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Very Early Versus Delayed Etanercept in Patients With RA (VEDERA)

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ClinicalTrials.gov Identifier: NCT02433184
Recruitment Status : Completed
First Posted : May 4, 2015
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Dr Maya Buch, University of Leeds

Brief Summary:
The main aim of the study is to determine whether TNFi instituted as first-line therapy in early RA confers better outcomes (clinical, structural and immunological) compared to delayed TNFi start; implying particular dominance of TNF in early disease, a changing role of TNF with disease duration and hence, confirmation of a biological window of opportunity.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Etanercept Drug: Methotrexate Drug: Sulfasalazine Drug: Hydroxychloroquine Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Single-centre, Randomised Study Evaluating the Clinical, Imaging and Immunological Depth of Remission Achieved by Very Early Versus Delayed Etanercept in Patients With Rheumatoid Arthritis
Actual Study Start Date : July 2011
Actual Primary Completion Date : August 2017
Actual Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Etanercept

Arm Intervention/treatment
Experimental: Etanercept
Treatment Arm 1 will receive etanercept and methotrexate combination therapy administered for a total duration of 48 weeks.
Drug: Etanercept
Etanercept will be administered subcutaneously at a dose of 50 mg weekly and will be discontinued at the primary endpoint (48 weeks).

Drug: Methotrexate
Methotrexate will be administered orally at a starting dose of 15 mg weekly, increasing to 20mg and 25mg weekly at weeks 4 and 8 respectively.

Active Comparator: Methotrexate-treat to target
Treatment Arm 2 will receive initial methotrexate monotherapy with adoption of a treat to target protocol (standard care involving monthly DAS28-ESR assessment with escalation to combination sDMARD therapy if not achieving LDA at, or after, 8 weeks) and step-up to etanercept and methotrexate at 24 weeks if failing to achieve clinical remission
Drug: Methotrexate
Methotrexate will be administered orally at a starting dose of 15 mg and will be increased to 25mg weekly at 2 weeks.

Drug: Sulfasalazine
Sulfasalazine will be added at weeks 8,12,16 or 20 if the subject fails to achieve low disease activity, administered orally at a dose of 1g twice daily. Will be discontinued if starting etanercept at 24 weeks.

Drug: Hydroxychloroquine
Hydroxychloroquine will be added at weeks 8,12,16 or 20 if the subject fails to achieve low disease activity, administered at a dose of 200mg daily. Will be discontinued if starting etanercept at 24 weeks.

Drug: Etanercept
Etanercept will be added at 24 weeks, if a subject fails to achieve clinical remission,at a dose of 50 mg weekly and will be discontinued at 48 weeks with the exception of those patients who are eligible to continue according to local prescribing guidelines (NICE guidelines)




Primary Outcome Measures :
  1. Clinical remission [ Time Frame: 48 weeks ]
    Proportion of patients that achieve clinical remission (Disease activity Score, DAS28 <2.6) at 48 weeks, following either treatment strategy.


Secondary Outcome Measures :
  1. Change in MRI synovitis [ Time Frame: baseline and week 48 ]
    Change in MRI synovitis between baseline and 48 weeks.

  2. CDAI (clinical disease activity index) [ Time Frame: weeks 12, 24, 48 and 96 ]
    Change in CDAI score from baseline at weeks 12, 24, 48 and 96

  3. SDAI (simplified disease activity index) [ Time Frame: weeks 12, 24, 48 and 96 ]
    Change in SDAI score from baseline at weeks 12, 24, 36 & 48.

  4. ACR(American College of Rheumatology) response scores [ Time Frame: weeks 12, 24, 48 and 96 ]
    ACR response score from baseline at weeks 12, 24, 48 and 96

  5. EULAR(European League Against Rheumatism)response criteria [ Time Frame: weeks 12, 24, 48 and 96 ]
    EULAR response score from baseline

  6. Physical function, assessed by HAQ(health assessment questionnaire) [ Time Frame: weeks 12, 24, 48 and 96 ]
  7. Quality of life scores assessed by RA-QoL(RA quality of life questionnaire) [ Time Frame: weeks 12, 24, 48 and 96 ]
  8. Work instability, assessed by RA-WIS(RA work instability questionnaire) [ Time Frame: weeks 12, 24, 48 and 96 ]
  9. HRUS (High Resolution Ultrasound) [ Time Frame: weeks 0, 12, 24 and 48 ]
    Change in HRUS from baseline

  10. Radiographic scores [ Time Frame: weeks 48 and 96 ]
    Change in joint damage assessed by modified Sharp score.

  11. Immunological parameters in blood sample [ Time Frame: weeks 0, 12, 24 and 48 ]
    Change in immunological markers of inflammation between baseline and weeks 12, 24 and 48.

  12. Immunological parameters in synovial tissue [ Time Frame: weeks 0, 24, +/- 48 ]
    Change in immunological markers of inflammation between baseline and weeks 24 and 48.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients aged between 18 and 80 years.
  • Diagnosis of rheumatoid arthritis (new 2010 ACR/EULAR RA classification criteria).
  • Symptom onset within the preceding 12 months.
  • Patients with active RA at baseline: clinical evidence of synovitis (or imaging evidence of synovitis in cases of uncertainty/subclinical disease) in hand and/or wrist joints evaluable by ultrasound and MRI, and DAS28-ESR>3.2.
  • Seropositivity for anti-citrullinated peptide antibody (ACPA) and/or rheumatoid factor. If ACPA and rheumatoid factor are both negative, presence of power Doppler in at least 1 joint on ultrasound imaging.
  • DMARD-naive (with the exception of previous exposure to hydroxychloroquine for an indication other than RA).
  • All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives.

Exclusion Criteria:

  • Previous treatment with DMARDs for the management of RA.
  • Intramuscular or intra-articular (of non-target joint) corticosteroid within 28 days of the screening visit; intra-articular steroid of the chosen target joint within 12 weeks of screening.
  • Oral steroid of greater than 10mg prednisolone daily, or change in oral steroid dose within 28 days of study drug initiation at the baseline visit.
  • Use (including use as required) of more than one NSAID, change in NSAID or change in dose of NSAID within 28 days of the baseline visit.
  • Contraindications to MRI (e.g. pacemaker) or unable or unwilling to attend for all imaging assessments. In patients with previous penetrating trauma to the eye, or patients at high risk of previous metal foreign body injury to the eye (e.g. welding), skull x-ray will be performed; these patients may be included in the absence of residual metal fragments on x-ray.
  • Pregnancy or breastfeeding.
  • Other contraindications to TNFi as determined by local prescribing guidelines and physician discretion, including:

    • Active infection, open leg ulcers, previously infected prosthetic joint (unless completely removed), septic arthritis in last year, HIV, Hepatitis B or Hepatitis C carriers, previous malignancy within 10 years (except basal cell carcinoma), severe heart failure (New York Heart Association grade 3 or more), any history of demyelinating disease, uncontrolled diabetes, pulmonary fibrosis, bronchiectasis, previous PUVA therapy (of >1000 Joules), history of TB or evidence of latent TB on chest x-ray/TB testing (in the latter event, a patient may be included if treated with isoniazid and pyridoxine one month before starting the study and for a further 6 months whilst on study treatments).
  • History of other significant medical conditions, including:

    • Severe pulmonary disease, defined as requiring previous hospital admission or supplemental oxygen.
    • Active or severe cardiovascular disease: uncontrolled hypertension, myocardial infarction within 12 months of screening, unstable angina within 6 months of screening.
    • Other immunodeficiency disorders.
    • Connective tissue diseases, e.g. primary Sjogren's syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis.
    • Psoriasis.
    • Renal impairment (creatinine ≥ 175µmol/L).
    • Blood disorders: neutropenia (neutrophils < 2.0 x 109/L), thrombocytopenia (platelets < 125 x 109/L), or anaemia (haemoglobin < 8 g/dL).
    • Abnormal liver function (alanine transaminase, ALT > 3 x upper limit of normal).
  • Planned surgery within the study period which is expected to require omission of any study medication of 28 days or more.

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): NCT02433184


Locations
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United Kingdom
Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital
Leeds, West Yorkshire, United Kingdom, LS7 4SA
Sponsors and Collaborators
University of Leeds

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr Maya Buch, NIHR Clinician Scientist, Senior Lecturer/Honorary Consultant Rheumatologist, University of Leeds
ClinicalTrials.gov Identifier: NCT02433184     History of Changes
Other Study ID Numbers: RR10/9592
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019
Keywords provided by Dr Maya Buch, University of Leeds:
Etanercept
treat to target
Disease Modifying Antirheumatic Drugs (DMARDs)
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
Hydroxychloroquine
Sulfasalazine
Etanercept
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics