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COBRA-Slim With or Without Fast Access to TNF Blockade for Remission Induction in Early RA (CareRA2020)

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ClinicalTrials.gov Identifier: NCT03649061
Recruitment Status : Active, not recruiting
First Posted : August 28, 2018
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
Belgium Health Care Knowledge Centre
Information provided by (Responsible Party):
P. Verschueren, Universitaire Ziekenhuizen Leuven

Study Description
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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.


Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Etanercept 50 MG/ML Drug: Leflunomide 10 milligram (MG) Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 284 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : June 8, 2018
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 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.)
 Drug: Leflunomide 10 milligram (MG)
Leflunomide 10mg PO daily added to the COBRA-Slim scheme
Experimental: 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.)
 Drug: Etanercept 50 MG/ML
Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme


Outcome Measures
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Primary Outcome Measures :
  1. Area Under Curve (AUC) DAS28 C reactive protein (CRP) [ Time Frame: over 104 weeks ]

Secondary Outcome Measures :
  1. Remission [ Time Frame: at 28 weeks after randomization ]
    DAS28 CRP<2.6

  2. Remission [ Time Frame: at week 104 ]
    DAS28 CRP<2.6

  3. EULAR response [ Time Frame: at 28 weeks after randomization ]
  4. EULAR response [ Time Frame: at week 104 ]
  5. Health Assessment Questionnaire (HAQ) response [ Time Frame: at 28 weeks after randomization ]
    HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.

  6. Health Assessment Questionnaire (HAQ) response [ Time Frame: at week 104 ]
    HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.

  7. Radiographic progression [ Time Frame: at week 52 ]
  8. Radiographic progression [ Time Frame: at week 104 ]
  9. Analysis of reported (Serious) Adverse Reactions [ Time Frame: over 104 weeks ]
    (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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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-
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03649061


Locations
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Sponsors and Collaborators
P. Verschueren
Belgium Health Care Knowledge Centre
Investigators
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Principal Investigator: Patrick Verschueren, MD, PhD UZ Leuven
More Information
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Publications of Results:

Other Publications:

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Responsible Party: P. Verschueren, Prof. Dr., Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT03649061    
Other Study ID Numbers: KCE-16002
2017-004054-41 ( EudraCT Number )
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by P. Verschueren, Universitaire Ziekenhuizen Leuven:
COBRA-Slim
Accelerated access to anti-TNF
treat to target
remission induction
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Etanercept
Leflunomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
 Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action