Condition category
Musculoskeletal Diseases
Date applied
01/02/2007
Date assigned
01/02/2007
Last edited
01/08/2011
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

Dr C A Wijbrandts

ORCID ID

Contact details

Academic Medical Center (AMC)
Department of Medicine
Division of Clinical Immunology and Rheumatology
F4-218
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 2171
c.a.wijbrandts@amc.uva.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

Study hypothesis

Can predictors of reponse to anti-Tumour Necrosis Factor (TNF) therapy be identified by immunohistochemical analysis of synovial tissue obtained before initiation of treatment?

Ethics approval

Approval received from the Medical ethical committee of the Academic Medical Center/University of Amsterdam on the 14th February 2001 (ref: MEC 01/003).

Study design

Multicentre phase IV prospective study

Primary study design

Interventional

Secondary study design

Multi-centre

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Rheumatoid arthritis

Intervention

Infliximab therapy (3 mg/kg intravenous [i.v.]) at week zero, two, six, 14 and every eight weeks.

Clinical efficacy assessments are performed at baseline and subsequently every four weeks up to week 24. Serum samples are drawn on these visits. At baseline synovial biopsies are obtained from a maximally inflamed joint.

Intervention type

Drug

Phase

Phase IV

Drug names

Infliximab

Primary outcome measures

1. Primary immunohistological outcome: TNF-alpha expression in synovial tissue as shown by immunohistochemistry and quantified by digital image analysis
2. Primary clinical outcome: clinical response at week 16 assessed using the DAS 28

Secondary outcome measures

Secondary immunohistological outcome: analysis of the synovial cell infiltrate, and cytokines other than TNFalpha.

Overall trial start date

01/04/2001

Overall trial end date

01/05/2004

Reason abandoned

Eligibility

Participant inclusion criteria

1. Men/women suffering from rheumatoid arthritis, based on the American Rheumatism Association (ARA) 1987 criteria, who failed at least one Disease Modifying Anti-Rheumatic Drug (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. Disease Activity Score (DAS 28) more than 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. more than 18 years of age and less than or equal to 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 of less than or equal to 10 mg/day provided that the dosage has been stable for at least two months prior to entry

Participant type

Patient

Age group

Not Specified

Gender

Both

Target number of participants

143

Participant 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 fusion protein
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 intra-articular 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 as more than 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 New York Heart Association [NYHA] classification)
13. Progressive fatal disease/terminal illness
14. Impaired coagulation
15. A congenital or acquired (known Human Immunodeficiency Virus [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), or a haematopoietic disease
16. A white cell count less than 3.5 x 10^9/l
17. Platelet count less than 100 x 10^9/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, metabolise 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

Recruitment start date

01/04/2001

Recruitment end date

01/05/2004

Locations

Countries of recruitment

Netherlands

Trial participating centre

Academic Medical Center (AMC)
Amsterdam
1100 DD
Netherlands

Sponsor information

Organisation

Academic Medical Centre (AMC) (The Netherlands)

Sponsor details

Division of Clinical Immunology and Rheumatology
P.O. Box 22660
Amsterdam
1100 DD
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.amc.uva.nl/

Funders

Funder type

Research organisation

Funder name

Dutch Arthritis Association (Reumafonds) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Netherlands Organisation for Health Research and Development (ZonMw) (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

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21279992
2. 2011 exploratory study results in http://www.ncbi.nlm.nih.gov/pubmed/21454308

Publication citations

  1. Results

    Klaasen R, Wijbrandts CA, Gerlag DM, Tak PP, Body mass index and clinical response to infliximab in rheumatoid arthritis., Arthritis Rheum., 2011, 63, 2, 359-364, doi: 10.1002/art.30136.

  2. Exploratory study results

    Klaasen R, Cantaert T, Wijbrandts CA, Teitsma C, Gerlag DM, Out TA, de Nooijer MJ, Baeten D, Tak PP, The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study., Rheumatology (Oxford), 2011, 50, 8, 1487-1493, doi: 10.1093/rheumatology/ker010.

Additional files

Editorial Notes