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

ISRCTN	ISRCTN48638981
DOI	https://doi.org/10.1186/ISRCTN48638981
Secondary identifying numbers	RR05/7092

Submission date: 25/10/2006
Registration date: 30/04/2007
Last edited: 19/09/2016

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 James Goulding
Academic Unit of Musculoskeletal Disease
2nd Floor, Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom

Phone	+44 (0)113 392 3043
Email	J.T.R.Goulding@leeds.ac.uk

Study information

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
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
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
Study acronym	IDEA (Infliximab as inDuction therapy in Early rheumatoid Arthritis)
Study objectives	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(s)	Northern and Yorkshire Multi-Centre Research Ethics Committee,06/04/2006, ref: 05/MRE03/85
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Infliximab, methotrexate, steroid
Primary outcome measure	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 study start date	26/09/2006
Completion date	30/09/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	80 Years
Sex	Both
Target number of participants	112
Key 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
Key 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
Date of first enrolment	26/09/2006
Date of final enrolment	30/09/2007

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Chapel Allerton Hospital

Leeds
LS7 4SA
United Kingdom

Sponsor information

University of Leeds (UK)
University/education

c/o Johnathan Gower
Senior Research Manager
Faculty if 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"	https://ror.org/024mrxd33

Funders

Funder type

Industry

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

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/01/2014		Yes	No
Results article	results	01/12/2016		Yes	No

Editorial Notes

19/09/2016: Publication reference added.