Back to resultsCOBRA-Slim With or Without Fast Access to TNF Blockade for Remission Induction in Early RA (CareRA2020)
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Etanercept 50 MG/ML
Leflunomide 10 milligram (MG)
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring COBRA-Slim, Accelerated access to anti-TNF, treat to target, remission induction
Eligibility Criteria
Inclusion Criteria:
- Age 18 years and older
- Diagnosis of RA as defined by the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for early RA
- Early RA defined by a diagnosis made ≤ 1 year ago.
- Use a reliable method of contraception for women of childbearing potential to be evaluated as in daily clinical practice
- Able and willing to give written informed consent and to participate in the study
- Understanding and able to write Dutch or French
Exclusion Criteria:
Previous treatment with:
- Methotrexate (MTX) or leflunomide
- cyclophosphamide, azathioprine or cyclosporine
- sulphasalazine (SSZ) for more than 3 weeks
- hydroxychloroquine for more than 6 weeks
- oral Glucocorticoids (GC) for more than 4 weeks within 4 months before screening
- oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline
- oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline
- intra-articular GC within 4 weeks before BL
- an investigational drug for the treatment/prevention of RA
- History of chronic heart failure
- History of severe infections or chronic infection
- History of malignant neoplasm within 5 years
- Contra indications for GC
- Contra indications for TNF blocking agents
- Contra indications for MTX or leflunomide
- 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 for woman of childbearing potential (as in daily clinical practice)
- Alcohol or drug abuse
- Active tuberculosis (TB)
- Latent TB unless adequate prophylactic treatment is given according to local guidelines
- No access to the Belgian Health Insurance system-
Sites / Locations
- Imelda Ziekenhuis Bonheiden
- AZ Herentals
- ZNA Jan Palfijn
- GHdC Saint Joseph
- Reuma centrum Genk
- Reuma Clinic Genk
- Reuma Instituut Hasselt
- CHU UCL Namur ASBL Site Godinne
- OLV Ziekenhuis Aalst
- Regionaal Ziekenhuis Heilig Hart Leuven
- UZ Leuven
- AZ Jan Portaels
- AZ St Lucas Brugge
- AZ Sint Jan Brugge
- UZ Brussel
- CHU Saint Pierre
- Cliniques Universitaire Saint Luc (UCL)
- Hôpital Erasme-ULB
- CHU Liège
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
standard COBRA-Slim induction
COBRA-Slim Bio-induction
Arm Description
Leflunomide 10mg PO daily added to the COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)
Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)
Outcomes
Primary Outcome Measures
Area Under Curve (AUC) DAS28 C reactive protein (CRP)
Secondary Outcome Measures
Remission
DAS28 CRP<2.6
Remission
DAS28 CRP<2.6
EULAR response
EULAR response
Health Assessment Questionnaire (HAQ) response
HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.
Health Assessment Questionnaire (HAQ) response
HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.
Radiographic progression
Radiographic progression
Analysis of reported (Serious) Adverse Reactions
(Serious) Adverse Reactions will be captured by the investigator using his/her clinical judgement. Number of events will be analysed and described in total and per patient
Full Information
NCT ID
NCT03649061
First Posted
July 30, 2018
Last Updated
July 4, 2022
Sponsor
P. Verschueren
Collaborators
Belgium Health Care Knowledge Centre
1. Study Identification
Unique Protocol Identification Number
NCT03649061
Brief Title
COBRA-Slim With or Without Fast Access to TNF Blockade for Remission Induction in Early RA
Acronym
CareRA2020
Official Title
Effectiveness of a Combination of Methotrexate and a Step Down Glucocorticoid Regimen (COBRA-Slim) for Remission Induction in Patients With Early Rheumatoid Arthritis (RA), With or Without Fast Access to 24 Weeks of Tumor Necrosis Factor (TNF) Blockade in Insufficient Responders, a Randomized, Multicenter, Pragmatic Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
June 8, 2018 (Actual)
Primary Completion Date
July 1, 2022 (Actual)
Study Completion Date
July 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
P. Verschueren
Collaborators
Belgium Health Care Knowledge Centre
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In the Care in Rheumatoid Arthritis (CareRA) trial (NCT01172639) about 70% of early RA patients are in remission at the 2 year evaluation point independent of the combination scheme used.
Interesting to see is that the 30% of insufficient responders can be identified in an early stage of the treatment course.
The purpose of the present study is to investigate if, for patients with an insufficient response to a COBRA-Slim regimen, accelerated access to a short course of anti-TNF therapy already early after treatment initiation (from w8 until w32) could improve outcomes compared to a more traditional treat to target sequence.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
COBRA-Slim, Accelerated access to anti-TNF, treat to target, remission induction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Insufficient responders to a COBRA-Slim strategy, defined as not reaching low disease activity based on DAS28 CRP from week 8 until week 32 or not reaching remission based on DAS28 CRP at week 32, will be randomly assigned to one of the two arms.
Randomization will be balanced according to time-point of randomization, baseline (BL) disease activity and Anti-Citrullinated Protein Antibody (ACPA) and Rheumatoid Factor (RF) status to ensure comparability of the treatment groups with respect to these prognostic variables.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
284 (Actual)
8. Arms, Groups, and Interventions
Arm Title
standard COBRA-Slim induction
Arm Type
Active Comparator
Arm Description
Leflunomide 10mg PO daily added to the COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)
Arm Title
COBRA-Slim Bio-induction
Arm Type
Experimental
Arm Description
Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)
Intervention Type
Drug
Intervention Name(s)
Etanercept 50 MG/ML
Intervention Description
Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme
Intervention Type
Drug
Intervention Name(s)
Leflunomide 10 milligram (MG)
Intervention Description
Leflunomide 10mg PO daily added to the COBRA-Slim scheme
Primary Outcome Measure Information:
Title
Area Under Curve (AUC) DAS28 C reactive protein (CRP)
Time Frame
over 104 weeks
Secondary Outcome Measure Information:
Title
Remission
Description
DAS28 CRP<2.6
Time Frame
at 28 weeks after randomization
Title
Remission
Description
DAS28 CRP<2.6
Time Frame
at week 104
Title
EULAR response
Time Frame
at 28 weeks after randomization
Title
EULAR response
Time Frame
at week 104
Title
Health Assessment Questionnaire (HAQ) response
Description
HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.
Time Frame
at 28 weeks after randomization
Title
Health Assessment Questionnaire (HAQ) response
Description
HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.
Time Frame
at week 104
Title
Radiographic progression
Time Frame
at week 52
Title
Radiographic progression
Time Frame
at week 104
Title
Analysis of reported (Serious) Adverse Reactions
Description
(Serious) Adverse Reactions will be captured by the investigator using his/her clinical judgement. Number of events will be analysed and described in total and per patient
Time Frame
over 104 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years and older
Diagnosis of RA as defined by the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for early RA
Early RA defined by a diagnosis made ≤ 1 year ago.
Use a reliable method of contraception for women of childbearing potential to be evaluated as in daily clinical practice
Able and willing to give written informed consent and to participate in the study
Understanding and able to write Dutch or French
Exclusion Criteria:
Previous treatment with:
Methotrexate (MTX) or leflunomide
cyclophosphamide, azathioprine or cyclosporine
sulphasalazine (SSZ) for more than 3 weeks
hydroxychloroquine for more than 6 weeks
oral Glucocorticoids (GC) for more than 4 weeks within 4 months before screening
oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline
oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline
intra-articular GC within 4 weeks before BL
an investigational drug for the treatment/prevention of RA
History of chronic heart failure
History of severe infections or chronic infection
History of malignant neoplasm within 5 years
Contra indications for GC
Contra indications for TNF blocking agents
Contra indications for MTX or leflunomide
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 for woman of childbearing potential (as in daily clinical practice)
Alcohol or drug abuse
Active tuberculosis (TB)
Latent TB unless adequate prophylactic treatment is given according to local guidelines
No access to the Belgian Health Insurance system-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Verschueren, MD, PhD
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
Imelda Ziekenhuis Bonheiden
City
Bonheiden
State/Province
Antwerpen
ZIP/Postal Code
2820
Country
Belgium
Facility Name
AZ Herentals
City
Herentals
State/Province
Antwerpen
ZIP/Postal Code
2200
Country
Belgium
Facility Name
ZNA Jan Palfijn
City
Merksem
State/Province
Antwerpen
ZIP/Postal Code
2170
Country
Belgium
Facility Name
GHdC Saint Joseph
City
Gilly
State/Province
Henegouwen
ZIP/Postal Code
6060
Country
Belgium
Facility Name
Reuma centrum Genk
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Reuma Clinic Genk
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Reuma Instituut Hasselt
City
Hasselt
State/Province
Limburg
ZIP/Postal Code
3500
Country
Belgium
Facility Name
CHU UCL Namur ASBL Site Godinne
City
Yvoir
State/Province
Namur
ZIP/Postal Code
5530
Country
Belgium
Facility Name
OLV Ziekenhuis Aalst
City
Aalst
State/Province
Oost Vlaanderen
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Regionaal Ziekenhuis Heilig Hart Leuven
City
Leuven
State/Province
Vlaams Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
State/Province
Vlaams Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Name
AZ Jan Portaels
City
Vilvoorde
State/Province
Vlaams Brabant
ZIP/Postal Code
1800
Country
Belgium
Facility Name
AZ St Lucas Brugge
City
Brugge
State/Province
West Vlaanderen
ZIP/Postal Code
8310
Country
Belgium
Facility Name
AZ Sint Jan Brugge
City
Brugge
State/Province
West-Vlaanderen
ZIP/Postal Code
8000
Country
Belgium
Facility Name
UZ Brussel
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
CHU Saint Pierre
City
Brussel
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Cliniques Universitaire Saint Luc (UCL)
City
Brussel
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Hôpital Erasme-ULB
City
Brussel
ZIP/Postal Code
1070
Country
Belgium
Facility Name
CHU Liège
City
Liège
ZIP/Postal Code
4000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
26399601
Citation
Van der Elst K, De Cock D, Vecoven E, Arat S, Meyfroidt S, Joly J, Moons P, Verschueren P, Westhovens R, CareRA Study Group. Are illness perception and coping style associated with the delay between symptom onset and the first general practitioner consultation in early rheumatoid arthritis management? An exploratory study within the CareRA trial. Scand J Rheumatol. 2016;45(3):171-8. doi: 10.3109/03009742.2015.1074278. Epub 2015 Sep 23.
Results Reference
background
PubMed Identifier
19169906
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.
Results Reference
background
PubMed Identifier
28968687
Citation
Verschueren P, Westhovens R. The use of glucocorticoids in early rheumatoid arthritis. Rheumatology (Oxford). 2018 Aug 1;57(8):1316-1317. doi: 10.1093/rheumatology/kex271. No abstract available.
Results Reference
result
PubMed Identifier
27432356
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, 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.
Results Reference
result
PubMed Identifier
26058860
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.
Results Reference
result
PubMed Identifier
25889222
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, 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.
Results Reference
result
PubMed Identifier
25483574
Citation
Meyfroidt S, Van der Elst K, De Cock D, Joly J, Westhovens R, Hulscher M, Verschueren P. Patient experiences with intensive combination-treatment strategies with glucocorticoids for early rheumatoid arthritis. Patient Educ Couns. 2015 Mar;98(3):384-90. doi: 10.1016/j.pec.2014.11.011. Epub 2014 Nov 20.
Results Reference
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PubMed Identifier
25359382
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, 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.
Results Reference
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PubMed Identifier
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Citation
Meyfroidt S, van Hulst L, De Cock D, Van der Elst K, Joly J, Westhovens R, Hulscher M, Verschueren P. Factors influencing the prescription of intensive combination treatment strategies for early rheumatoid arthritis. Scand J Rheumatol. 2014;43(4):265-72. doi: 10.3109/03009742.2013.863382. Epub 2014 Feb 24.
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PubMed Identifier
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Citation
Westhovens R, Verschueren P. Rheumatoid arthritis: defining remission in patients with RA in clinical practice. Nat Rev Rheumatol. 2012 Aug;8(8):445-7. doi: 10.1038/nrrheum.2012.111. Epub 2012 Jul 3. No abstract available.
Results Reference
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PubMed Identifier
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Citation
Verschueren P, Westhovens R. Optimal care for early RA patients: the challenge of translating scientific data into clinical practice. Rheumatology (Oxford). 2011 Jul;50(7):1194-200. doi: 10.1093/rheumatology/ker131. Epub 2011 Mar 30.
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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. doi: 10.1002/art.23055.
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Citation
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. Erratum In: Lancet 1998 Jan 17;351(9097):220.
Results Reference
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COBRA-Slim With or Without Fast Access to TNF Blockade for Remission Induction in Early RA
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