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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172639
• Other study ID #: CareRA
• Secondary ID: 2008-007225-39
• Status: Completed
• Phase: Phase 4
• Start date: February 2009
• Est. completion date: June 2015

Study information

• Verified date: January 2019
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Methotrexate tablet
• Sulfasalazine
Sulfasalazine tablet
• Leflunomide
Leflunomide tablet
• Prednisone
Prednisone tablet

Locations

Country	Name	City	State
Belgium	ASZ	Aalst
Belgium	OLV Ziekenhuis	Aalst
Belgium	Imelda Ziekenhuis	Bonheiden
Belgium	AZ St Lucas	Brugge
Belgium	Reuma praktijk	Genk
Belgium	Reumacentrum	Genk
Belgium	UZ Gent, dept. of Rheumatology	Gent
Belgium	Reuma instituut Hasselt	Hasselt
Belgium	Reumapraktijk	Hasselt
Belgium	Jan Yperman Ziekenhuis	Ieper
Belgium	AZ groeninge	Kortrijk
Belgium	HHart Ziekenhuis	Leuven
Belgium	MCH	Leuven
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Belgium	AZ St maarten	Mechelen
Belgium	ZNA Jan Palfijn	Merksem
Belgium	Henri Serruys ziekenhuis	Oostende

Sponsors (2)

Lead Sponsor	Collaborator
P. Verschueren	Agentschap voor Innovatie door Wetenschap en Technologie

Country where clinical trial is conducted

Belgium, 

References & Publications (9)

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. — View Citation

De Cock D, Van der Elst K, Meyfroidt S, Verschueren P, Westhovens R. The optimal combination therapy for the treatment of early rheumatoid arthritis. Expert Opin Pharmacother. 2015;16(11):1615-25. doi: 10.1517/14656566.2015.1056735. Epub 2015 Jun 10. Review. — View Citation

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. — View Citation

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. doi: 10.1002/msc.136. — View Citation

Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, Raeman F, Ravelingien I, Vandevyvere K, Lenaerts J, Geens E, Geusens P, Vanhoof J, Durnez A, Remans J, Vander Cruyssen B, Van Essche E, Sileghem A, De Brabanter G, Joly J, Meyfroidt S, V — View Citation

Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, Raeman F, Ravelingien I, Vandevyvere K, Lenaerts J, Geens E, Geusens P, Vanhoof J, Durnez A, Remans J, Vander Cruyssen B, Van Essche E, Sileghem A, De Brabanter G, Joly J, Meyfroidt S, V — View Citation

Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, Raeman F, Ravelingien I, Vandevyvere K, Lenaerts J, Geens E, Geusens P, Vanhoof J, Durnez A, Remans J, Vander Cruyssen B, Van Essche E, Sileghem A, De Brabanter G, Joly J, Van der Elst K — View Citation

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. — View Citation

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. doi: 10.1080/03009740802484846. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Remission According to DAS28-CRP at 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
Primary	Remission According to DAS28-CRP at 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
Primary	Remission According to DAS28-CRP at 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	Remission According to SDAI (Simple Disease Activity Index) at 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
Secondary	Remission According to SDAI at 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
Secondary	Remission According to SDAI at 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
Secondary	Clinically Significant Change in HAQ Score	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