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van CCT (UK)

van CCT (UK)

Identification of predictive factors in synovial samples for the clinical response to TNF-alpha blockade in rheumatoid arthritis.

- candidate number2396
- NTR NumberNTR859
- Date ISRCTN created1-feb-2007
- date ISRCTN requested28-jan-2007
- Date Registered NTR8-jan-2007
- Secondary IDsN/A 
- Public TitleIdentification of predictive factors in synovial samples for the clinical response to TNF-alpha blockade in rheumatoid arthritis.
- Scientific TitleIdentification of predictive factors in synovial samples for the clinical response to TNF-alpha blockade in rheumatoid arthritis.
- hypothesisCan 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) studiedRheumatoid arthritis
- Inclusion criteria1. 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;
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 criteria1. 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, ReiteríŽs 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 receivedyes
- multicenter trialyes
- randomisedno
- group[default]
- Type2 or more arms, non-randomized
- Studytypeintervention
- planned startdate 1-apr-2001
- planned closingdate1-mei-2004
- Target number of participants143
- InterventionsInfliximab 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 outcome1. 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 outcomeSecondary immunohistologic outcome:
Analysis of the synovial cell infiltrate, and cytokines other than TNFalpha.
- TimepointsN/A
- Trial web siteN/A
- statusstopped: trial finished
- 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)
- PublicationsAnn Rheum Dis. 2007 Nov 29. [Epub ahead of print]
- Brief summaryA 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)
- RECORD8-jan-2007 - 12-jun-2008

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