Condition category
Circulatory System
Date applied
12/11/2012
Date assigned
14/01/2013
Last edited
17/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Heart attacks are caused by blood clots which form in the heart arteries and obstruct blood flow. These occur as a result of both acute and chronic inflammation occurring within the blood vessel walls. Tumour necrosis factor alpha (TNF-alpha) is an inflammatory molecule that may be instrumental in the development of artery inflammation that leads to heart attacks. The main aim of the study was to work out if specific anti-inflammatory treatment, suppressing the effects of TNF-alpha might be beneficial following a heart attack.

Who can participate?
We at the Royal Infirmary in Edinburgh recruited patients who have suffered heart attacks but who are otherwise well.

What does the study involve?
On the first day, patients underwent a forearm study which was carried out in a side room located within the Cardiology ward. This was to assess how well blood vessels are able to appropriately relax. This consisted of lying on a bed for 3 hours in a warm room. Some bands were placed around both arms which would tighten up for short periods and from time to time. A very small needle was placed in the artery of one arm and two plastic tubes (cannulae) were placed into the veins, one in each arm. This part of the study is associated with some slight discomfort and we use local anaesthetic to minimise this. Small amount of drugs (substance P, acetylcholine and sodium nitroprusside) were administered and samples of blood (up to 200 ml on each occasion) were taken from the cannulae. The drug doses are very small and should only affect the arm. They can cause flushing and some mild swelling in the forearm. The effects are however self-limiting and of short duration. The blood samples were analysed for components in the blood that play a part in the clotting and inflammatory mechanisms. Immediately after this patients were assigned by chance (randomised) to receive either an infusion of Etanercept or a dummy infusion (saline) over 30 minutes. There is therefore a one in two chance you will not receive the study drug. On the second day (24 hours later) you will undergo a second and final forearm study.

What are the possible benefits and risks of participating?
Treatment with anti-TNF-α monoclonal antibodies may have beneficial effects. We do not anticipate that you will experience any side effects from this drug (etanercept) although an allergic reaction to this drug may rarely occur.

Where is the study run from?
Edinburgh Royal Infirmary (UK)

When is the study starting and how long is it expected to run for?
May 2003 to August 2009

Who is funding the study?
British Heart Foundation (UK)

Who is the main contact?
1. Dr Gareth J Padfield (gareth.padfield@nhs.net)
2. Prof David E Newby (d.e.newby@ed.ac.uk)

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Newby

ORCID ID

Contact details

British Heart Foundation Centre for Cardiovascular Science
University of Edinburgh
Chancellor’s Building
Edinburgh
EH16 4SU
United Kingdom
-
d.e.newby@ed.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2001/R/CAR/01

Study information

Scientific title

Cardiovascular effects of tumour necrosis factor alpha antagonism in patients with acute myocardial infarction: a first in man study

Acronym

Study hypothesis

Inflammation causes and destabilises atheroma. Circulating tumour necrosis factor - alpha (TNF-α) concentrations are increased in acute coronary syndromes and is expressed at higher concentrations in unstable atheromatous plaques. Treatment with anti-TNF-α monoclonal antibodies may have beneficial effects on vascular function (vasomotor and fibrinolytic function) and flow cytometric measures of platelet aggregation.

Ethics approval

Lothian research and ethics committee, April 2001, ref: LREC/2001/4/18

Study design

Double-blind parallel-group randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Acute myocardial infarction

Intervention

Patients presenting with acute myocardial infarction randomised to received an intravenous infusion of etanercept (10 mg) or saline placebo over 30 minutes.

Intervention type

Drug

Phase

Phase II

Drug names

Etanercept

Primary outcome measures

Platelet monocyte aggregation, peripheral vasomotor and fibrinolytic function at baseline and again 24 hours later

Secondary outcome measures

Leukocyte count and plasma cytokine concentrations at baseline and again 24 hours later

Overall trial start date

01/05/2003

Overall trial end date

01/08/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. A typical history of myocardial ischaemia lasting more than 20 minutes within 24 hours prior to admission
2. An elevated troponin I(>0.1µg/L) and/or electrocardiographic changes
3. Age ≥18 years of age, either sex
4. Screening full blood count (FBC) must meet the following criteria: healmoglobin (Hb) > 85g/L, white cell count (WCC) > 3.5 x 109/L, neutrophils > 1.5 x 109/L, platelets > 100 x 109/L
5. Subjects must be able to adhere to the study visit schedule and other protocol requirements
6. The subject must be capable of giving informed consent and the consent must be obtained prior to screening procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

26

Participant exclusion criteria

1. Women of child bearing potential
2. Systolic blood pressure >190mmHg or <100mmHg
3. Malignant arrhythmias
4. Renal or hepatic failure
5. Severe or significant co-morbidity
6. Previous history of blood dyscrasia
7. Unable to tolerate the supine position
8. Opportunistic infection within the previous 6 months, human immunodeficiency virus, serious infection within the previous 2 months, chronic/recurrent infection
9. A history of malignancy within the previous 5 years, lymphoproliferative disease, or multiple sclerosis/ other demyelinating disorder
10. Patients with diabetes mellitus (type 1 or insulin-dependent)
11. Patients with systemic inflammatory disorder
12. Use of any investigational drug within 1 month prior to screening or within five half-lives of investigational agent, whichever is longer
13. Treatment with any other therapeutic agent targeted at reducing TNF (e...g pentoxifylline, thalidomide, etanercept etc) within 3 months of screening
14. Known recent substance abuse (drugs or alcohol)
15. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period

Recruitment start date

01/05/2003

Recruitment end date

01/08/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Edinburgh
Edinburgh
EH16 4SU
United Kingdom

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
-
mvm@ed.ac.uk

Sponsor type

University/education

Website

http://www.ed.ac.uk/home

Funders

Funder type

Charity

Funder name

British Heart Foundation (UK)

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

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

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23574969

Publication citations

Additional files

Editorial Notes

17/05/2016: Publication reference added.