Induction therapy with methotrexate and prednisone in rheumatoid or very early arthritic disease

ISRCTN	ISRCTN11916566
DOI	https://doi.org/10.1186/ISRCTN11916566
EudraCT/CTIS number	2006-006186-16
Secondary identifying numbers	1

Submission date: 28/12/2006
Registration date: 28/12/2006
Last edited: 07/03/2018

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

Dr C F Allaart
Scientific

Leiden University Medical Center (LUMC)
Department of Rheumatology, C1-39
PO Box 9600
Leiden
2300 RC
Netherlands

Phone	+31 (0)71 526 3598
Email	c.f.allaart@lumc.nl

Study information

Study design	Randomised controlled parallel-group single-blinded multicentre trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	IMPROVED: Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease
Study acronym	IMPROVED
Study objectives	There is a clinically and statistically significant difference in the percentage of patients who achieve and maintain clinical remission (defined as Disease Activity Score [DAS] less than 1.6) and in functional ability and progression of radiological joint damage after one year of follow-up in recent-onset arthritis patients (Rheumatoid Arthritis [RA] and Undifferentiated Arthritis [UA]) who, having failed to achieve remission on a combination of methotrexate and a tapered high dose of prednisone, receive extended medication in a combination of methotrexate, sulphasalazine, hydroxychloroquine and low dose prednisone, or who switch to a combination of methotrexate and adalimumab.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Rheumatoid arthritis, undifferentiated arthritis
Intervention	Four-monthly evaluations of Disease Activity Score and safety. Medication adjustments by protocol, based on DAS calculation, aimed at DAS less than 1.6 (remission). Initial treatment with Methotrexate (MTX) and a tapered high dose of prednisone. If DAS more than 1.6, randomisation to either combination with MTX, Sulphasalazine (SSA), hydroxychloroquine and a tapered high dose of prednisone, or combination with MTX with adalimumab. In case of DAS less than 1.6: taper medication and discontinue if DAS remains less than 1.6.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Methotrexate, prednisone, sulphasalazine, adalimumab, hydroxychloroquine
Primary outcome measure	1. Percentage of patients in remission (DAS less than 1.6) 2. Functional ability as measured by Health Assessment Questionnaire (HAQ) 3. Radiological damage progression as measured by Sharp/van der Heijde score
Secondary outcome measures	1. Quality of life, as measured with McMaster-Toronto Arthritis (MACTAR), Short Form health survey (SF-36), EuroQol questionnaire 2. Time-trade-off 3. Costs 4. ACR arthritis core-set
Overall study start date	01/01/2007
Completion date	01/07/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	535
Key inclusion criteria	1. Patients more than or equal to 18 years of age with either RA according to the revised criteria of the American College of Rheumatology (ACR) of less than two years duration, or UA, suspected by the rheumatologist to have an early presentation of RA 2. All patients must have at least one (out of 66) swollen joint and at least one other (out of 68) painful joint, and a combined DAS of more than 1.6 3. All patients must be Disease Modifying Anti-Rheumatic Drugs (DMARDs) and corticosteroid naÏve
Key exclusion criteria	1. Previous therapy with DMARDs or with corticosteroids (exception: one dose of parenteral corticosteroids within the last six months, but not within the last two months, or an oral dose of prednisone of less than or equal to 10 mg/day for less than or equal to two weeks within the same period allowed) 2. Pregnancy or wish to become pregnant during the study, or childbearing potential without adequate contraception 3. Concomitant treatment with another experimental drug 4. History or presence of malignancy within the last five years 5. Bone marrow hypoplasia 6. Elevated hepatic enzyme levels (Aspartate Aminotransferase [AST], Alanine Aminotransferase [ALT] more than three times normal value) 7. Serum creatinine level more than 150 umol/l or estimated creatinin clearance of less than 75% 8. Uncontrolled diabetes mellitus (according to the rheumatologist) 9. Uncontrolled hypertension (according to the rheumatologist) 10. Heart failure (New York Heart Association [NYHA] functional class III or IV) 11. Alcohol or drug abuse 12. History of infected joint prothesis within the previous three months 13. Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous three months 14. Chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis 15. History of active tuberculosis requiring treatment within previous three years, or signs and symptoms of latent infection with tuberculosis, based on medical history, physical examination, Purified Protein Derivative (PPD) skin test, X-thorax 16. History of opportunistic infections such as herpes zoster within previous two months 17. Evidence of active cytomegalovirus, active pneumocystis carinii, or drug resistant atypical mycobacterium infection etc 18. Evidence of hepatitis B infection 19. Documented Human Immunodeficiency Virus (HIV) infection, Acquired Immune Deficiency Syndrome (AIDS) of AIDS Related Complex (ARC) 20. History of lymphoproliferative disease including lymphoma or signs suggestive of possible lymphoproliferative disease 21. Multiple sclerosis or neurological symptoms suspect for demyelinising disease
Date of first enrolment	01/01/2007
Date of final enrolment	01/07/2009

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Center (LUMC)

Leiden
2300 RC
Netherlands

Sponsor information

Leiden University Medical Center (LUMC) (The Netherlands)
Hospital/treatment centre

Department of Rheumatology
PO Box 9600
Leiden
2300 RC
Netherlands

Website	http://www.lumc.nl/english/start_english.html#http://www.lumc.nl/english/start_english.html
"ROR"	https://ror.org/05xvt9f17

Funders

Funder type

Industry

Abbott (The Netherlands)

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	Peer reviewed?	Patient-facing?
Results article	results	01/09/2012	Yes	No
Results article	results	01/12/2013	Yes	No
Results article	results	01/07/2014	Yes	No
Results article	results	15/02/2016	Yes	No
Results article	results	30/09/2017	Yes	No
Results article	results	26/02/2018	Yes	No

Editorial Notes

07/03/2018: Publication reference added.
02/10/2017: Publication reference added.
01/03/2016: Publication reference added.