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 |
| Secondary identifying numbers | 2007/150; NTR1213 |
- 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
Scientific
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
| Phone | +31 (0)20 444 3981 |
|---|---|
| d.denuyl@vumc.nl |
Study information
| Study design | Open randomised active-controlled parallel-group multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/03/2008 |
| Completion date | 01/01/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 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
1081 HV
Netherlands
Sponsor information
Vrije University Medical Centre (VUMC) (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
| Phone | +31 (0)20 444 3432 |
|---|---|
| www.secretariaatreumatologie@vumc.nl | |
| Website | http://www.vumc.nl |
"ROR" |
https://ror.org/00q6h8f30 |
Funders
Funder type
Industry
Top Institute Pharma (TIPharma) (The Netherlands)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- TI Pharma
- Location
- Netherlands
Wyeth Pharmaceuticals B.V. (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
Editorial Notes
21/09/2020: Publication reference added.
01/06/2016: Publication reference added.
