A placebo-controlled trial of anti-TNFa chimeric monoclonal antibody (infliximab, remicade) in the modification of vascular disease markers in active rheumatoid arthritis

ISRCTN	ISRCTN29665463
DOI	https://doi.org/10.1186/ISRCTN29665463
Protocol serial number	RJI 03/0139
Sponsor	Guy's & St Thomas' NHS Foundation Trust (UK)
Funder	Centocor BV (The Netherlands)

Submission date: 05/03/2007
Registration date: 23/11/2007
Last edited: 14/06/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Bruce Kirkham
Scientific

Rheumatology Department
4th floor
Thomas Guy House
Guy's Hospital
London
SE1 9RT
United Kingdom

Email	bruce.kirkham@gstt.nhs.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	DIVERT - Defining Infliximab Vascular Effects Rheumatoid arthritis Trial
Study objectives	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(s)	Guy's Hospital Research Ethics Committee, approved on 28 November 2003 (ref: RJI - 03/0139)
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	infliximab
Primary outcome measure(s)	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]
Key secondary outcome measure(s)	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
Completion date	15/05/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	30
Key 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)
Key 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)
Date of first enrolment	15/05/2003
Date of final enrolment	15/05/2005

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Rheumatology Department

London
SE1 9RT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2009		Yes	No