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Corticosteroids and Anti TNF in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient

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ClinicalTrials.gov Identifier: NCT01724268
Recruitment Status : Unknown
Verified November 2012 by Hamad Medical Corporation.
Recruitment status was:  Recruiting
First Posted : November 9, 2012
Last Update Posted : November 9, 2012
Information provided by (Responsible Party):
Hamad Medical Corporation

Tracking Information
First Submitted Date  ICMJE November 7, 2012
First Posted Date  ICMJE November 9, 2012
Last Update Posted Date November 9, 2012
Study Start Date  ICMJE May 2012
Estimated Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2012)
Disease activity score [ Time Frame: 4 months ]
DAS 28: Disease activity score, is a modification of the original DAS score, it divides disease activity into high, moderate, low disease activity, and remission (High disease activity is DAS28 >5.1, moderate is DAS28 of >3.2 to 5.1, low disease activity is DAS28 of 2.6 to 3.2, and remission is DAS28 <2.6).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2012)
HAQ Score [ Time Frame: 4 months ]
HAQ Score: Health Assessment Questionnaire evaluates patients' ability to perform activities of daily living through their answers to 20 questions designed to assess upper or lower extremity use. These questions are organized into eight categories: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each question is answered on a four-level scale of impairment ranging from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; and 3 = inability to do.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Corticosteroids and Anti TNF in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient
Official Title  ICMJE Randomized Controlled Clinical Trial of Low Dose Corticosteroids vs Anti TNF Treatment in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient- a Pilot Study
Brief Summary

Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in the treatment of methotrexate inadequate responder rheumatoid arthritis patient.


Methotrexate + Prednisolone vs. Methotrexate + anti TNF

Detailed Description

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints and of the tissues around the joints, as well as in other organs in the body. Early diagnosis of rheumatoid arthritis and early aggressive treatment can help prevent joint damage, deformity and disability.

The management of RA rests on several principles; drug treatment, which comprise disease modifying anti-rheumatic drugs (DMARDS), but also non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs), as well as non-pharmacological measures, such as physical, occupational and psychological therapeutic approaches, together may lead to therapeutic success. However, the mainstay of RA treatment is the application of DMARDs. Methotrexate (MTX) is the anchor drug in the management of RA and has been used for many decades.

New and highly effective DMARDS have continued to emerge until the most recent years- in particular, biologic agents which target tumor necrosis factor, the interleukin 1 (IL -1) receptor, the IL-6 receptor, B lymphocytes and T cell co-stimulation. Furthermore, treatment strategies have changed during this period, initially by calling for early referral and early institution of DMARD treatment on the basis of respective evidence of clinical efficacy.

The EULAR (EUROPEAN LEAGUE AGAINST RHEUMATISM) recommendations for treatment of rheumatoid arthritis (3) emphasize that treatment should be aimed at reaching the target of remission or low disease activity (DAS 28 score ≤ 3.2) as soon as possible in every patient; as long as the target has not been reached, treatment should be adjusted by frequent (every 1-3 months) and strict monitoring.

MTX (1) should be part of the first treatment strategy in patients with active RA and when MTX contraindications (or intolerance) are present, other DMARDs should be considered.

GCs (1) added at low to moderately high doses to synthetic DMARD monotherapy (or combinations of synthetic DMARDs) provide benefit as initial short-term treatment, but should be tapered as rapidly as clinically feasible.

In a systematic review (4), GCs were found to be effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or combination therapy.

In patients responding insufficiently to MTX and/or other synthetic DMARDs with or without GCs, biological DMARDs should be started (1); current practice would be to start a TNF inhibitor (adalimumab, certolizumab, etanercept, golimumab or infliximab) which should be combined with MTX.

In most of the studies which included GCs in the management of RA, it was included at the beginning of the study (1).

In a recent trial (2), Inclusion of low-dose prednisone from the start into a two-year MTX-based tight control treatment strategy for early RA increases both effectiveness (i.e. disease activity variables) and outcome (i.e. erosive joint damage) without increasing toxicity. It also reduces the need for (early) treatment with biologicals.

The anti TNF treatment is expensive and carries the risk of infection. To our knowledge, there is no study comparing the addition of small doses of steroids of steroids to the addition of anti TNF in patients who failed or did not tolerate the 25 mg of MTX.

The investigators have designed this study to compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in patients who did not achieve remission on maximum tolerated MTX dose (up to 25 mg).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Intervention  ICMJE
  • Drug: Pred + Meth
    PREDNISOLONE 10mg orally ONCE DAILY and Methotrexate 25 mg / day
    Other Names:
    • Prednisolone
    • Methotrexate
  • Drug: Anti TNF + Meth
Study Arms  ICMJE
  • Experimental: Pred + Meth

    Prednisolone : 10 mg daily

    + Methotrexate : 25 mg/ day

    ARM 1 Treatment Arm

    Intervention: Drug: Pred + Meth
  • Active Comparator: Anti TNF + Meth

    Etanrcept: 50 mg; Adalimumab: 40 mg; Infliximab: 3mg/kg

    + Methotrexate 25 mg per day Control Arm

    Intervention: Drug: Anti TNF + Meth
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 8, 2012)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2014
Estimated Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males or females aged 18 years or older.
  2. Satisfies the 2010 American College of Rheumatology/European League Against Rheumatism Criteria for Rheumatoid Arthritis.
  3. Rheumatoid arthritis of < 2 years duration
  4. Has active disease at the time of enrollment. (Modified Disease Activity Score ≥ 3.2)
  5. Demonstrates functional status of class I, II, or III as defined by American College of Rheumatology revised criteria.
  6. Is on methotrexate 25 mg weekly or the maximum tolerated dose, therapy should be for at least 3 months duration and on the highest tolerated dose for the last 4 weeks.
  7. Is able and willing to self-inject study drug if assigned to the injectable drug group or have a designee who can do so.
  8. Is PPD negative (skin test for TB exposure) or completed ≥1 month of latent TB treatment if PPD ≥ 5 or quantiferon (blood test for TB exposure) positive.
  9. Is having normal Chest X-Ray.
  10. Is Hepatitis B Negative.
  11. Not on NSAID (e.g. Ibuprofen) or receiving the same dose of the same NSAID throughout the study period unless side effects occur
  12. All patients in childbearing age should use effective birth control methods
  13. Is capable of understanding and signing an informed consent form.

Exclusion Criteria:

  1. Received any previous treatment with Tumor Necrosis Factor inhibitor or other biologic treatments for Rheumatoid Arthritis (such as abatacept, rituximab, tocilizumab, or Anakinra).
  2. Received any previous treatment with oral corticosteroids (e.g. prednisolone)
  3. Has a known or expected allergy, contraindication, or hypersensitivity to the medications tested.
  4. Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in, and completion of, the study, or could preclude the evaluation of the subject's response.
  5. Received any of the following within 4 weeks before baseline visit: leflunomide, hydroxychloroquine, chloroquine, cyclosporine, sulphasalazine, auranofin, intramuscular gold, azathioprine, minocycline, or D-penicillamine
  6. Received cyclophosphamide within 6mths before screening visit.
  7. Received any live (attenuated) vaccines within 4 weeks before screening visit.
  8. Received intra-articular or subcutaneous corticosteroid injection within 4 weeks before screening visit.
  9. Received bolus intramuscular/ intravenous treatment with corticosteroids (> 20mg prednisone or equivalent) within 4 weeks before screening visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Qatar
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01724268
Other Study ID Numbers  ICMJE 11224-12
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hamad Medical Corporation
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hamad Medical Corporation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: MAGDI H ABDELRAHMAN, MBBS Hamad Medical Corporation
Principal Investigator: MOHAMMED M HAMMOUDEH, MD Hamad Medical Corporation
PRS Account Hamad Medical Corporation
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP