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

January 8, 2019 updated by: P. Verschueren

A 2 Year Prospective Multicentre Randomised Controlled Trial Comparing Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium, 9300
        • ASZ
      • Aalst, Belgium, 9300
        • OLV Ziekenhuis
      • Bonheiden, Belgium, 2820
        • Imelda Ziekenhuis
      • Brugge, Belgium, 8310
        • AZ St Lucas
      • Genk, Belgium, 3600
        • Reuma praktijk
      • Genk, Belgium, 3600
        • Reumacentrum
      • Gent, Belgium, 9000
        • UZ Gent, dept. of Rheumatology
      • Hasselt, Belgium, 3500
        • Reuma Instituut Hasselt
      • Hasselt, Belgium, 3500
        • Reumapraktijk
      • Ieper, Belgium, 8900
        • Jan Yperman ziekenhuis
      • Kortrijk, Belgium, 8500
        • AZ Groeninge
      • Leuven, Belgium, 3000
        • Universitaire Ziekenhuizen Leuven
      • Leuven, Belgium, 3000
        • HHart Ziekenhuis
      • Leuven, Belgium, 3000
        • MCH
      • Mechelen, Belgium, 2800
        • AZ St maarten
      • Merksem, Belgium, 2170
        • ZNA Jan Palfijn
      • Oostende, Belgium, 8400
        • Henri Serruys ziekenhuis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of RA as defined by the 1987 or 2010 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: CoBRA classic high risk group
  • Methotrexate 15mg tablet by mouth, weekly for entire trial
  • Sulfasalazine 2g tablet by mouth, daily for 40 weeks
  • Prednisone tablet by mouth, weekly step down scheme 60 - 40 - 25 - 20 - 15 - 10 mg daily for 6 weeks, followed by 7.5mg daily till week 28, then further tapered down to stop at week 32
Drug: Methotrexate
Methotrexate tablet
Other Names:
  • Ledertrexate
Drug: Sulfasalazine
Sulfasalazine tablet
Other Names:
  • Salazopyrine
Drug: Prednisone
Prednisone tablet
Other: CoBRA slim high risk group
  • Methotrexate 15mg tablet by mouth, weekly for entire trial
  • Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
Drug: Methotrexate
Methotrexate tablet
Other Names:
  • Ledertrexate
Drug: Prednisone
Prednisone tablet
Other: CoBRA avant-garde high risk group
  • Methotrexate 15mg tablet by mouth, weekly for 40 weeks (continued for entire trial if randomized to Methotrexate monotherapy at week 40)
  • Leflunomide 10mg tablet by mouth, daily for 40 weeks (continued for entire trial if randomized to Leflunomide monotherapy at week 40)
  • Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
Drug: Methotrexate
Methotrexate tablet
Other Names:
  • Ledertrexate
Drug: Prednisone
Prednisone tablet
Drug: Leflunomide
Leflunomide tablet
Other Names:
  • Arava
Other: CoBRA slim low risk group
  • Methotrexate 15mg tablet by mouth, weekly for entire trial
  • Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
Drug: Methotrexate
Methotrexate tablet
Other Names:
  • Ledertrexate
Drug: Prednisone
Prednisone tablet
Other: Tight Step Up low risk group
  • Methotrexate 15mg tablet by mouth, weekly for entire trial
  • No oral steroids allowed during the first year of the trial
Drug: Methotrexate
Methotrexate tablet
Other Names:
  • Ledertrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission According to DAS28-CRP at Week 16
Time Frame: week 16

Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 16.

DAS28-CRP is calculated with the following formula : 0.56*SQRT TJC28+0.28*SQRT SJC28+0.36*ln (CRP+1)+0.014*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS).

A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity.
week 16
Remission According to DAS28-CRP at Week 52
Time Frame: week 52

Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 52. (co-primary end point)

DAS28-CRP is calculated with the following formula : 0.56*SQRT TJC28+0.28*SQRT SJC28+0.36*ln (CRP+1)+0.014*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS).

A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity.
week 52
Remission According to DAS28-CRP at Week 104
Time Frame: week 104

Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 104. (co-primary endpoints)

DAS28-CRP is calculated with the following formula : 0.56*SQRT TJC28+0.28*SQRT SJC28+0.36*ln (CRP+1)+0.014*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS).

A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity.
week 104

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission According to SDAI (Simple Disease Activity Index) at Week 16
Time Frame: week 16

Number of patients in remission according to SDAI (Simplified Disease Activity Index) at week 16.

SDAI is calculated with the following formula : TJC28+SJC28+GH+GA ph in which TJC is the number of tender joints, SJC the number of Swollen Joint and GH the general health assessed by the patient on a Visual Analogue Scale (VAS) and GA ph the general assessment of the physician on a VAS.

A value below 3.3 is indicating remission, between 3.4 and 11.0 low disease activity, between 11.1 and 26.0 moderate disease activity and above 26.0 high disease activity.
week 16
Remission According to SDAI at Week 52
Time Frame: week 52

Number of patients in remission according to SDAI (Simplified Disease Activity Index) at week 52.

SDAI is calculated with the following formula : TJC28+SJC28+GH+GA ph in which TJC is the number of tender joints, SJC the number of Swollen Joint and GH the general health assessed by the patient on a Visual Analogue Scale (VAS) and GA ph the general assessment of the physician on a VAS.

A value below 3.3 is indicating remission, between 3.4 and 11.0 low disease activity, between 11.1 and 26.0 moderate disease activity and above 26.0 high disease activity.
week 52
Remission According to SDAI at Week 104
Time Frame: week 104

Number of patients in remission according to SDAI (Simplified Disease Activity Index) at week 104.

SDAI is calculated with the following formula : TJC28+SJC28+GH+GA ph in which TJC is the number of tender joints, SJC the number of Swollen Joint and GH the general health assessed by the patient on a Visual Analogue Scale (VAS) and GA ph the general assessment of the physician on a VAS.

A value below 3.3 is indicating remission, between 3.4 and 11.0 low disease activity, between 11.1 and 26.0 moderate disease activity and above 26.0 high disease activity.
week 104
Clinically Significant Change in HAQ Score
Time Frame: Baseline-week104

Number of patients with a change of > 0.22 in the Health Assessment Questionnaire (HAQ) score over the period between baseline and week 104.

A change of > 0.22 in this score is considered as clinical relevant for rheumatoid arthritis patients.
Baseline-week104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

P. Verschueren

Collaborators

Agentschap voor Innovatie door Wetenschap en Technologie

Investigators

  • Principal Investigator: Patrick Verschueren, MD, PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

July 28, 2010

First Submitted That Met QC Criteria

July 29, 2010

First Posted (Estimate)

July 30, 2010

Study Record Updates

Last Update Posted (Actual)

January 22, 2019

Last Update Submitted That Met QC Criteria

January 8, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CareRA
  • 2008-007225-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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