Treatment intensification based on disease activity parameters or on cartilage breakdown markers in early rheumatoid arthritis

ISRCTN ISRCTN96372677
DOI https://doi.org/10.1186/ISRCTN96372677
Secondary identifying numbers P03627; NTR80
Submission date
12/09/2005
Registration date
12/09/2005
Last edited
23/08/2011
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 M. Boers
Scientific

VU University Medical Center
PK 6Z 185
Department of Clinical Epidemiology and Biostatistics
Amsterdam
1007 MB
Netherlands

Phone +31 (0)20 4444474
Email keb.info@vumc.nl

Study information

Study designDouble blinded randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific title
Study objectivesIn early rheumatoid arthritis (RA), does treatment intensification (by conventional and biological means) aimed at keeping urine CTX-2 levels below 150 nmol/µmol creatinine lead to a lower radiological progression than treatment intensification aimed at keeping DAS28 at or below 3.2?
Ethics approval(s)The Ethics Review board of the Vrije University Medical Center has approved this protocol (reference number 2003-186).
Health condition(s) or problem(s) studiedRheumatoid arthritis
InterventionThe study design randomises to two monitoring strategies that lead to subsequent steps in the treatment schedule: either clinical monitoring by DAS28 to achieve and keep the DAS below 2.6 (clinical remission); or: lab monitoring by CTX-2 to achieve and keep the urinary level of CTX-2 below 150 ng/µmol creatinine.

All patients will receive 'traditional' combination DMARD therapy for a minimum of 22 weeks: step 1 is evaluated at week 8, and step 2 at week 22. Patients will receive treatment intensification according to achieved levels of DAS28 (DAS group) or according to achieved levels of CTX-2 (CTX group).
Intervention typeOther
Primary outcome measure1. DAS28: Disease activity score calculated from swollen and tender joint counts, erythrocyte sedimentation rate (ESR), patient global assessment of disease activity (10 cm Visual Analogue Scale [VAS])
2. CTX-2: measured in spot urine (delivered 1 week before visit) together with creatinine (method Garnero, Lyon)
Secondary outcome measures1. WHO/ILAR core set; DAS remission, EULAR improvement; ACR remission, ACR20,etc; EuroQoL
2. Efficacy self assessment: RADAI joint score, fatigue VAS
3. Bone Mass: DEXA lumbar spine; Right hip (neck)
Overall study start date01/10/2004
Completion date30/09/2006

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants40
Key inclusion criteriaPatients must have:
1. Rheumatoid arthritis (American College of Rheumatology [ACR] criteria met cumulatively)
2. Requiring treatment: 28-item Disease Activity Score (DAS28) greater than 3.2
3. Propensity for radiographic progression: urinary CTX-2 greater than 150 ng/µmol creatinine
Key exclusion criteria1. Unwillingness to participate in the study and comply with its procedures by signing a written informed consent

More chance of harm:
2. Contraindication to study drugs:
2.1. Previous serious adverse reaction or documented allergy to any of the trial drugs or their constituents
2.2. Previous inability to tolerate sulphasalazine (minimum 1 g/d), hydroxychloroquine (minimum 200 mg/d) methotrexate (minimum 7.5 mg/week) or oral prednisolone
3. Active infection or those at high risk of infection:
3.1. Abnormal chest X-ray or positive tuberculin test suggestive of previous TB that has not been adequately treated
3.2. Chronic leg ulcers
3.3. Septic arthritis of a native joint within the last 12 months
3.4. Previous prosthetic joint sepsis within the last 12 months, indefinitely if prosthesis remains in situ
3.5. Bronchiectasis, indwelling urinary catheter and other situation deemed high risk by treating physician
4. Malignancy, excluding basal cell carcinoma and malignancies diagnosed and treated more than 10 years previously, in whom there is a high probability of cure in the opinion of the treating physician
5. Pregnancy, planned pregnancy or lactation. Women of childbearing age (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed intrauterine device [IUD], condom in combination with spermicide) or be surgically sterilised (e.g., hysterectomy or tubal ligation)
6. Current signs or symptoms of severe, progressive, or uncontrolled renal, haematological, hepatic, respiratory, gastrointestinal, endocrine, cardiac, neurological or cerebral disease. Specifically, this includes cardiac failure (New York Heart Association [NYHA] class 3 or 4)
7. Screening blood tests at baseline which show haemoglobin less than 8 g/l, total white blood cell count (WBC) less than 3.5 or neutrophils less than 1.5, platelets less than 100. Patients will also be excluded if serum alanine aminotransferase (ALT) or alkaline phosphatase are more than twice the upper limit of normal, or impaired renal function: creatinine greater than 100 mumol/L AND Cockroft creatinine clearance less than 40 ml/min
8. Subjects who have used any investigational product within 30 days prior to enrolment
9. Aged less than 18 years

Less chance of benefit:
10. Disease duration greater than 36 months (date of diagnosis by rheumatologist
11. Previous treatment of RA with more than two disease modifying anti-rheumatic drugs (DMARDs). Systemic glucocorticoids are counted as DMARDs. Treatment is defined as a cumulative period of 8 weeks or more.

Measurement difficulties:
12. Insufficient command of local language
13. Illiteracy
14. Inability to comply with the protocol (opinion of treating physician)
Date of first enrolment01/10/2004
Date of final enrolment30/09/2006

Locations

Countries of recruitment

  • Netherlands

Study participating centre

VU University Medical Center
Amsterdam
1007 MB
Netherlands

Sponsor information

Vrije University Medical Centre (VUMC) (The Netherlands)
University/education

Departments of Clinical Epidemiology and Biostatistics and Rheumatology
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Phone +31 (0)20 444 4474
Email keb.info@vumc.nl
Website http://www.vumc.nl/zorg/
ROR logo "ROR" https://ror.org/00q6h8f30

Funders

Funder type

Industry

Schering-Plough (The Netherlands)
Private sector organisation / For-profit companies (industry)
Location
United States of America
Vrije University Medical Centre (VUMC) (The Netherlands)

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 01/11/2008 Yes No