|- candidate number||1453|
|- NTR Number||NTR262|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||7-sep-2005|
|- Secondary IDs||1 |
|- Public Title||BeSt, BehandelStrategieŽn in ReumatoÔde Artritis.|
|- Scientific Title||Treatment Strategies in Rheumatoid Arthritis: a randomized clinical trial to test the effectiveness of different treatment strategies in patients with early rheumatoid arthritis.|
|- hypothesis||There is a clinically and statistically significant difference in functional ability and progression of radiological joint damage after two years of follow-up in patients with early RA who receive initial combination therapy, combination therapy after failure of optimal treatment with MTX, or initial therapy with a TNFa-blocking agent, compared to those receiving combination therapy after intensive treatment with the most effective consecutive single DMARDs.|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||Patients (18 years or older) with rheumatoid arthritis (ACR 1987 criteria), diagnosis since less than 2 years, previously untreated with DMARDs, with active disease (at least 6/66 swollen and at least 6/68 painfull joints, and either ESR 28 mm or more or VAS general wellbeing (by patient) of 20 mm or more).|
|- Exclusion criteria||1. Previous therapy with DMARDs except for hydroxychloroquine; |
2. Pregnancy or wish to become pregnant during the study, or childbearing potential without adequate contraception;
3. Concomitant treatment with another experimental drug;
4. History or presence of malignancy within the last five years;
5. Bone marrow hypoplasia;
6. elevated hepatic enzyme levels (ASAT, ALAT >3 times normal value);
7. Serum creatinine level > 150 umol/l or estimated creatinine clearance of < 75ml/min;
8. Diabetes mellitus;
9. Alcohol or drug abuse.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mrt-2000|
|- planned closingdate||1-aug-2004|
|- Target number of participants||508|
|- Interventions||Treatment or RA with established antirheumatic medication according to 4 different, accepted strategies. |
Treatment adjustments made on the basis of threemonthly measurements of DAS (or on occurrence of side effects).
All patients are treated aggressively, aiming at low disease activity, based on threemonthly calculations of a Disease Activity Score (DAS).
In all four strategy groups the medication is increased or altered if the DAS is 2.4 or higher, or, if the DAS is less than 2.4 for at least 6 months, tapered to a single drug maintainance dose.
All medication steps are dictated by a strategy specific pharmacoprotocol.
The DAS is calculated by a trained research nurse who remains blinded for the treatment that patients receive.
|- Primary outcome||After 2 years of follow-up: functional ability as measured by HAQ (collected by blinded research nurse) and joint damage on X-rays of hands and feet (Sharp/van der Heijde method, random in time, by 2 independent physicians, X-rays masked for center and patient identity).|
|- Secondary outcome||1. Side effects;|
2. Quality of life;
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||MD. C.F. Allaart|
|- CONTACT for SCIENTIFIC QUERIES||MD. C.F. Allaart|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|Schering-Plough, Dutch Health Care Insurance Board (CVZ, independent governement organisation), Centocor BV Leiden|
|- Publications||1. Arthritis Rheum. 2005 Nov;52(11):3381-90. |
2. Clin Exp Rheumatol. 2006 Nov-Dec;24(6 Suppl 43):S-77-82.
3. Ann Intern Med. 2007 Mar 20;146(6):406-15.
4. Ann Rheum Dis. 2007 Sep;66(9):1227-32. Epub 2007 Apr 3.
5. J Rheumatol Suppl. 2007 Nov;80:25-33.
6. Arthritis Rheum. 2008 Feb;58(2 Suppl):S126-35.
7. Arthritis Rheum. 2008 May;58(5):1293-8.
|- Brief summary||Initial treatment with a combination of antirheumatic drugs including either a tapered high dose of prednisone or infliximab, results in earlier and better improvement in functional ability and in statistically significant less progression in joint damage, and not more side effects than initial treatment with monotherapy (either switching to or adding other medication if DAS remains to high). |
After 2 years, functional ability in all groups is comparable. This required multiple changes in treatment in the patients in the initial monotherapy groups, whereas many patients in the initial combination groups had been able to taper medication to a single drug maintainance dose. Overall, 42% of all patients reached clinical remission.
|- Main changes (audit trail)|
|- RECORD||8-sep-2005 - 16-jun-2008|