Condition category
Musculoskeletal Diseases
Date applied
05/03/2007
Date assigned
23/11/2007
Last edited
14/06/2011
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 Bruce Kirkham

ORCID ID

Contact details

Rheumatology Department
4th floor
Thomas Guy House
Guy's Hospital
London
SE1 9RT
United Kingdom
bruce.kirkham@gstt.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RJI 03/0139

Study information

Scientific title

Acronym

DIVERT - Defining Infliximab Vascular Effects Rheumatoid arthritis Trial

Study hypothesis

That surrogate measures of vascular disease (pulse wave velocity, flow mediated dilatation, carotid-intimal media thickness), will improve after infliximab therapy in patients with active rheumatoid arthritis.

Ethics approval

Guy's Hospital Research Ethics Committee, approved on 28 November 2003 (ref: RJI - 03/0139)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Rheumatoid Arthritis

Intervention

Placebo controlled 2:1 randomisation, active infliximab (3 mg/kg intravenous) vs placebo infusion for 26 weeks, then open label until week 56, with placebo escape arm at week 14.

Intervention type

Drug

Phase

Not Specified

Drug names

infliximab

Primary outcome measures

The following will be assessed at baseline (Week 0), Week 24 and Week 56, unless indicated otherwise:
1. Endothelial function (Flow Mediated Dilatation [FMD]). This will be assessed at Week 8 and Week 16 in addition to the timepoints stated above.
2. Vascular structure:
2.1. Pulse Wave Velocity [PWV]
2.2. Augmentation Index [Aix]
2.3. Carotid Intimal Medial Thickening [CIMT]

Secondary outcome measures

The following will be assessed at baseline (Week 0), Week 24 and Week 56, unless indicated otherwise:
1. RA disease activity:
1.1. Modified Health Assessment Questionnaire (HAQ). This will be assessed at Week 8 and Week 16 in addition to the timepoints stated above.
1.2. 28 swollen and tender joint counts. This will be assessed at Week 8 and Week 16 in addition to the timepoints stated above.
1.3. Erythrocyte Sedimentation Rate (ESR)
1.4. Patient Global Assessment (PGA) using a 100 mm visual 1.5. Analogue scale and Disease Activity Score 28 (DAS 28). This will be assessed at Week 8 and Week 16 in addition to the timepoints stated above.

2. CV risk factors:
2.1. Systolic and diastolic Blood Pressure (BP)
2.2. Body Mass Index (BMI)
2.3. High sensitivity C-Reactive Protein (HsCRP)
2.4. Serum fasting lipid profile (total cholesterol, High and Low Density Lipoprotein fractions [HDL, LDL] and triglycerides)
2.5. Oxidised LDL sub-fractions
2.6. Insulin resistance measured by log homeostasis model assessment (HOMA)
2.7. Serum levels of soluble Intracellular Adhesion Molecules (ICAM)
2.8. Vascular Cell Adhesion Molecules (VCAM) and adiponectin

Overall trial start date

15/05/2003

Overall trial end date

15/05/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. RA defined by American College of Rheumatology criteria
2. Referred for TNF-blocking therapy according to the British Society of Rheumatology (BSR) criteria
3. Patients giving written informed consent
4. Patients failed two DMARDs including methotrexate
5. Disease Activity Score 28 (DAS 28) greater than 5.1 on two occasions four weeks apart
6. Patients taking methotrexate (<=25 mg/week)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. Age <18 years
2. History of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus
3. Previous treatment with infliximab or any therapeutic agent targeted at reducing TNFa
4. Treatment with aspirin
5. Patients with evidence of current or previous infection with tuberculosis (TB)

Recruitment start date

15/05/2003

Recruitment end date

15/05/2005

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Rheumatology Department
London
SE1 9RT
United Kingdom

Sponsor information

Organisation

Guy's & St Thomas' NHS Foundation Trust (UK)

Sponsor details

R&D Department
Connybeare House
Guy's Hospital
St Thomas Street
London
SE1 9RT
United Kingdom
jackie.pullen@gstt.nhs.uk

Sponsor type

Government

Website

http://www.guysandstthomas.nhs.uk/

Funders

Funder type

Industry

Funder name

Centocor BV (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

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/18930987

Publication citations

  1. Results

    Wong M, Oakley SP, Young L, Jiang BY, Wierzbicki A, Panayi G, Chowienczyk P, Kirkham B, Infliximab improves vascular stiffness in patients with rheumatoid arthritis., Ann. Rheum. Dis., 2009, 68, 8, 1277-1284, doi: 10.1136/ard.2007.086157.

Additional files

Editorial Notes