythematosus, systemic sclerosis, inflammatory myopathy, systemic vasculitis, psoriasis, or inflammatory bowel disease.
  • No serum creatinine greater than 2.0 mg/dL on at least 2 different occasions which is sustained for at least 1 month.
  • No hematocrit less than 28% (or hemoglobin less than 9.0 mg/dL), or platelet count less than 100,000, or white blood count less than 3,500/dL.
  • No patients with active lung disease, patients with a chronic and progressive lung disease, or patients with a chronic but stable lung disease with pulmonary function tests of less than 70% of predicted (DLCO less than 60%).
  • No patients with hypogammaglobulinemia (IgG count less than 300).
  • No patients treated with alkylating agents for over 1 year at any time or treated with a purine nucleoside analog at any time.

Attachments

readout_NCT00001677_2024-03-02.pdf

4.5 MB

NCT00001677_study_protocol.pdf

4.5 MB

About company

The National Institute of Allergy and Infectious Diseases (NIAID, /ˈnaɪ.æd/) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's mission is to conduct basic and applied research to better understand, treat, and prevent infectious, immunologic, and allergic diseases.

Contacts

JC

Jennifer Cobb

Immunology at National Institute of Allergy and Infectious Diseases (NIAID)

Locations

Bethesda, Maryland, United States

People applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

Reviews (48)

4.6

All reviews come from applied patients

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Leslie Alexander
20 September 2023

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Michael Foster
20 September 2023

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Dries Vincent
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

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