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| [ Print-friendly version ] |
| 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 |
| ClinicalTrials.gov identifier | |
| Public 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 |
| Scientific title | |
| Acronym | COBRA-light |
| Serial number at source | 2007/150; NTR1213 |
| 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 | Ethics approval received from the METC VUmc-Amsterdam (The Netherlands) on the 6th September 2007 (ref: 2007/150). |
| Study design | An open randomised, active controlled, parallel group, multicentre trial |
| Countries of recruitment | The Netherlands |
| Disease/condition/study domain | Rheumatoid arthritis |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/03/2008 |
| Anticipated end date | 01/01/2012 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 160 |
| Interventions |
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. |
| Primary outcome measure(s) | Difference in delta DAS compared at baseline between the both treatment strategies after six months. |
| 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 |
| Sources of funding |
1. Top Institute Pharma (TIPharma) (The Netherlands)
2. Wyeth Pharmaceuticals B.V. (The Netherlands) |
| Trial website | |
| Publications | |
| Contact name | Mrs Debby den Uyl |
| Address | De Boelelaan 1117 |
| City/town | Amsterdam |
| Zip/Postcode | 1081 HV |
| Country | Netherlands |
| Tel | +31 (0)20 444 3981 |
| d.denuyl@vumc.nl | |
| Sponsor | Vrije University Medical Centre (VUMC) (The Netherlands) |
| Address | De Boelelaan 1117 |
| City/town | Amsterdam |
| Zip/Postcode | 1081 HV |
| Country | Netherlands |
| Tel | +31 (0)20 444 3432 |
| Fax | +31 (0)20 444 2138 |
| www.secretariaatreumatologie@vumc.nl | |
| Sponsor website: | http://www.vumc.nl |
| Date applied | 14/03/2008 |
| Last edited | 31/03/2008 |
| Date ISRCTN assigned | 31/03/2008 |
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