Condition category
Musculoskeletal Diseases
Date applied
12/09/2005
Date assigned
12/09/2005
Last edited
23/08/2011
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 M. Boers

ORCID ID

Contact details

VU University Medical Center
PK 6Z 185
Department of Clinical Epidemiology and Biostatistics
Amsterdam
1007 MB
Netherlands
+31 (0)20 4444474
keb.info@vumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

P03627; NTR80

Study information

Scientific title

Acronym

Study hypothesis

In 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

The Ethics Review board of the Vrije University Medical Center has approved this protocol (reference number 2003-186).

Study design

Double blinded randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Rheumatoid arthritis

Intervention

The 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 type

Other

Phase

Not Specified

Drug names

Primary outcome measures

1. 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 measures

1. 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 trial start date

01/10/2004

Overall trial end date

30/09/2006

Reason abandoned

Eligibility

Participant inclusion criteria

Patients 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

1. 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)

Recruitment start date

01/10/2004

Recruitment end date

30/09/2006

Locations

Countries of recruitment

Netherlands

Trial participating centre

VU University Medical Center
Amsterdam
1007 MB
Netherlands

Sponsor information

Organisation

Vrije University Medical Centre (VUMC) (The Netherlands)

Sponsor details

Departments of Clinical Epidemiology and Biostatistics and Rheumatology
P.O. Box 7057
Amsterdam
1007 MB
Netherlands
+31 (0)20 444 4474
keb.info@vumc.nl

Sponsor type

University/education

Website

http://www.vumc.nl/zorg/

Funders

Funder type

Industry

Funder name

Schering-Plough (The Netherlands)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

Vrije University Medical Centre (VUMC) (The Netherlands)

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

Results in http://www.ncbi.nlm.nih.gov/pubmed/18625629

Publication citations

  1. Results

    van Tuyl LH, Lems WF, Voskuyl AE, Kerstens PJ, Garnero P, Dijkmans BA, Boers M, Tight control and intensified COBRA combination treatment in early rheumatoid arthritis: 90% remission in a pilot trial., Ann. Rheum. Dis., 2008, 67, 11, 1574-1577, doi: 10.1136/ard.2008.090712.

Additional files

Editorial Notes