Contact information
Type
Scientific
Primary contact
Mrs Debby den Uyl
ORCID ID
Contact details
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
+31 (0)20 444 3981
d.denuyl@vumc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2007/150; NTR1213
Study information
Scientific title
Combination therapy with rheumatoid arthritis (COBRA)-light study, an open randomised trial comparing a modified COBRA therapy with the COBRA therapy according to treatment strategies for rheumatoid arthritis (BeSt) in early rheumatoid arthritis
Acronym
COBRA-light
Study hypothesis
Early, aggressive treatment of rheumatoid arthritis (RA) with disease modifying anti-rheumatic drugs (DMARDs) has been proven to lower disease activity and suppress radiologic progression. Moreover, combination therapy is shown to be superior to monotherapy. The combination therapy with rheumatoid arthritis (COBRA) therapy is effective in several trials, and the positive effect on radiologic progression sustained over time. In a recent trial (BeSt [treatment strategies for Rheumatoid Arthritis] = see http://www.controlled-trials.com/ISRCTN32675862 for more details of this trial) comparing different treatment strategies the COBRA therapy and initial therapy with infliximab (a tumour necrotising factor [TNF]-blocker) were equally effective in improving functional ability and preventing radiographic damage. Apparently most rheumatologists and or patients have resistance in prescribing this therapy.
Ethics approval
METC VUmc-Amsterdam (The Netherlands), 06/09/2007, ref: 2007/150
Study design
Open randomised active-controlled parallel-group multicentre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Rheumatoid arthritis
Intervention
Participants will be randomly allocated to the two treatment strategies, i.e., COBRA or a modified COBRA schedule (COBRA-light):
COBRA:
Prednisone 60 mg/day, methotrexate 7.5 mg/wk and sulphasalazine (SSZ) 500 mg/day. Prednisone will be tapered to 7.5 mg/day in 7 weeks and in 28 weeks tapered to zero. SSZ will be increased to 2000 mg/day in 3 weeks.
COBRA-light:
Prednisone 30 mg/day, methotrexate 10 mg/wk. After 9 weeks prednisone will be tapered till 7.5 mg/day and methotrexate increased to 25 mg/week.
If patients have an active disease at week 26 or 39, anti-TNF therapy will be started in both treatment arms.
For both treatment arms the total treatment duration is one year with a second follow-up year. In the first year patients will be seen frequently in order to follow disease-activity, side effects and cardiovascular parameters. In the first year patients will be seen at 2, 4, 8, 13, 26, 39 and 52 weeks. Treatment will be adjusted according to the 44-item disease activity scale (DAS44) score. In the follow-up period of the second year patients will be seen every six months.
Intervention type
Drug
Phase
Not Applicable
Drug names
Methotrexate, sulphasalazine, prednisolone
Primary outcome measure
Difference in delta DAS compared at baseline between the both treatment strategies after six months.
Secondary outcome measures
1. Difference in delta DAS compared with baseline between the treatment strategies after 12 months
2. % patients with ACR 20, 50, 70 response
3. Low disease status (DAS 44 less than 2.4)
4. Health Assessment Questionnaire (HAQ) - delta Sharp van der Heijde score
5. % patients with radiological remission
6. Number of patients started with anti-TNF
7. Patients in clinical remission after six or twelve months will be tested for subclinical synovitis with a positron emission tomography (PET) scan, ultrasound and magnetic resonance imaging (MRI)
Tertiary outcome:
1. Bone and cartilage metabolism
2. Cardiovascular and endocrine parameters
Overall trial start date
01/03/2008
Overall trial end date
01/01/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Active RA according to American College of Rheumatology (ACR) criteria
2. Greater than six swollen joints or greater than six painful joints
3. Disease duration less than two years
4. Erythrocyte sedimentation rate (ESR) greater than 28 mm
5. Visual analogue scale (VAS) greater than 20
6. Age greater than 18 years, either sex
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
160
Participant exclusion criteria
1. Prior treatment DMARDs (except hydroxychloroquine)
2. Insulin-dependent diabetes mellitus
3. Uncontrollable non-insulin dependent diabetes mellitus
4. Heart failure New York Heart Association (NYHA) class 3 - 4
5. Uncontrollable hypertension
6. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) greater than three times normal values
7. Reduced renal function (serum creatinine greater than 15 mcmol)
8. Contra-indications for methotrexate, sulphasalazine or prednisolone
9. Indications of probable tuberculosis
Recruitment start date
01/03/2008
Recruitment end date
01/01/2012
Locations
Countries of recruitment
Netherlands
Trial participating centre
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Sponsor information
Organisation
Vrije University Medical Centre (VUMC) (The Netherlands)
Sponsor details
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
+31 (0)20 444 3432
www.secretariaatreumatologie@vumc.nl
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Top Institute Pharma (TIPharma) (The Netherlands)
Alternative name(s)
TI Pharma
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
Netherlands
Funder name
Wyeth Pharmaceuticals B.V. (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
Basic results (scientific)
Publication list
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/24818633
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27247434