Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Agentschap voor Innovatie door Wetenschap en Technologie
Information provided by (Responsible Party):
P. Verschueren, Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier:
NCT01172639
First received: July 28, 2010
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

The Combinatietherapie Bij Reumatoide Artritis (CoBRA) trial was a milestone in the development of the present treatment paradigm for Rheumatoid Arthritis (RA). This study introduced the principle of fast remission induction by means of a combination of standard Disease Modifying AntiRheumatic Drugs (DMARDs) and a step down bridge therapy with high dose glucocorticoids in early Rheumatoid Arthritis.

The purpose of the present study is to compare different combinations of traditional DMARDs and glucocorticoids, based on the original CoBRA protocol, for treatment of early Rheumatoid Arthritis.

Besides the efficacy and effectiveness of these strategies, patient centered outcomes and potential implementation problems of such treatment strategies are evaluated.


Condition Intervention Phase
Rheumatoid Arthritis
Other: randomisation
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 2 Year Prospective Multicentre Randomised Controlled Trial Comparing Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.

Resource links provided by NLM:


Further study details as provided by Universitaire Ziekenhuizen Leuven:

Primary Outcome Measures:
  • remission [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    proportion in remission defined by a Disease Activity Score based on the 28 joint count (DAS28)

  • remission [ Time Frame: week 52 ] [ Designated as safety issue: No ]
    proportion in remission defined by a DAS28 (co-primary end point)

  • remission [ Time Frame: week 104 ] [ Designated as safety issue: No ]
    proportion in remission defined by a DAS28 (co-primary end point)


Secondary Outcome Measures:
  • efficacy [ Time Frame: week 16 ] [ Designated as safety issue: No ]

    efficacy as defined by:

    • Disease activity: proportion responders according to the criteria of the European League Against Rheumatism (EULAR)
    • Functionality: proportion Clinically Meaningfull (CM) Health Assessment Questionnaire (HAQ) responders and proportion HAQ = 0

  • effectiveness [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    • Proportion of treatment failures due to efficacy/effectiveness problems
    • Proportion with unplanned treatment changes
    • Proportion lost from follow up
    • Total cumulative steroid dose / mean steroid dose per day
    • Proportion started on biologics

  • safety [ Time Frame: up to week 104 ] [ Designated as safety issue: Yes ]
    number and type of (serious) adverse events

  • efficacy [ Time Frame: week 28 ] [ Designated as safety issue: No ]

    efficacy as defined by:

    • Disease activity: proportion EULAR responders
    • Functionality: proportion CM HAQ responders and proportion HAQ = 0
    • radiographical score

  • efficacy [ Time Frame: week 52 ] [ Designated as safety issue: No ]

    efficacy as defined by:

    • Disease activity: proportion EULAR responders
    • Functionality: proportion CM HAQ responders and proportion HAQ = 0
    • radiographical score

  • efficacy [ Time Frame: week 104 ] [ Designated as safety issue: No ]

    efficacy as defined by:

    • Disease activity: proportion EULAR responders
    • Functionality: proportion CM HAQ responders and proportion HAQ = 0
    • radiographical score

  • effectiveness [ Time Frame: week 52 ] [ Designated as safety issue: No ]
    • Proportion of treatment failures due to efficacy/effectiveness problems
    • Proportion with unplanned treatment changes
    • Proportion lost from follow up
    • Total cumulative steroid dose / mean steroid dose per day
    • Proportion started on biologics

  • effectiveness [ Time Frame: week 104 ] [ Designated as safety issue: No ]
    • Proportion of treatment failures due to efficacy/effectiveness problems
    • Proportion with unplanned treatment changes
    • Proportion lost from follow up
    • Total cumulative steroid dose / mean steroid dose per day
    • Proportion started on biologics


Estimated Enrollment: 400
Study Start Date: February 2009
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
CoBRA classic high risk group
  • Methotrexate (MTX)
  • Sulphasalazine
  • Step down steroid full dose
Other: randomisation
Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
CoBRA slim high risk group
  • MTX
  • Step down steroid half dose
Other: randomisation
Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
CoBRA avant-garde high risk group
  • MTX
  • Leflunomide
  • Step down steroid half dose
Other: randomisation
Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
CoBRA slim low risk group
  • MTX
  • Step down steroid half dose
Other: randomisation
Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
Tight Step Up low risk group
  • MTX
  • No additional oral steroids allowed
Other: randomisation
Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of RA as defined by the 1987 revised American College of Rheumatology (ACR) criteria
  • Early RA (less than 1 year)
  • Use a reliable method of contraception for women of childbearing potential
  • Able and willing to give written informed consent and participate in the study

Exclusion Criteria:

  • Previous treatment with DMARDs
  • Previous treatment with oral corticosteroids at a dosage of more than 10 milligrams (mg) prednisone within 4 weeks before baseline
  • Previous treatment with oral corticosteroids at a dosage equal to or less than 10 mg prednisone within 2 weeks before baseline
  • Previous treatment with oral corticosteroids for more than 4 weeks
  • Previous treatment with Intra Articular corticosteroids within 4 weeks before baseline
  • Previous treatment with an investigational drug for the treatment or prevention of RA
  • Contraindications for corticosteroids
  • Contraindications for DMARDs
  • Psoriatic Arthritis
  • Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
  • Pregnancy, breastfeeding or no use of a reliable method of contraception
  • Alcohol or drug abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01172639

Locations
Belgium
OLV Ziekenhuis
Aalst, Belgium, 9300
ASZ
Aalst, Belgium, 9300
Imelda Ziekenhuis
Bonheiden, Belgium, 2820
AZ St Lucas
Brugge, Belgium, 8310
Reumacentrum
Genk, Belgium, 3600
Reuma praktijk
Genk, Belgium, 3600
UZ Gent, dept. of Rheumatology
Gent, Belgium, 9000
Reumapraktijk
Hasselt, Belgium, 3500
Reuma instituut Hasselt
Hasselt, Belgium, 3500
Jan Yperman Ziekenhuis
Ieper, Belgium, 8900
AZ groeninge
Kortrijk, Belgium, 8500
HHart Ziekenhuis
Leuven, Belgium, 3000
Universitaire Ziekenhuizen Leuven
Leuven, Belgium, 3000
MCH
Leuven, Belgium, 3000
AZ St maarten
Mechelen, Belgium, 2800
ZNA Jan Palfijn
Merksem, Belgium, 2170
Henri Serruys ziekenhuis
Oostende, Belgium, 8400
Sponsors and Collaborators
P. Verschueren
Agentschap voor Innovatie door Wetenschap en Technologie
Investigators
Principal Investigator: Patrick Verschueren, MD, PhD Universitaire Ziekenhuizen Leuven
  More Information

Publications:

Responsible Party: P. Verschueren, Prof. Dr., Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT01172639     History of Changes
Other Study ID Numbers: CareRA, 2008-007225-39
Study First Received: July 28, 2010
Last Updated: January 28, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Universitaire Ziekenhuizen Leuven:
CoBRA

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 16, 2014