Condition category
Musculoskeletal Diseases
Date applied
07/04/2008
Date assigned
09/05/2008
Last edited
02/02/2015
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

Prof Jill Belch

ORCID ID

Contact details

Vascular and Inflammatory Diseases Research Unit
The Institute of Cardiovascular Research
University Division of Medicine and Therapeutics
Ninewells Hospital and Medical School
University of Dundee
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 632457
j.j.f.belch@dundee.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

ETADA90 v1

Study information

Scientific title

Effect of anti-tumour necrosis factor alpha (TNFα) therapy on endothelial function and other surrogate markers of cardiovascular disease in patients with rheumatoid arthritis

Acronym

Study hypothesis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by a symmetrical erosive polyarthritis with inflammatory multisystemic involvement. Most patients exhibit a chronic fluctuating course of disease that, if left untreated, results in progressive joint destruction, deformity, and disability. The patient with RA has their life span shortened by 15-20%, with 34-40% of excess deaths being due to cardiovascular disease.

Study aim:
To assess the effect of the TNFa blocking drug etanercept and adalimumab on endothelial dysfunction and other surrogate markers of cardiovascular diseases in patients with RA. We hypothesised that the biologic drugs have the potential to improve endothelial dysfunction and other surrogate markers of cardiovascular disease (CVD) in patients with RA. We believe that if etanercept and adalimumab can improve endothelial dysfunction in RA patients they may be able to reduce the cardiovascular morbidity and mortality seen in this group of patients.

Ethics approval

Tayside Committee on Medical Research Ethics. Date of approval: 05/09/2005 (ref: 05/S1401/112)

Study design

Observational open-label single-centre study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Rheumatoid arthritis

Intervention

This is an observational study. The drugs are prescribed by the rheumatology team, and this study assesses the impact of those drugs on blood vessel health.

90 RA patients (30 due to be started on methotrexate, 30 due to be started on etanercept and 30 due to be started on adalimumab) will be recruited from rheumatology clinics throughout Tayside. Treatment allocation (etanercept, adalimumab or methotrexate) will be decided by the rheumatologists in the clinic.

The drugs are normally prescribed as:
Etanercept: Subcutaneous injections 25 mg twice a week or 50 mg once a week
Adalimumab: Subcutaneous injections 40 mg every other week
Methotrexate: Orally once a week. Doses range from 7.5 mg a week to 25 mg a week

Surrogate markers of cardiovascular disease will be measured at baseline (before commencement of methotrexate/ etanercept/ adalimumab), 2 months and at 4 months.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Endothelial function measured by the following at baseline, 2 and 4 months:
1. Laser Doppler flowmetry after iontophoretic delivery of acetylcholine and sodium nitroprusside (microvascular)
2. Brachial artery flow mediated dilatation (macrovascular)

Secondary outcome measures

The following were assessed at baseline, 2 and 4 months:
1. Endothelial function measured by blood testing of vascular function and damage (E selectin,
thrombomodulin)
2. Arterial stiffness measured by ultrasound echo tracking and applanation tonometry
3. Oxidative stress (Isoprostane levels)
4. RA disease activity (28-item Disease Activity Score [DAS28], Health Assessment Questionnaire [HAQ], 36-item Short Form health survey [SF-36])

Overall trial start date

10/02/2006

Overall trial end date

25/04/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Both males and females, 18 years old or over
2. Fulfil the 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis
3. No exposure to anti-TNFa drugs in the last 3 months
4. Fulfil the National Institute for Clinical Excellence guidelines on the use of anti-TNFa drugs in rheumatoid arthritis* and be:
4.1. About to start etanercept or adalimumab (treatment group)
4.2. About to start methotrexate (control group)

* The patients in the control group must have had adequate therapeutic trial of at least one previous Disease Modifying Anti-Rheumatic Drug (DMARD) rather than two

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

90

Participant exclusion criteria

1. Previous cardiovascular or cerebrovascular event in the last 3 years
2. Undergoing treatment for a cardiovascular risk factor except:
2.1. Patients with hypertension on stable medication for the last 3 months
2.2. Patients with hypercholesterolaemia on stable medication for the last 3 months

Recruitment start date

10/02/2006

Recruitment end date

25/04/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Vascular and Inflammatory Diseases Research Unit
Dundee
DD1 9SY
United Kingdom

Sponsor information

Organisation

University of Dundee (UK)

Sponsor details

Research and Innovation Services
Dundee
DD1 4HN
United Kingdom
+44 (0)1382 344664
j.z.houston@dundee.ac.uk

Sponsor type

University/education

Website

http://www.dundee.ac.uk

Funders

Funder type

Industry

Funder name

Wyeth

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

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

2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20080919

Publication citations

Additional files

Editorial Notes