Effectiveness in Daily Practice of Different Treatment St... | NCT01172639 | Trialant
NCT01172639
Sponsor
P. Verschueren
Status
Completed
Last Update Posted
Jan 22, 2019Actual
Enrollment
400Actual
Phase
Phase 4
Conditions
Rheumatoid Arthritis
Interventions
Methotrexate
Sulfasalazine
Leflunomide
Prednisone
Countries
Belgium
Protocol Section
Identification Module
NCT ID
NCT01172639
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CareRA
Secondary IDs
ID
Type
Description
Link
2008-007225-39
EudraCT Number
Brief Title
Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.
Official Title
A 2 Year Prospective Multicentre Randomised Controlled Trial Comparing Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.
Acronym
Not provided
Organization
Universitaire Ziekenhuizen KU LeuvenOTHER
Status Module
Record Verification Date
Jan 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 2009
Primary Completion Date
Jun 2015Actual
Completion Date
Jun 2015Actual
First Submitted Date
Jul 28, 2010
First Submission Date that Met QC Criteria
Jul 29, 2010
First Posted Date
Jul 30, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
May 16, 2018
Results First Submitted that Met QC Criteria
May 16, 2018
Results First Posted Date
Dec 10, 2018Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 8, 2019
Last Update Posted Date
Jan 22, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
P. Verschueren, Prof. Dr., Universitaire Ziekenhuizen KU LeuvenSponsor-Investigator
Lead Sponsor
P. VerschuerenOTHER
Collaborators
Name
Class
Agentschap voor Innovatie door Wetenschap en Technologie
OTHER
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief 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.
Detailed Description
Not provided
Conditions Module
Conditions
Rheumatoid Arthritis
Keywords
CoBRA
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 4
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
400Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
CoBRA classic high risk group
Other
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
Drug: Sulfasalazine
Drug: Prednisone
CoBRA slim high risk group
Other
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
Drug: Prednisone
CoBRA avant-garde high risk group
Other
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
Drug: Leflunomide
Drug: Prednisone
CoBRA slim low risk group
Other
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
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Methotrexate
Drug
Methotrexate tablet
CoBRA avant-garde high risk group
CoBRA classic high risk group
CoBRA slim high risk group
CoBRA slim low risk group
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
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
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 Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
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.
There were 379 patients randomised to a treatment arm, 21 patients not randomised: 1 screen failure, 10 withdrawals by subject, 10 randomisation errors
Recruitment Details
We recruited 400 participants between January 2009 and May 2013. There were 13 participating Flemish rheumatology centers (2 academic centers, 7 general hospitals and 4 private practices).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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
FG001
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Before randomisation patients were stratified to a high-risk or low-risk group according to the presence of risk factors at screening (having erosions, rheumatoid factor and/or anticitrullinated protein antibody and a high disease activity score calculated with C-reactive protein (DAS28-CRP)). Randomisation to treatment arms was performed via a digitally generated sequence. Patients in the high-risk group were randomised into CoBRA Classic, Clim or Avant-Garde arm. Patients in the low-risk group were randomised into CoBRA Slim or Tight Step Up arm.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Methotrexate
Drug: Prednisone
Tight Step Up low risk group
Other
Methotrexate 15mg tablet by mouth, weekly for entire trial
No oral steroids allowed during the first year of the trial
Drug: Methotrexate
Tight Step Up low risk group
Ledertrexate
Sulfasalazine
Drug
Sulfasalazine tablet
CoBRA classic high risk group
Salazopyrine
Leflunomide
Drug
Leflunomide tablet
CoBRA avant-garde high risk group
Arava
Prednisone
Drug
Prednisone tablet
CoBRA avant-garde high risk group
CoBRA classic high risk group
CoBRA slim high risk group
CoBRA slim low risk group
week 16
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
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
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
Aalst
9300
Belgium
Imelda Ziekenhuis
Bonheiden
2820
Belgium
AZ St Lucas
Bruges
8310
Belgium
Reuma praktijk
Genk
3600
Belgium
Reumacentrum
Genk
3600
Belgium
UZ Gent, dept. of Rheumatology
Ghent
9000
Belgium
Reuma instituut Hasselt
Hasselt
3500
Belgium
Reumapraktijk
Hasselt
3500
Belgium
Jan Yperman Ziekenhuis
Ieper
8900
Belgium
AZ groeninge
Kortrijk
8500
Belgium
HHart Ziekenhuis
Leuven
3000
Belgium
MCH
Leuven
3000
Belgium
Universitaire Ziekenhuizen Leuven
Leuven
3000
Belgium
AZ St maarten
Mechelen
2800
Belgium
ZNA Jan Palfijn
Merksem
2170
Belgium
Henri Serruys ziekenhuis
Ostend
8400
Belgium
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. doi: 10.1093/rheumatology/kem288. 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. doi: 10.1002/art.23055.
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.
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. doi: 10.1016/S0140-6736(97)01300-7.
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.
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, Van der Elst K, Westhovens R. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015 Jan;74(1):27-34. doi: 10.1136/annrheumdis-2014-205489. Epub 2014 Oct 30.
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, Meyfroidt S, Westhovens R; CareRA study group. Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial. Arthritis Res Ther. 2015 Apr 9;17(1):97. doi: 10.1186/s13075-015-0611-8.
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, Van der Elst K, Westhovens R. Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial. Ann Rheum Dis. 2017 Mar;76(3):511-520. doi: 10.1136/annrheumdis-2016-209212. Epub 2016 Jul 18.
Pazmino S, Boonen A, De Cock D, Stouten V, Joly J, Bertrand D, Westhovens R, Verschueren P. Short-term glucocorticoids reduce risk of chronic NSAID and analgesic use in early methotrexate-treated rheumatoid arthritis patients with favourable prognosis: subanalysis of the CareRA randomised controlled trial. RMD Open. 2021 May;7(2):e001615. doi: 10.1136/rmdopen-2021-001615.
Stouten V, Westhovens R, De Cock D, Van der Elst K, Pazmino S, Bertrand D, Joly J, Verschueren P. Having a co-morbidity predicts worse outcome in early rheumatoid arthritis despite intensive treatment: a post hoc evaluation of the pragmatic randomized controlled CareRA trial. Rheumatology (Oxford). 2021 Aug 2;60(8):3699-3708. doi: 10.1093/rheumatology/keaa841.
Pazmino S, Lovik A, Boonen A, De Cock D, Stouten V, Joly J, Bertrand D, Van der Elst K, Westhovens R, Verschueren P. Does Including Pain, Fatigue, and Physical Function When Assessing Patients with Early Rheumatoid Arthritis Provide a Comprehensive Picture of Disease Burden? J Rheumatol. 2021 Feb;48(2):174-178. doi: 10.3899/jrheum.200758. Epub 2020 Nov 15.
Pazmino S, Boonen A, Stouten V, De Cock D, Joly J, Van der Elst K, Westhovens R, Verschueren P. Two-year cost-effectiveness of different COBRA-like intensive remission induction schemes in early rheumatoid arthritis: a piggyback study on the pragmatic randomised controlled CareRA trial. Ann Rheum Dis. 2020 May;79(5):556-565. doi: 10.1136/annrheumdis-2019-216874. Epub 2020 Apr 2.
Stouten V, Michiels S, Westhovens R, De Cock D, Belba A, Pazmino S, Van der Elst K, Joly J, Verschueren P. Effectiveness of maintenance therapy with methotrexate compared with leflunomide for patients with RA having achieved disease control with both these drugs: results of a predefined sub-analysis of CareRA, a pragmatic RCT. Clin Rheumatol. 2020 Sep;39(9):2593-2601. doi: 10.1007/s10067-020-05008-4. Epub 2020 Mar 12.
Stouten V, Westhovens R, Pazmino S, De Cock D, Van der Elst K, Joly J, Verschueren P; CareRA study group. Effectiveness of different combinations of DMARDs and glucocorticoid bridging in early rheumatoid arthritis: two-year results of CareRA. Rheumatology (Oxford). 2019 Dec 1;58(12):2284-2294. doi: 10.1093/rheumatology/kez213.
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
FG002
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
FG003
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
FG004
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
FG00098 subjects
FG00198 subjects
FG00293 subjects
FG00343 subjects
FG00447 subjects
Week 16
FG00094 subjects
FG00196 subjects
FG00291 subjects
FG00339 subjects
FG00447 subjects
Week 52
FG00089 subjects
FG00189 subjects
FG00288 subjects
FG00338 subjects
FG00445 subjects
COMPLETED
FG00085 subjects
FG00187 subjects
FG00277 subjects
FG00332 subjects
FG00441 subjects
NOT COMPLETED
FG00013 subjects
FG00111 subjects
FG00216 subjects
FG00311 subjects
FG0046 subjects
Type
Comment
Reasons
Death
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Lost to Follow-up
FG0009 subjects
FG0017 subjects
FG00211 subjects
FG0036 subjects
FG004
Withdrawal by Subject
FG0003 subjects
FG0013 subjects
FG0025 subjects
FG0035 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
BG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
BG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
BG003
CoBRA Slim Low Risk Group
MTX
Step down steroid half dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
BG004
Tight Step Up Low Risk Group
MTX
No additional oral steroids allowed
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00098
BG00198
BG00293
BG00343
BG00447
BG005379
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00053.2± 11.9
BG00151.8± 13.1
BG00251.1± 12.8
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00064
BG00163
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Caucasian
Title
Measurements
BG00095
BG00196
BG002
Smoking status
Count of Participants
Participants
Title
Denominators
Categories
current
Title
Measurements
BG00030
BG00130
BG002
Symptom duration
Mean
Standard Deviation
weeks
Title
Denominators
Categories
Title
Measurements
BG00033.8± 35.5
BG00133.2± 38.2
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
ITT = intention to treat analysis (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
week 16
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
OG003
CoBRA Slim Low Risk Group
MTX
Step down steroid half dose
OG004
Tight Step Up Low Risk Group
MTX
No additional oral steroids allowed
Units
Counts
Participants
OG00098
OG00198
OG00293
OG003
Title
Denominators
Categories
Title
Measurements
OG00069
OG00172
OG00261
OG003
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.
ITT (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
week 52
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
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.
ITT (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
week 104
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
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.
ITT (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
week 16
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
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.
ITT (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
week 52
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
OG003
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.
ITT = intention to treat analysis (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
week 104
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
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.
ITT = intention to treat analysis (all randomized subjects included), missing data imputed with Expectation Maximization on complete w104 database.
Posted
Count of Participants
Participants
Baseline-week104
ID
Title
Description
OG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
OG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
OG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
OG003
CoBRA Slim Low Risk Group
MTX
Step down steroid half dose
Time Frame
Adverse event data were collected over a two year period per patient
Description
All adverse events were registered by healthcare professionals questioning the patients at each visit
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
CoBRA Classic High Risk Group
Methotrexate (MTX)
Sulphasalazine
Step down steroid full dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
1
98
21
98
85
98
EG001
CoBRA Slim High Risk Group
MTX
Step down steroid half dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
1
98
22
98
88
98
EG002
CoBRA Avant-garde High Risk Group
MTX
Leflunomide
Step down steroid half dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
0
93
16
93
84
93
EG003
CoBRA Slim Low Risk Group
MTX
Step down steroid half dose
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
0
43
9
43
34
43
EG004
Tight Step Up Low Risk Group
MTX
No additional oral steroids allowed
randomisation: Stratification according to risk factors into two groups. Random assignment to different treatment strategies within strata.
0
47
7
47
45
47
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG0031 events1 affected43 at risk
EG0040 events0 affected47 at risk
Bone marrow supression
Blood and lymphatic system disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Angina
Cardiac disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Atrial fibrillation
Cardiac disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0014 events3 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Atrioventricular block third degree
Cardiac disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Myocardial infarction
Cardiac disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0012 events2 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Pericarditis
Cardiac disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0012 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Sinus venosus defect
Cardiac disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Uncontrolled diabetes mellitus
Endocrine disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0022 events2 affected93 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Gastroenteritis
Gastrointestinal disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0011 events1 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Reflux oesophagitis
Gastrointestinal disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Volvulus
Gastrointestinal disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Anaphylaxis after a wasp sting
Immune system disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Bacterial infection
Infections and infestations
Systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Viral infection
Infections and infestations
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Cholecystitis
Hepatobiliary disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Post procedural complication
Injury, poisoning and procedural complications
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Trauma
Injury, poisoning and procedural complications
Systematic Assessment
EG0001 events1 affected98 at risk
EG0012 events2 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Hernia diaphragmatica
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Intervertebral disc disorder
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0002 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0024 events3 affected93 at risk
EG003
Ischialgy leg
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Lumbago
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Rheumatoid arthritis flare
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0011 events1 affected98 at risk
EG0022 events2 affected93 at risk
EG003
Septic bursitis olecrani
Infections and infestations
Systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Baker's cyst
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Breast cancer malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0003 events3 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Cervixcarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Cholesteatoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Endometrioid adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Intestinal polyps
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Kidney cancer malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Lung cancer malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Lung noduli
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected98 at risk
EG0020 events0 affected93 at risk
EG003
Neoplasms parotid gland
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected98 at risk
EG0021 events1 affected93 at risk
EG003
Noduli submandibular salivary glands
Neoplasms benign, malignant and unspecified (incl cysts and polyps)