Condition category
Musculoskeletal Diseases
Date applied
14/03/2008
Date assigned
31/03/2008
Last edited
02/06/2016
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

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 measures

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

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

http://www.vumc.nl

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

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/24818633
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27247434

Publication citations

Additional files

Editorial Notes

01/06/2016: Publication reference added.