A multicentre randomised trial of etanercept and methotrexate to induce remission in early inflammatory arthritis

ISRCTN ISRCTN55428162
DOI https://doi.org/10.1186/ISRCTN55428162
EudraCT/CTIS number 2005-005467-29
ClinicalTrials.gov number NCT01303874
Secondary identifying numbers RR05/7150
Submission date
25/10/2006
Registration date
30/04/2007
Last edited
10/09/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Paul Emery
Scientific

c/o Anne-Maree Keenan
Academic Unit of Musculoskeletal Disease
2nd Floor
Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom

Phone +44 (0)113 392 3043
Email A.Keenan@Leeds.ac.uk

Study information

Study designMulticentre, double blind, placebo -controlled randomised clinical trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA multicentre randomised trial of etanercept and methotrexate to induce remission in early inflammatory arthritis
Study acronymThe EMPIRE Trial (Etanercept and Methotrexate in Patients to Induce Remission in Early arthritis)
Study objectivesInduction therapy with Etanercept (ETN) in addition to Methotrexate (MTX) can induce sustained remission in patients with persistent early inflammatory arthritis.
Ethics approval(s)Approval received from the local Ethics Committee on the 30th March 2006 (ref: 06/Q1206/7).
Health condition(s) or problem(s) studiedEarly Inflammatory Arthritis
InterventionEtanercept and methotrexate versus placebo and methotrexate.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Etanercept, methotrexate
Primary outcome measureTo determine the number of patients in clinical remission at 12 months, as defined as the absence of symptoms and signs of inflammatory arthritis (i.e., Swollen Joint Count [SJC] zero; Tender Joint Count [TJC] zero).
Secondary outcome measures1. The number of patients in clinical remission at 18 months (as defined as absence of symptoms and signs of clinical arthritis i.e., SJC zero; TJC zero)
2. Conventional disease activity measures (Visual Analogue Scale [VAS] pain/fatigue/global/physician, Early Morning Stiffness (EMS), TJC, SJC, C-Reactive Protein [CRP], Erythrocyte Sedimentation Rate [ESR])
3. Functional, work and quality of life assessments (Health Assessment Questionnaire [HAQ], WIS, WDA, EuroQoL [EQ-5d] instrument, Short Form health survey [SF-36])
4. Proportion of patients achieving 26 weeks of remission
5. Disease Activity Score (DAS) 28
6. The number of patients in drug-free remission at 12 and 18 months
7. The number of patients in etanercept-free remission at 12 and 18 months (ETN arm)
8. Remission by American College of Rheumatology (ACR) criteria
9. To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change at 12 months and 18 months
Overall study start date19/10/2006
Completion date31/10/2008

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit80 Years
SexNot Specified
Target number of participants110
Key inclusion criteriaSubject must fulfill all of the following conditions or characteristics in order to be considered for study enrolment or participation:
1. Aged 18 to 80 years
2. Patients have articular synovitis, within three months of diagnosis (synovitis is defined as the presence soft tissue swelling and at least one of the following two criteria: tenderness or decreased range of motion)
3. Either Rheumatoid Factor (RF) antibody (positive) or Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibody (positive) or Shared Epitope (SE) (positive)
4. Demonstrates a negative serum pregnancy test at screening if female of childbearing potential. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Sexually active women participating in the study must use a medically acceptable form of contraception during the study and for three months after the last dose of study medications. Medically acceptable forms of contraception for women include oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception
5. Agrees to use a medically accepted form of contraception during the study and for three months after the last dose of study drug, if sexually active male. Medically acceptable forms of contraception for males are a properly used barrier contraceptive or sterilisation
6. Is capable of understanding and signing an informed consent form
7. Is able and willing to self-inject study drug or have a designee who can do so
8. Is able and willing to take oral medication
9. Is able to store injectable test article at 2°C to 8°C
10. Demonstrates a negative tuberculosis screening test
Key exclusion criteriaSubjects with any of the following conditions or characteristics will be excluded from study enrolment:
1. Received previous treatment with any Disease Modifying Anti-Rheumatic Drugs (DMARDs)
2. Received previous treatment with ETN or other Tumour Necrosis Factor (TNF) antagonist (e.g. a TNF monoclonal antibody or a soluble TNF receptor)
3. Previous treatment with Interleukin-1 (IL-1) receptor antagonist
4. Chronic arthritis diagnosed before 16 years old
5. Received any investigational ‘biological’ agent within three months of screening visit
6. Received treatment with any investigational drug of ‘chemical’ nature within one month prior to study screening
7. Known Human Immunodeficiency Virus (HIV)
8. Presence of any contraindication to ETN or MTX
9. Has significant concurrent medical diseases including uncompensated congestive heart failure, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, severe pulmonary disease, or history of Human Immunodeficiency Virus (HIV) infection, immunodeficiency syndromes, Central Nervous System (CNS) demyelinating events suggestive of multiple sclerosis, renal or gastrointestinal conditions, which in the opinion of the investigator places the subject at an unacceptable risk for participation in the study
10. Has cancer or a history of cancer (other than resected cutaneous basal cell carcinoma, and in situ cervical cancer) within five years of entering the screening period
11. Current crystal or infective arthritis
12. Chronic infection of the upper respiratory tract (e.g., sinusitis), chest (e.g., bronchiectatic lung disease), urinary tract or skin (e.g., paronychia, chronic ulcers, open wounds)
13. Any ongoing or active infection or any major episode of infection requiring hospitalisation or treatment with intravenous (IV) antibiotics within the preceding 30 days and/or orally administered antibiotics in the preceding 15 days
14. Demonstrates liver function abnormality (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] more than 2 x Upper Limit of Normal [ULN]) or bilirubin more than 51 µmol/L
15. Has renal disease (creatinine level more than 133 µmol/L)
16. Has leukopaenia (white blood cells less than 3000 x 10^6/L)
17. Has thrombocytopaenia (platelets less than 125 x 10^9/L)
18. Has a haemoglobin level of less than 9 g/L for males and less than 85 g/L for females
19. Is pregnant or breast-feeding
20. Joint surgery within preceding two months (at joints to be assessed within this study)
21. Received anti-CD4, diphtheria Interleukin-2 (IL-2) fusion protein, anti-Interleukin-6 (anti-IL-6), rituxamab or other immunosuppressive biologic during the last six months before screening, and treatment with such agents more than six months before screening if there are persistent signs of immunosuppression (with a subsequent abnormal absolute T-cell count) at screening visit
22. Received any live (attenuated) vaccines within four weeks of screening visit
23. Received cyclophosphamide within six months of screening visit
24. Any corticosteroids within 28 days prior to screening
25. Uses a dose of Non-Steroidal Anti-Inflammatory Drug (NSAID) greater than the maximum recommended dose in the product information at the screening visit
26. Has a history of confirmed blood dyscrasia
27. Has any condition judged by the physician to cause this study to be detrimental to the subject
28. Has a history of drug abuse or psychiatric disease that would interfere with the ability to comply with the study protocol
29. Has a history of alcohol abuse or excessive alcohol beverage consumption
30. Has a history of known liver cirrhosis, fibrosis, or fatty liver
31. Has a history of any viral hepatitis within one year of screening
Date of first enrolment19/10/2006
Date of final enrolment31/10/2008

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

c/o Anne-Maree Keenan
Leeds
LS7 4SA
United Kingdom

Sponsor information

University of Leeds (UK)
University/education

c/o Jonathan Gower
Senior Research Manager
Faculty of Medicine and Health, Room 7.11
Level 7 - Worsley Building
Clarendon Way
Leeds
LS2 9NL
England
United Kingdom

Phone +44 (0)113 343 3264
Email j.gower@leeds.ac.uk
Website http://www.leeds.ac.uk/
ROR logo "ROR" https://ror.org/024mrxd33

Funders

Funder type

Industry

Wyeth Pharmaceuticals Ltd (UK) - Investigator-initiated study funding grant

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/03/2010 Yes No
Results article results 01/06/2014 Yes No

Editorial Notes

10/09/2019: ClinicalTrials.gov number and EudraCT number added.