|- candidate number||8286|
|- NTR Number||NTR2443|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||2-aug-2010|
|- Secondary IDs||09-249 / 2009-015653-20 ; MEC AMC / EudraCT|
|- Public Title||Etanercept cohort studie.|
|- Scientific Title||Prospective study on the effects of etanercept treatment in patients with rheumatoid arthritis who are naÔve for TNF-alpha blocking therapy or are non-responders to prior treatment with other anti-TNF-alpha medication.|
|- ACRONYM||Etanercept cohort studie |
|- hypothesis||Previous randomised trials have shown the efficacy of etanercept in RA patients. In this study we will evaluate the respons of etanercept in anti-TNF naive patients compared to patients who have failed other anti-TNF. We will look for clinical parameters and serological markers that may differentiate responders from non-responders on etanercept.|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||1. Patients with the diagnosis rheumatoid arthritis according to the American Rheumatism Association (ARA) 1987 criteria and in ACR 1991 functional classes I, II, and III;|
2. The patient is naÔve for anti-TNF-alpha therapy or has failed other prior TNF-alpha blockers;
3. DAS 28 3.2;
4. Failure on two previously used DMARDs;
5. Age > 18 and =< 85 years old;
6. Use concurrent methotrexate treatment (5 - 30 mg/week; stable since at least 28 days before initiation) during the study. Subjects may be taking nonsteroidal anti-inflammatory drugs, provided the dose and frequency have been stable for at least 28 days. Subjects may be receiving prednisone therapy < 10 mg/day provided that the dosage has been stable for at least 28 days prior to entry.
|- Exclusion criteria||1. Pregnancy;|
3. A history of or current acute inflammatory joint disease of different origin e.g. mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiterís syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years;
4. Acute major trauma;
5. Therapy within the previous 60 days with:
A. Any experimental drug;
B. Alkylating agents, e.g. cyclophosphamide, chlorambucil;
D. Monoclonal antibodies (including infliximab and etanercept);
E. Growth factors;
F. Other cytokines.
6. Therapy within the previous 28 days with:
A. Parenteral or intraarticular corticoid injections;
B. Oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily;
C. Present use of DMARDs other than methotrexate.
7. Receipt of any live (attenuated) vaccines within 4 weeks prior to baseline;
8. Fever (orally measured > 38 įC), chronic infections or infections requiring anti-microbial therapy;
9. Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus;
10. Manifest cardiac failure (stage III or IV according to NYHA classification);
11. Progressive fatal disease/terminal illness;
12. A history of lymphoproliferative disease or treatment with total lymphoid irradiation;
13. A white cell count less than 3.5 x 109/l;
14. Platelet count less than 100 x 109/l;
15. Haemoglobin of less than 5.3 mmol/l;
16. Body weight of less than 45 kg;
17. History of drug or alcohol abuse;
18. Any concomitant medical condition which would in the investigatorís opinion compromise the patientís ability to tolerate, absorb, metabolize or excrete the study medication;
19. Inability to give informed consent;
20. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-jan-2010|
|- planned closingdate||31-dec-2015|
|- Target number of participants||200|
|- Interventions||Study medication and dosage:|
1. Etanercept EU/1*99/126/001;
2. Dosage: 50 mg by subcutaneous injection every week.
|- Primary outcome||The primary endpoint of the study is the percentage of patients with a moderate to good response to etanercept treatment at 16 weeks according to the Eular response criteria which is also applied in routine rheumatological practice. |
Furthermore the primary endpoint of the study is to search for clinical parameters and/or serological markers that possibly distinguish responders from non-responders to TNF-α blockade by etanercept.
|- Secondary outcome||The secundary endpoint of the study is the proportion of patients with a 20%, 50%, and 70% clinical improvement according to the ACR response criteria  at 4, 16, 28, 40 and 52 weeks after the initiation of etanercept treatment. The parameters of disease activity e.g. tender joint count, swollen joint count, patientís assessment of pain, patientís global assessment, investigators global assessment, duration of morning stiffness, health assessment questionnaire, DAS 28, SF-36 (short form health survey) and RADAI  will be assessed at each time point starting from baseline.
We will look for genetic markers, e.g. genetic polymorphisms in TNF-alpha genes, that may predict diagnosis, efficacy and side-effects of treatment in the individual patient.
In the future micro-array analysis may be done to screen for new markers that distinguish responders from non-responders.
|- Timepoints||Week 0, 4, 16, 28, 40 and 52.|
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. P.P. Tak|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. P.P. Tak|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Division of Clinical Immunology and Rheumatology|
(Source(s) of Monetary or Material Support)
|Academic Medical Center (AMC), Division of Clinical Immunology and Rheumatology|
|- Brief summary||A monocenter prospective, exploratory study with a 2 to 4-week screening period and a 52-week follow-up period in 200 RA patients who receive etanercept treatment in routine rheumatological practice and are TNF-alpha blockade naÔve or have failed to (or no longer) respond to other anti-TNF-alpha treatment. There is no group of patients receiving control treatment, since it is considered unethical to withhold active treatment for 52 weeks in patients with active RA.|
Recruitment in the Netherlands.
|- Main changes (audit trail)|
|- RECORD||2-aug-2010 - 19-dec-2012|