| - candidate number | 2396 |
| - NTR Number | NTR859 |
| - ISRCTN | ISRCTN36847425 |
| - Date ISRCTN created | 1-feb-2007 |
| - date ISRCTN requested | 28-jan-2007 |
| - Date Registered NTR | 8-jan-2007 |
| - Secondary IDs | N/A |
| - Public Title | Identification of predictive factors in synovial samples for the clinical response to TNF-alpha blockade in rheumatoid arthritis. |
| - Scientific Title | Identification of predictive factors in synovial samples for the clinical response to TNF-alpha blockade in rheumatoid arthritis. |
| - ACRONYM | N/A |
| - hypothesis | Can predictors of reponse to anti-TNF therapy be identified by immunohistochemical analysis of synovial tissue obtained before initiation of treatment? |
| - Healt Condition(s) or Problem(s) studied | Rheumatoid arthritis |
| - Inclusion criteria | 1. Men/women suffering from rheumatoid arthritis, based on the American Rheumatism Association (ARA) 1987 criteria, who failed at least one DMARD including methotrexate will be included in the study; 2. Patients in ARA functional classes I, II, and III may be included; 3. In addition the patients must fulfill the following criteria at baseline: a. DAS 28 >3.2; b. Patients global evaluation of his/her rheumatoid condition assessed as fair, poor or very poor; and investigators global evaluation of patients rheumatoid condition assessed as fair, poor or very poor; c. Be > 18 years of age and <= 85 years; d. 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 2 months prior to entry. |
| - Exclusion criteria | 1. Pregnancy; 2. Breastfeeding; 3. A history of or acute inflammatory joint disease of different origin e.g. mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter¡¦s syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years; 4. Acute major trauma; 5. Previous therapy at any time with: TNF-alpha directed monoclonal antibodies or p75 TNF receptor fusionprotein; 6. Therapy within the previous 60 days with: a. Any experimental drug; b. Alkylating agents, e.g. cyclophosphamide, chlorambucil; c. Antimetabolites; d. Monoclonal antibodies; e. Growth factors; f. Other cytokines; 7. 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; 8. A history of hypersensitivity to the study medication or to drugs with similar chemical structure; 9. Fever (orally measured > 38 °C), chronic infections or infections requiring anti-microbial therapy; 10. Known positive reaction to hepatitis B surface antigen; 11. Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus; 12. Manifest cardiac failure (stage III or IV according to NYHA classification); 13. Progressive fatal disease/terminal illness; 14. Impaired coagulation; 15. A congenital or acquired (known HIV-positive status) immunodeficiency, a history of cancer or lymphoproliferative disease or treatment with total lymphoid irradiation. (The known HIV-positive status may be defined either by a positive blood test or clinical diagnosis.) a haematopoietic disease; 16. A white cell count less than 3.5 x 109/l; 17. Platelet count less than 100 x 109/l; 18. Haemoglobin of less than 5.3 mmol/l; 19. Body weight of less than 45 kg; 20. History of drug or alcohol abuse; 21. Any concomitant medical condition which would in the investigators opinion compromise the patients ability to tolerate, absorb, metabolize or excrete the study medication; 22. Inability to give informed consent; 23. 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 | yes |
| - randomised | no |
| - group | [default] |
| - Type | 2 or more arms, non-randomized |
| - Studytype | intervention |
| - planned startdate | 1-apr-2001 |
| - planned closingdate | 1-mei-2004 |
| - Target number of participants | 143 |
| - Interventions | Infliximab therapy (3mg/kg i.v.) at week 0, 2, 6, 14 and every 8 weeks. Clinical efficacy assessments are performed at baseline and subsequently every 4 weeks up to week 24. Serum samples are drawn on these visits. At baseline synovial biopsies are obtained from a maximally inflamed joint. |
| - Primary outcome | 1. Primary immunohistologic outcome: TNF-alpha expression in synovial tissue as shown by immunohistochemistry and quantified by digital image analysis; 2. Primairy clinical outcome: Clinical response at week 16 assessed using the DAS28. |
| - Secondary outcome | Secondary immunohistologic outcome: Analysis of the synovial cell infiltrate, and cytokines other than TNFalpha. |
| - Timepoints | N/A |
| - Trial web site | N/A |
| - status | stopped: trial finished |
| - CONTACT FOR PUBLIC QUERIES | C.A. Wijbrandts |
| - CONTACT for SCIENTIFIC QUERIES | Prof. Dr. P.P. Tak |
| - Sponsor/Initiator | Academic Medical Center (AMC), Division of Clinical Immunology and Rheumatology |
| - Funding (Source(s) of Monetary or Material Support) | ZON-MW, The Netherlands Organization for Health Research and Development, Dutch Arthritis Association (Reumafonds) |
| - Publications | Ann Rheum Dis. 2007 Nov 29. [Epub ahead of print] |
| - Brief summary | A multicenter fase IV prospective study in patients with rheumatoid artrhitis investigating potential predictors of response to anti-TNF therapy. Synovial biopsies obtained pre-treatment were studied by immunohistochemistry to identify such predictors. All patients received active treatment with infliximab according to the normal regimen. Clinical response was assessed every 4 weeks from baseline up to week 24. |
| - Main changes (audit trail) | |
| - RECORD | 8-jan-2007 - 12-jun-2008 |
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