Condition category
Musculoskeletal Diseases
Date applied
25/10/2006
Date assigned
30/04/2007
Last edited
19/09/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Paul Emery

ORCID ID

Contact details

c/o James Goulding
Academic Unit of Musculoskeletal Disease
2nd Floor
Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom
+44 (0)113 392 3043
J.T.R.Goulding@leeds.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RR05/7092

Study information

Scientific title

A multicentre randomised double-blind placebo-controlled study comparing two regimens of combination induction therapy in early disease-modifying anti-rheumatic drug naïve rheumatoid arthritis

Acronym

IDEA (Infliximab as inDuction therapy in Early rheumatoid Arthritis)

Study hypothesis

To compare the efficacy of biologic therapy (infliximab) as induction therapy against current best practice therapy: early introduction of methotrexate in combination with steroid induction therapy and dose modification according to pre-defined disease activity measures.

Ethics approval

Northern and Yorkshire Multi-Centre Research Ethics Committee,06/04/2006, ref: 05/MRE03/85

Study design

Multicentre double-blind placebo-controlled randomised clinical trial for 6 months followed by open-label observation period of treatment strategy

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Early rheumatoid arthritis

Intervention

Infliximab arm:
1. Methotrexate (10 mg, increasing to 20 mg by six weeks) orally once a week for the treatment period of the trial (18 months)
2. Infliximab (3 mg/kg) intravenous (IV) infusion at baseline, week two, week six and then eight-weekly) for the treatment period of the trial (18 months)

Steroid/placebo arm:
1. Methotrexate (10 mg, increasing to 20 mg by six weeks) orally once a week for the treatment period of the trial (18 months)
2. Methylprednisolone (250 mg IV infusion at baseline)
3. Placebo (250 ml 9 mg/l NaCl at weeks two, six, 14 and 22)

N.B.: These regimens are subject to modification depending upon patient response.

Intervention type

Drug

Phase

Not Applicable

Drug names

Infliximab, methotrexate, steroid

Primary outcome measures

Change in Sharpe van Der Heijde score at 50 weeks.

Secondary outcome measures

Secondary outcomes in this study include changes in clinical response over 18 months as measured by:
1. The number of patients having a major clinical response (DAS less than 1.6 maintained for six months)
2. The change in Sharpe van Der Heijde scores between baseline and 26 and 78 weeks
3. The number of patients in clinical remission (DAS less than 1.6) at 78 weeks
4. The number of patients in clinical remission (DAS less than 1.6) at 78 weeks, no longer on infliximab/placebo infusions
5. The number of patients in clinical remission (DAS less than 1.6) at 26 weeks
6. Rheumatoid Arthritis Quality of Life Questionnaire (RA QoL)
7. Health Assessment Questionnaire
8. Immunogenetic studies to predict long-term immune response
9. Immune phenotyping (flow cytometry) and assessment of immune effector and regulatory functions
10. Assessment of serum and plasma markers to predict response to therapy and vascular function

Overall trial start date

26/09/2006

Overall trial end date

30/09/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Men and women 18 to 80 years of age
2. Fulfil 1987 American College of Rheumatology (ACR) Criteria for rheumatoid arthritis (RA)
3. Symptoms of more than three months and less than 12 months duration
4. Men and women must use adequate birth control measures (e.g., abstinence, oral contraceptives, intra-uterine device, barrier method with spermicide, or surgical sterilisation) for the duration of the study and should continue such precautions for six months after receiving the last infusion or dose of methotrexate
5. The patient must be able to adhere to the study visit schedule and other protocol requirements
6. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
7. Must have a chest radiograph within three months prior to first treatment dose with no evidence of malignancy, infection or fibrosis
8. Are considered eligible according to the tuberculosis (TB) eligibility assessment, screening, and early detection of reactivation rules defined in the protocol
9. Active disease as defined by Disease Activity Score (DAS) more than 2.4
10. Tumour necrotising factor (TNF) therapy naïve
11. Disease-modifying anti-rheumatic drug (DMARD) therapy naïve
12. Negative hepatitis B and C screening tests within three months prior to screening visit

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

112

Participant exclusion criteria

1. Women who are pregnant, nursing, or men or women planning pregnancy within 24 months after screening (i.e., approximately six months following last study medications)
2. Use of any investigational (unlicensed) drug within one month prior to screening or within five half-lives of the investigational agent, whichever is longer
3. Previous or current treatment with any other therapeutic agent targeted at reducing TNF (e.g., pentoxifylline, thalidomide, etanercept, infliximab, adalimumab etc.)
4. Prior treatment with any DMARD
5. Serious infections (such as pneumonia or pyelonephritis) in the previous three months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator
6. Documented human immunodeficiency virus (HIV) infection
7. Hepatitis B or hepatitis C serology positive (must be checked within three months prior to screening)
8. Are considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in the protocol
9. Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within six months prior to screening
10. Significant haematological or biochemical abnormality:
10.1. Haemoglobin less than or equal to 8.5 g/dL
10.2. White blood cells (WBC) less than or equal to 3.5 x 10^9/L
10.3. Neutrophils less than or equal to 1.5 x 10^9/L
10.4. Platelets less than or equal to 100 x 10^9/L
10.5. Alanine aminotransferase (ALT) more than two times upper limit of normal (ULN) for the laboratory conducting the test
10.6. Creatinine more than 1.5 times ULN for the laboratory conducting the test
11. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis)
12. Concomitant congestive heart failure, including medically controlled asymptomatic patients
13. Presence of a transplanted organ (with the exception of a corneal transplant more than three months prior to screening)
14. Malignancy within the past five years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence)
15. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly
16. Known recent substance abuse (drug or alcohol)
17. Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period
18. Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB as described in the protocol
19. Have a positive Mantoux test or evidence of active TB infection, or recent close contact with an individual with active TB
20. Previous oral, intramuscular (IM), intra-arterial (IA) or intravenous (IV) corticosteroids within one month
21. Receiving treatment with anakinra
22. Contraindications to methotrexate, infliximab or steroids

Recruitment start date

26/09/2006

Recruitment end date

30/09/2007

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Chapel Allerton Hospital
Leeds
LS7 4SA
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

c/o Johnathan Gower
Senior Research Manager
Faculty if Medicine and Health
Room 7.11
Level 7 - Worsley Building
Clarendon Way
Leeds
LS2 9NL
United Kingdom
+44 (0)113 343 3264
j.gower@leeds.ac.uk

Sponsor type

University/education

Website

http://www.leeds.ac.uk/

Funders

Funder type

Industry

Funder name

Schering-Plough Ltd (UK) - Investigator-initiated study funding grant

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/23912798
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27638812

Publication citations

  1. Results

    Nam JL, Villeneuve E, Hensor EM, Conaghan PG, Keen HI, Buch MH, Gough AK, Green MJ, Helliwell PS, Keenan AM, Morgan AW, Quinn M, Reece R, van der Heijde DM, Wakefield RJ, Emery P, Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study)., Ann. Rheum. Dis., 2014, 73, 1, 75-85, doi: 10.1136/annrheumdis-2013-203440.

Additional files

Editorial Notes

19/09/2016: Publication reference added.