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Clinical Trial Evaluating Methotrexate + Biologic Versus Methotrexate, Salazopyrine and Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate (BIO 3)

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ClinicalTrials.gov Identifier: NCT02714634
Recruitment Status : Not yet recruiting
First Posted : March 21, 2016
Last Update Posted : March 21, 2016
Sponsor:
Information provided by (Responsible Party):
University Hospital, Strasbourg, France

Brief Summary:
Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted biologic therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate+salazopyrine+hydroxychloroquine could be an alternative option to biologics, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of biologics on triple therapy in methotrexate insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Insufficient Response to Methotrexate. Drug: Methotrexate + biologic administration Drug: methotrexate + salazopyrine + hydroxychloroquine administration Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 286 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Controlled Clinical Trial Evaluating Methotrexate + Biologic Versus Methotrexate, Salazopyrine and Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate
Study Start Date : March 2016
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: methotrexate + biologic group

Methotrexate +

biologic chosen by investigator

Drug: Methotrexate + biologic administration
  • Methotrexate + adalimumab or
  • Methotrexate + certolizumab or
  • Methotrexate + etanercept or
  • Methotrexate + golimumab or
  • Methotrexate + infliximab or
  • Methotrexate + abatacept or
  • Methotrexate + rituximab or
  • Methotrexate + tocilizumab

Active Comparator: Triple therapy
Triple therapy using 3 conventional disease modifying drugs (DMARDs)
Drug: methotrexate + salazopyrine + hydroxychloroquine administration



Primary Outcome Measures :
  1. Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone [ Time Frame: At 12 months ]

Secondary Outcome Measures :
  1. Serious adverse events rate [ Time Frame: At 3, 6, 9 and at 12 months ]
  2. Blood concentrations of hydroxychloroquine, salazopyrine and methotrexate in the triple therapy group and methotrexate, biologic and anti-drug antibody in the other group. [ Time Frame: at 6, and 12 months ]
  3. Clinical disease activity index (CDAI). [ Time Frame: At inclusion, 3, 6, 9 and 12 months ]
  4. DAS 28 CRP score. [ Time Frame: at inclusion, 3, 6, 9 and 12 months. ]
  5. 2010 ACR (American College of Rheumatology)/EULAR classification Criteria for RA, ACR 20, 50, 70 and boolean remission. [ Time Frame: at 3, 6, 9 and 12 months. ]
  6. Modified Sharp Van der Heijde score. [ Time Frame: at inclusion and at 12 months ]
  7. Change in comedications (dose) [ Time Frame: at 3, 6, 9 and 12 months ]
  8. Change in comedications (route of administration) [ Time Frame: at 3, 6, 9 and 12 months ]
  9. Change in comedications (drug) [ Time Frame: at 3, 6, 9 and 12 months ]
  10. QUALISEX score at inclusion, 6 months and at 12 months. [ Time Frame: at inclusion, 6 months and at 12 months. ]
  11. Medico-economic costs. [ Time Frame: at inclusion, 3, 6, 9 and at 12 months. ]
  12. Treatment compliance [ Time Frame: at 3, 6, 9 and 12 months ]
    A questionnaire will be filled by patient



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria
  • DAS28-CRP>3.2
  • Insufficient response to methotrexate at a weekly dose≥15mg after at least 3 months
  • RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)
  • Age greater or equal to 18 years
  • Written informed consent, dated and signed before initiating any trial-related procedure
  • Affiliation to a social insurance system
  • Women of child bearing potential, negative β-HCG assay (Human chorionic gonadotropin)
  • Effective method of birth control during the study and continuing 5 months after the end of the study for men and depending for the biotherapy associated for women (referred to the summary product characteristic).

Exclusion Criteria:

  • Previous treatment with one of the evaluated biologics
  • Previous treatment with triple therapy
  • Other inflammatory arthritis except RA associated with Sjögren's syndrome
  • Contraindication to all biologics or to methotrexate, sulfasalazine and hydroxychloroquine
  • Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion
  • Absence of tuberculosis screening
  • Patient who cannot be followed during 12 months
  • Pregnancy, breastfeeding, desire of pregnancy in the 12 months
  • Drug addiction, addiction to alcohol
  • Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment
  • Women of child bearing potential, unless they are using an effective method of birth control
  • Patient under law protection
  • Prisoners

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02714634


Contacts
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Contact: Jacques-Eric GOTTENBERG, Professor 3 88 12 79 53 ext +33 jacques-eric.gottenberg@chru-strasbourg.fr

Sponsors and Collaborators
University Hospital, Strasbourg, France

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Responsible Party: University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier: NCT02714634     History of Changes
Other Study ID Numbers: 6020
First Posted: March 21, 2016    Key Record Dates
Last Update Posted: March 21, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Hydroxychloroquine
Sulfasalazine
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents