Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis. - Full Text View

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:

MedlinePlus related topics: Rheumatoid Arthritis

U.S. FDA Resources

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 2014 (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

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

Contacts

Contact: Patrick Verschueren, MD, PhD	+32 16 34 25 41	reumatologie-admin@uz.kuleuven.ac.be
Contact: René Westhovens, MD, PhD	+32 16 34 25 41	reumatologie-admin@uz.kuleuven.ac.be

Locations

Belgium
OLV Ziekenhuis	Recruiting
Aalst, Belgium, 9300
Contact: Isabelle Ravelingien, MD
Principal Investigator: Isabelle Ravelingien, MD
ASZ	Not yet recruiting
Aalst, Belgium, 9300
Contact: Godelieve Gyselbrecht, MD
Principal Investigator: Godelieve Gyselbrecht, MD
Sub-Investigator: Marthe Vandenberghe, MD
Imelda Ziekenhuis	Recruiting
Bonheiden, Belgium, 2820
Contact: Els Van Essche, MD
Principal Investigator: Els Van Essche, MD
Sub-Investigator: Kathleen Declerck, MD
AZ St Lucas	Not yet recruiting
Brugge, Belgium, 8310
Contact: Griet De Brabanter, MD
Sub-Investigator: Bea Mayeart, MD
Principal Investigator: Griet De Brabanter, MD
Reumacentrum	Not yet recruiting
Genk, Belgium, 3600
Contact: Jan Remans, MD, PhD
Principal Investigator: Jan Remans, MD, PhD
Sub-Investigator: Philip Remans, MD, PhD
Reuma praktijk	Recruiting
Genk, Belgium, 3600
Contact: Piet Geusens, MD, PhD
Principal Investigator: Piet Geusens, MD, PhD
Sub-Investigator: Johan Vanhoof, MD
Sub-Investigator: Hubert Berghs, MD
Sub-Investigator: Marleen Coppens, MD
Sub-Investigator: Inge Vantilt, MD
UZ Gent, dept. of Rheumatology	Not yet recruiting
Gent, Belgium, 9000
Contact: Filip Van den Bosch, MD, PhD +32 9 332 28 63 filip.vandenbosch@ugent.be
Principal Investigator: Filip Van den Bosch, MD, PhD
Reumapraktijk	Not yet recruiting
Hasselt, Belgium, 3500
Contact: Pascale Volders, MD
Principal Investigator: Pascale Volders, MD
Sub-Investigator: Anne Sileghem, MD
Reuma instituut Hasselt	Recruiting
Hasselt, Belgium, 3500
Contact: Paul Van Wanghe, MD
Principal Investigator: Paul Van Wanghe, MD
Sub-Investigator: Jan Lenaerts, MD
Sub-Investigator: Luc Corluy, MD
Sub-Investigator: Christine Langenaken, MD
Jan Yperman Ziekenhuis	Not yet recruiting
Ieper, Belgium, 8900
Contact: Filip Lensen, MD
Principal Investigator: Filip Lensen, MD
AZ groeninge	Recruiting
Kortrijk, Belgium, 8500
Contact: Klaas Vandevyvere, MD
Principal Investigator: Klaas Vandevyvere, MD
Sub-Investigator: Anne Durnez, MD, PhD
HHart Ziekenhuis	Recruiting
Leuven, Belgium, 3000
Contact: Veerle Taelman, MD
Principal Investigator: Veerle Taelman, MD
Universitaire Ziekenhuizen Leuven	Recruiting
Leuven, Belgium, 3000
Contact: Patrick Verschueren, MD, PhD
Principal Investigator: Patrick Verschueren, MD, PhD
Sub-Investigator: René Westhovens, MD, PhD
MCH	Not yet recruiting
Leuven, Belgium, 3000
Contact: Kilian Verschueren, MD
Principal Investigator: Kilian Verschueren, MD
AZ St maarten	Not yet recruiting
Mechelen, Belgium, 2800
Contact: Kilian Verschueren, MD
Principal Investigator: Kilian Verschueren, MD
ZNA Jan Palfijn	Recruiting
Merksem, Belgium, 2170
Contact: Frank Raeman, MD
Principal Investigator: Frank Raeman, MD
Sub-Investigator: Rik Joos, MD
Sub-Investigator: Ann Verbruggen, MD
Henri Serruys ziekenhuis	Not yet recruiting
Oostende, Belgium, 8400
Contact: Filip Lensen, MD
Principal Investigator: Filip Lensen, MD

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:

Verschueren P, Esselens G, Westhovens R. Predictors of remission, normalized physical function, and changes in the working situation during follow-up of patients with early rheumatoid arthritis: an observational study. Scand J Rheumatol. 2009 May-Jun;38(3):166-72.

Verschueren P, Esselens G, Westhovens R. Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis. Rheumatology (Oxford). 2008 Jan;47(1):59-64. Epub 2007 Nov 26.

Durez P, Malghem J, Nzeusseu Toukap A, Depresseux G, Lauwerys BR, Westhovens R, Luyten FP, Corluy L, Houssiau FA, Verschueren P. Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Arthritis Rheum. 2007 Dec;56(12):3919-27.

Esselens G, Westhovens R, Verschueren P. Effectiveness of an integrated outpatient care programme compared with present-day standard care in early rheumatoid arthritis. Musculoskeletal Care. 2009 Mar;7(1):1-16.

Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde DM, Boonen A, van der Linden S. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309-18. Erratum in: Lancet 1998 Jan 17;351(9097):220.

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:	October 4, 2011
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 May 22, 2013