World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 19 March 2012
Main ID:  EUCTR2006-006186-16-NL
Date of registration: 16/07/2007
Prospective Registration: Yes
Primary sponsor: Leiden University Medical Center, department of rheumatology
Public title: IMPROVED: Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease A randomized clinical trial in patients with recent-onset arthritis to compare the efficacy of DMARD combination therapy including prednisone with combination therapy including adalimumab, a TNF-blocking agent - IMPROVED
Scientific title: IMPROVED: Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease A randomized clinical trial in patients with recent-onset arthritis to compare the efficacy of DMARD combination therapy including prednisone with combination therapy including adalimumab, a TNF-blocking agent - IMPROVED
Date of first enrolment: 30/01/2007
Target sample size:
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006186-16
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: yes Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no  
Phase: 
Countries of recruitment
Netherlands
Contacts
Name:    
Address: 
Telephone:
Email:
Affiliation: 
Name:    
Address: 
Telephone:
Email:
Affiliation: 
Key inclusion & exclusion criteria
Inclusion criteria:
1. minimum age of 18 years
2. at least one swollen joint
3. at least one other painful joint
4. symptom duration shorter than 2 years
5. diagnosis rheumatoid arthritis according to the ACR classification criteria or
6. diagnosis undifferentiated arthritis, suspected for rheumatoid arthritis by the rheumatologist, as no classification criteria exist.
7. patients naive for treatment with corticosteroids and disease modifying anti-rheumatic drugs (DMARDs).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. previous therapy with DMARDs or with corticosteroids (exception: one dose of parenteral corticosteroids within the last 6 months, but not within the last 2 months, or an oral dose of prednisone of =<10 mg/day for =< 2 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 (ASAT, ALAT > 3 times normal value)
7. serum creatinine level > 150 umol/l or estimated creatinine clearance of < 75%
8. uncontrolled diabetes mellitus (according to the rheumatologist)
9. uncontrolled hypertension or moderate to severe heart failure (NYHA class III/IV)
10. alcohol or drug abuse
11. history of infected joint prothesis within the previous 3 months
12. serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months
13. chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis
14. history of active tuberculosis requiring treatment within previous 3 years, or signs and symptoms of latent infection with tuberculosis, based on medical history, physical examination, tuberculin (PPD) skin test or chest radiograph (see 9.3.1).
15. history of other granulomatous infections as histoplasmosis or coccidiomycosis
16. evidence of active cytomegalovirus, active pneumocystis carinii, active aspergillosis, or drug resistant atypical mycobacterium infection
17. history of opportunistic infections such as herpes zoster within previous 2 months.
18. history of active hepatitis B infection or evidence of a latent infection (see 9.3.1).
19. documented HIV infection, AIDS related complex (ARC) or AIDS.
20. history of lymphoproliferative disease including lymphoma or signs suggestive of possible lymphoproliferative disease.
21. Multiple sclerosis or neurological symptoms suspect for demyelinising disease.
22. Hypersensitivity to human immunoglobuline or other constituents of adalimumab



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
rheumatoid arthritis and undifferentiated arthritis
MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Intervention(s)

Product Name: Methotrexate
Product Code: MTX
Pharmaceutical Form: Tablet
INN or Proposed INN: METHOTREXATE
CAS Number: 59052
Current Sponsor code: MTX
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 30-

Product Name: Prednisone
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
CAS Number: 53032
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 7,5-60

Product Name: Sulfasalazine
Pharmaceutical Form: Tablet
INN or Proposed INN: SULFASALAZINE
CAS Number: 599791
Current Sponsor code: SSZ
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 2000-

Trade Name: hydroxychloroquine
Product Name: hydroxychloroquine
Product Code: HCQ
Pharmaceutical Form: Tablet
INN or Proposed INN: HYDROXYCHLOROQUINE SULFATE
CAS Number: 747364
Current Sponsor code: HCQ
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 400-

Trade Name: Humira
Product Name: adalimumab
Pharmaceutical Form: Solution for injection

Primary Outcome(s)
Main Objective: The objectives of this study are:
•To determine the percentage of patients with recent-onset RA and UA who achieve and maintain clinical remission on treatment with a combination of methotrexate 25 mg/week and extended prednisone pulse (tapered high dose) after 4 months.

•To determine whether, if clinical remission is not achieved, methotrexate+prednisone combination therapy should be extended with sulphasalazine and hydroxychloroquine or switched to methotrexate+adalimumab combination therapy.
Primary end point(s): Clinical remission according to a disease activity score (DAS) < 1.6, measured by research nurses at each follow-up visit. The percentage of patients achieving clinical remission after 4 months with the initial therapy consisting of MTX and tapered high dose prednisone will be calculated. From the patients who were randomized to one of two treatment arms, the percentage achieving clinical remission after one year will be calculated.

Functional ability will be measured by the Dutch Health Assessment Questionnaire (HAQ), a self-administered questionnaire that evaluates the level of difficulty the patient is experiencing with activities of daily living (ADL) and the degree of assistance required by the patient.

Radiological joint damage, absolute as well as progression from baseline, will be assessed on radiog¬raphs of the hands, wrists and feet at entry and one year later by the validated modified Sharp/van der Heijde score All radio¬graphs will be sent to the coordi¬na¬ting centre and viewed separate by two experienced rheumatologists, who are blinded for the treatment allocation. The radiographs will be presented in random order.
Secondary Objective: toxicity, costs, quality of life measurements
Secondary Outcome(s)
Secondary ID(s)
IMPROVED
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history