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

ISRCTN	ISRCTN55552928
DOI	https://doi.org/10.1186/ISRCTN55552928
Protocol serial number	2007/150; NTR1213
Sponsor	Vrije University Medical Centre (VUMC) (The Netherlands)
Funders	Top Institute Pharma (TIPharma) (The Netherlands), Wyeth Pharmaceuticals B.V. (The Netherlands)

Submission date: 14/03/2008
Registration date: 31/03/2008
Last edited: 21/09/2020

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

Mrs Debby den Uyl
Scientific

De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Phone	+31 (0)20 444 3981
Email	d.denuyl@vumc.nl

Study information

Primary study design	Interventional
Study design	Open randomised active-controlled parallel-group multicentre trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study acronym	COBRA-light
Study objectives	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(s)	METC VUmc-Amsterdam (The Netherlands), 06/09/2007, ref: 2007/150
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Methotrexate, sulphasalazine, prednisolone
Primary outcome measure(s)	Difference in delta DAS compared at baseline between the both treatment strategies after six months.
Key secondary outcome measure(s)	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
Completion date	01/01/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	160
Key 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
Key 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
Date of first enrolment	01/03/2008
Date of final enrolment	01/01/2012

Locations

Countries of recruitment

Netherlands

Study participating centre

De Boelelaan 1117

Amsterdam
1081 HV
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2015		Yes	No
Results article	results	01/09/2016		Yes	No
Results article	results	02/03/2021	21/09/2020	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

21/09/2020: Publication reference added.
01/06/2016: Publication reference added.