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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004054-41 | EudraCT Number |
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| Name | Class |
|---|---|
| Belgium Health Care Knowledge Centre | OTHER_GOV |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| standard COBRA-Slim induction | Active Comparator | 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.) |
|
| COBRA-Slim Bio-induction | Experimental | 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.) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etanercept 50 MG/ML | Drug | Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Curve (AUC) of Disease Activity Score Based on a 28 Jointcount and C-reactive Protein (DAS28CRP) | Analysis was based on an intention to treat population, which focused on all patients randomized into the study, irrespective if they actually received the randomized treatment. Fifty-five patients were allocated to Standard COBRA-Slim and 55 to COBRA-Slim Bio-induction. This measure is an indication of the total disease-activity over time or long-term effectiveness, a higher area under the curve indicates a higher disease activity over time and so a lower effectiveness over the time frame of the trial. The scale range for the duration of the trial (104 weeks) is 0.0 to 977.6
| baseline, w4, w8, w16, w24, w32, w40, w52, w64, w78, w92 and w104 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Insufficient Responders Achieving Remission (DAS28CRP<2.6) 28 Weeks After Randomization (Short Term Efficacy) to Either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction | Short-time efficacy of disease activity based on a swollen and tender joint count of 28 joints and C-reactive proteine (scale range 0.0 to 9.4; remission: value below 2.6; low disease activity: from 2.6 till 3.2 (included); moderate disease activity: above 3.2 till 5.1; high disease activity: above 5.1). |
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Inclusion Criteria:
Exclusion Criteria:
Previous treatment with:
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-
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Verschueren, MD, PhD | UZ Leuven | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imelda Ziekenhuis Bonheiden | Bonheiden | Antwerpen | 2820 | Belgium | ||
| AZ Herentals |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26399601 | Background | 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. | |
| 19169906 |
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All patients received a COBRA-Slim remission induction regimen, consisting of methotrexate (MTX) with a step-down scheme of glucocorticosteroids (GC).
Patient not reaching low disease activity, based on DAS28CRP, before week 32 or DAS28CRP remission at week 32 were considered early insufficient responders and were eligible for randomization.
Of the 284 patients screened, 276 were eligible for the trial and 122 met the criteria of early insufficient responders to an initial COBRA-Slim remission induction regimen. Of this last group 112 patients were randomized, however 2 were considered randomization errors, 10 patients were eligible for randomization but were not randomized per investigator decision.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard COBRA-Slim Induction | 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.) Leflunomide 10 milligram (MG): Leflunomide 10mg PO daily added to the COBRA-Slim scheme |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 29, 2020 |
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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.
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| Leflunomide 10 milligram (MG) | Drug | Leflunomide 10mg PO daily added to the COBRA-Slim scheme |
|
| From randomization till 28 weeks after randomization. |
| Proportion of Patients in Remission Defined as DAS28CRP<2.6 | Short-time efficacy of disease activity based on a swollen and tender joint count of 28 joints and C-reactive proteine (scale range 0.0 to 9.4; remission: value below 2.6; low disease activity: from 2.6 till 3.2 (included); moderate disease activity: above 3.2 till 5.1; high disease activity: above 5.1). | at week 104 |
| Proportion of Patients Achieving a EULAR Response | proportion of patients achieving a EULAR response, based on actual disease activity on a tender/swollen joint count and C-reactive proteine (DAS28-CRP) 28 weeks after randomization and improvement in DAS28-CRP from baseline. The EULAR response criteria classify patients as good, moderate or non-responders, using the individual amount of change in the DAS28-CRP and the DAS28-CRP value (low, moderate, or high) reached according to the following tabel: DAS28-CRP at endpoint improvement in DAS28-CRP from baseline <=1,2 >0,6 and <= 1,2 <=0,6 <= 3,2 good moderate none >3,2 and <= 5,1 moderate moderate none >5,1 moderate none none Additionally all patients with a good response were also included in the number of participants with at least a moderate response. | at 28 weeks after randomization |
| Proportion of Patients Achieving a EULAR Response | proportion of patients achieving a EULAR response, based on actual disease activity on a tender/swollen joint count and C-reactive proteine (DAS28-CRP) at week 104 and improvement in DAS28-CRP from baseline. The EULAR response criteria classify patients as good, moderate or non-responders, using the individual amount of change in the DAS28-CRP and the DAS28-CRP value (low, moderate, or high) reached according to the following tabel: DAS28-CRP at endpoint improvement in DAS28-CRP from baseline <=1,2 >0,6 and <= 1,2 <=0,6 <= 3,2 good moderate none >3,2 and <= 5,1 moderate moderate none >5,1 moderate none none Additionally all patients with a good response were also included in the number of participants with at least a moderate response. | at week 104 |
| 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. | at 28 weeks after randomization |
| 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. | at week 104 |
| Radiographic Progression | Radiographic progression at week 52 is scored according to the Sharp-Van der Heijde score (SvdH). The SvdH method scores the presence of erosions in 16 joints of hands and wrists (graded from 0 to 5), and in 6 joints of the feet (graded from 0 to 10), and the presence of joint space narrowing in 15 joints of the hands and wrists (graded from 0 to 4) and in 6 joints of the feet (graded from 0 to 4). The maximal range is 280 units for erosion and 168 units for joint space narrowing, summing up to 448 units for the total score. The progression is calculated by subtracting the total score at week 52 minus the total score at baseline (ranging from 0 to 448) Higher values in each (sub) scale represents a worse outcome. | at week 52 |
| Radiographic Progression | Radiographic progression at week 104 is scored according to the Sharp-Van der Heijde score (SvdH). The SvdH method scores the presence of erosions in 16 joints of hands and wrists (graded from 0 to 5), and in 6 joints of the feet (graded from 0 to 10), and the presence of joint space narrowing in 15 joints of the hands and wrists (graded from 0 to 4) and in 6 joints of the feet (graded from 0 to 4). The maximal range is 280 units for erosion and 168 units for joint space narrowing, summing up to 448 units for the total score. The progression is calculated by subtracting the total score at week 104 minus the total score at baseline (ranging from 0 to 448) Higher values in each (sub) scale represents a worse outcome. | at week 104 |
| Herentals |
| Antwerpen |
| 2200 |
| Belgium |
| ZNA Jan Palfijn | Merksem | Antwerpen | 2170 | Belgium |
| GHdC Saint Joseph | Gilly | Henegouwen | 6060 | Belgium |
| Reuma centrum Genk | Genk | Limburg | 3600 | Belgium |
| Reuma Clinic Genk | Genk | Limburg | 3600 | Belgium |
| Reuma Instituut Hasselt | Hasselt | Limburg | 3500 | Belgium |
| CHU UCL Namur ASBL Site Godinne | Yvoir | Namur | 5530 | Belgium |
| OLV Ziekenhuis Aalst | Aalst | Oost Vlaanderen | 9300 | Belgium |
| Regionaal Ziekenhuis Heilig Hart Leuven | Leuven | Vlaams Brabant | 3000 | Belgium |
| UZ Leuven | Leuven | Vlaams Brabant | 3000 | Belgium |
| AZ Jan Portaels | Vilvoorde | Vlaams Brabant | 1800 | Belgium |
| AZ St Lucas Brugge | Bruges | West Vlaanderen | 8310 | Belgium |
| AZ Sint Jan Brugge | Bruges | West-Vlaanderen | 8000 | Belgium |
| CHU Saint Pierre | Brussels | 1000 | Belgium |
| Cliniques Universitaire Saint Luc (UCL) | Brussels | 1000 | Belgium |
| Hôpital Erasme-ULB | Brussels | 1070 | Belgium |
| UZ Brussel | Brussels | 1090 | Belgium |
| CHU Liège | Liège | 4000 | Belgium |
| Background |
| 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. |
| 28968687 | Result | 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. |
| 27432356 | Result | 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. |
| 26058860 | Result | 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. |
| 25889222 | Result | 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. |
| 25483574 | Result | 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. |
| 25359382 | Result | 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. |
| 24559216 | Result | 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. |
| 22751567 | Result | 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. |
| 21454307 | Result | 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. |
| 18050189 | Result | 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. |
| 9251634 | Result | 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. |
| 39117445 | Derived | Bertrand D, Joly J, Neerinckx B, Durez P, Lenaerts J, Joos R, Thevissen K, Zwaenepoel T, Vanhoof J, Di Romana S, Taelman V, Van Essche E, Corluy L, Ribbens C, Vanden Berghe M, Devinck M, Ajeganova S, Durnez A, Boutsen Y, Margaux J, Peene I, Van Offel J, Doumen M, Pazmino S, De Meyst E, Kulyk M, Creten N, Westhovens R, Verschueren P; CareRA2020 Study group. Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial. RMD Open. 2024 Aug 7;10(3):e004535. doi: 10.1136/rmdopen-2024-004535. |
| FG001 | COBRA-Slim Bio-induction | 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.) Etanercept 50 MG/ML: Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Standard COBRA-Slim Induction | 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.) Leflunomide 10 milligram (MG): Leflunomide 10mg PO daily added to the COBRA-Slim scheme |
| BG001 | COBRA-Slim Bio-induction | 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.) Etanercept 50 MG/ML: Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| smoking | Count of Participants | Participants |
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| Rheumatoid factor (RF)/Anti-citrullinated protein antibodies (ACPA ) status | Count of Participants | Participants |
| ||||||||||||||||
| Disease activity (DAS28CRP) | Disease activity score based on a 28 joint count (Tender and Swollen joints) and C-Reactive Proteine (CRP) value. Scale range 0.0 to 9.4. Scale interpretation:
| Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Disease duration | Median | Inter-Quartile Range | days |
|
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Area Under Curve (AUC) of Disease Activity Score Based on a 28 Jointcount and C-reactive Protein (DAS28CRP) | Analysis was based on an intention to treat population, which focused on all patients randomized into the study, irrespective if they actually received the randomized treatment. Fifty-five patients were allocated to Standard COBRA-Slim and 55 to COBRA-Slim Bio-induction. This measure is an indication of the total disease-activity over time or long-term effectiveness, a higher area under the curve indicates a higher disease activity over time and so a lower effectiveness over the time frame of the trial. The scale range for the duration of the trial (104 weeks) is 0.0 to 977.6
| intention to treat (ITT) population | Posted | Mean | 95% Confidence Interval | units on a scale*week | baseline, w4, w8, w16, w24, w32, w40, w52, w64, w78, w92 and w104 |
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| Secondary | Proportion of Insufficient Responders Achieving Remission (DAS28CRP<2.6) 28 Weeks After Randomization (Short Term Efficacy) to Either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction | Short-time efficacy of disease activity based on a swollen and tender joint count of 28 joints and C-reactive proteine (scale range 0.0 to 9.4; remission: value below 2.6; low disease activity: from 2.6 till 3.2 (included); moderate disease activity: above 3.2 till 5.1; high disease activity: above 5.1). | intention to treat (ITT) population | Posted | Number | 95% Confidence Interval | participants | From randomization till 28 weeks after randomization. |
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| Secondary | Proportion of Patients in Remission Defined as DAS28CRP<2.6 | Short-time efficacy of disease activity based on a swollen and tender joint count of 28 joints and C-reactive proteine (scale range 0.0 to 9.4; remission: value below 2.6; low disease activity: from 2.6 till 3.2 (included); moderate disease activity: above 3.2 till 5.1; high disease activity: above 5.1). | intention to treat (ITT) population | Posted | Number | 95% Confidence Interval | participants | at week 104 |
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| Secondary | Proportion of Patients Achieving a EULAR Response | proportion of patients achieving a EULAR response, based on actual disease activity on a tender/swollen joint count and C-reactive proteine (DAS28-CRP) 28 weeks after randomization and improvement in DAS28-CRP from baseline. The EULAR response criteria classify patients as good, moderate or non-responders, using the individual amount of change in the DAS28-CRP and the DAS28-CRP value (low, moderate, or high) reached according to the following tabel: DAS28-CRP at endpoint improvement in DAS28-CRP from baseline <=1,2 >0,6 and <= 1,2 <=0,6 <= 3,2 good moderate none >3,2 and <= 5,1 moderate moderate none >5,1 moderate none none Additionally all patients with a good response were also included in the number of participants with at least a moderate response. | Intention to treat (ITT) population | Posted | Number | 95% Confidence Interval | participants | at 28 weeks after randomization |
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| Secondary | Proportion of Patients Achieving a EULAR Response | proportion of patients achieving a EULAR response, based on actual disease activity on a tender/swollen joint count and C-reactive proteine (DAS28-CRP) at week 104 and improvement in DAS28-CRP from baseline. The EULAR response criteria classify patients as good, moderate or non-responders, using the individual amount of change in the DAS28-CRP and the DAS28-CRP value (low, moderate, or high) reached according to the following tabel: DAS28-CRP at endpoint improvement in DAS28-CRP from baseline <=1,2 >0,6 and <= 1,2 <=0,6 <= 3,2 good moderate none >3,2 and <= 5,1 moderate moderate none >5,1 moderate none none Additionally all patients with a good response were also included in the number of participants with at least a moderate response. | Intention to treat (ITT) population | Posted | Number | 95% Confidence Interval | participants | at week 104 |
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| Secondary | 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. | Intention to treat (ITT) population | Posted | Mean | Standard Deviation | score on a scale | at 28 weeks after randomization |
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| Secondary | 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. | Intention to treat (ITT) population | Posted | Mean | Standard Deviation | score on a scale | at week 104 |
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| Secondary | Radiographic Progression | Radiographic progression at week 52 is scored according to the Sharp-Van der Heijde score (SvdH). The SvdH method scores the presence of erosions in 16 joints of hands and wrists (graded from 0 to 5), and in 6 joints of the feet (graded from 0 to 10), and the presence of joint space narrowing in 15 joints of the hands and wrists (graded from 0 to 4) and in 6 joints of the feet (graded from 0 to 4). The maximal range is 280 units for erosion and 168 units for joint space narrowing, summing up to 448 units for the total score. The progression is calculated by subtracting the total score at week 52 minus the total score at baseline (ranging from 0 to 448) Higher values in each (sub) scale represents a worse outcome. | Intention to treat (ITT) population | Posted | Mean | Standard Deviation | units on a scale | at week 52 |
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| Secondary | Radiographic Progression | Radiographic progression at week 104 is scored according to the Sharp-Van der Heijde score (SvdH). The SvdH method scores the presence of erosions in 16 joints of hands and wrists (graded from 0 to 5), and in 6 joints of the feet (graded from 0 to 10), and the presence of joint space narrowing in 15 joints of the hands and wrists (graded from 0 to 4) and in 6 joints of the feet (graded from 0 to 4). The maximal range is 280 units for erosion and 168 units for joint space narrowing, summing up to 448 units for the total score. The progression is calculated by subtracting the total score at week 104 minus the total score at baseline (ranging from 0 to 448) Higher values in each (sub) scale represents a worse outcome. | Intention to treat (ITT) population. | Posted | Mean | Standard Deviation | units on a scale | at week 104 |
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(Serious) adverse reactions or events of interest are collected over the duration of the trial e.g. 2 years (from screening till w104)
In the CareRA2020 trial, only (serious) events related to rheumatoid arthritis (RA), the RA treatment, or in case of an event of special interest (as specified in the protocol and including deaths) are to be reported according to the protocol. Collection of these reactions was done by delegated study staff questioning the patient at each visit.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard COBRA-Slim Induction | 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.) Leflunomide 10 milligram (MG): Leflunomide 10mg PO daily added to the COBRA-Slim scheme | 1 | 55 | 4 | 55 | 43 | 55 |
| EG001 | COBRA-Slim Bio-induction | 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.) Etanercept 50 MG/ML: Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme | 1 | 55 | 5 | 55 | 47 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| aortic dissection | Vascular disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| myocardial ischaemia | Cardiac disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| stress cardiomyopathy | Cardiac disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| cerobrovascular accident | Nervous system disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| leukopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| psychiatric decompensation | Psychiatric disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| bursitis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| enterococcal sepsis | Infections and infestations | MedDRA (25.1) | Non-systematic Assessment |
| |
| respiratory tract infection | Infections and infestations | MedDRA (25.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| fatigue | General disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| injection site erythema | General disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| pyrexia | General disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| palpitations | Cardiac disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| headache | Nervous system disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| nausea | Gastrointestinal disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| abdominal discomfort | Gastrointestinal disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| diarrhoea | Gastrointestinal disorders | MedDRA (25.1) | Non-systematic Assessment |
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| abdominal pain upper | Gastrointestinal disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (25.1) | Non-systematic Assessment |
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| dyspepsia | Gastrointestinal disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| hepatic function abnormal | Hepatobiliary disorders | MedDRA (25.1) | Non-systematic Assessment |
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| alopecia | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| acne | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Non-systematic Assessment |
| |
| nasopharyngitis | Infections and infestations | MedDRA (25.1) | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (25.1) | Non-systematic Assessment |
| |
| bronchitis | Infections and infestations | MedDRA (25.1) | Non-systematic Assessment |
|
Institution/PI may only publish the Results provided that Sponsor has duly published the main Study publication. Once the main Study publication has been duly published by the Sponsor, Institution/PI are entitled to publish the Results provided that Sponsor has granted its prior written approval with Institution's/PI's proposed publication. If SPONSOR did not respond within 90 days, the institution/PI may proceed with the publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Dr. Patrick Verschueren | UZLeuven | +3216342541 | patrick.verschueren@uzleuven.be |
| Aug 3, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068800 | Etanercept |
| ID | Term |
|---|---|
| D007141 | Immunoglobulin Fc Fragments |
| D007128 | Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D007127 | Immunoglobulin Constant Regions |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D018124 | Receptors, Tumor Necrosis Factor |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
Not provided
Not provided
| Between 18 and 65 years |
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| >=65 years |
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