Plain English Summary
Background and study aims (to set the scene)
Despite many improvements in the treatment of heart disease and stroke, these conditions remain very common in Western countries, including the UK. One of the main treatments that is used to prevent heart attacks and strokes, in people who are at risk of these, including patients who have previously suffered heart disease or strokes, is aspirin. Aspirin works by inhibiting the activity of certain blood cells, called platelets, which play a role in forming clots in the arteries. However, despite taking aspirin, a number of patients who have previously had heart attacks or strokes experience another such event. These patients have been labelled as ‘aspirin resistant’, and much research is currently going on to try and find out why aspirin resistance occurs. Recently, several lines of evidence suggest that aspirin resistance may in fact be genetically determined, at least in part, although the genes concerned are presently not clear. This study aims to determine, both in healthy people and in patients with a history of heart disease or stroke, whether variations in certain genes that can affect the functioning of blood platelets may indeed give rise to aspirin resistance.
Who can participate?
Healthy adults aged at least 18.
What does the study involve?
Participants attend the study centre and, after a period of lying down resting, are asked to give a 100 ml blood sample (the equivalent of about 6 tablespoonfuls) from a vein. These samples are used for routine blood tests, to measure the functioning of the blood platelets in the laboratory and to study the DNA (genetic material) of some of the genes that may be important in controlling how platelets respond to aspirin. Participants are also be asked to give a urine sample at this visit, which is analysed to give another measure of how activated platelets are in the bloodstream. Some of the blood is frozen, for subsequent genetic analysis. Subjects are given aspirin 300mg daily for 4 weeks, at the end of which time they re−attend once again under the same conditions as above, for further blood (80 ml blood) and urine testing.
What are the possible benefits and risks of participating?
There are no specific benefit to taking part in the study, and participants treatment will not be affected in any way either by their participation / non-participation or by the results that obtained from them. However, the information that is obtained from this study may help to to treat future patients with (or at risk of) heart disease or stroke better. Participants may experience slight discomfort in the arm following insertion of a needle for taking blood. Aspirin treatment may give rise to bleeding or bruising, both at the site of blood taking and elsewhere, because aspirin works by thinning the blood slightly. Any such bruising or bleeding is usually minor, but may be more severe if the participant has a reason to bleed easily, for example recent surgery or a blood clotting disorder. Overall, the risk of increased bruising and bleeding (minor and major combined) is approximately 1 in 100. Additionally, aspirin can cause stomach irritation or even ulcers; however, participants who have a history of this will be excluded to minimize the risk of this happening.
Where is the study run from?
King's College London
When is the study starting and how long is it expected to run for?
January 2007 to December 2008
Who is funding the study?
Biotechnology and Biological Science Research Council
Who is the main contact?
Professor Albert Ferro
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
4069
Study information
Scientific title
An investigation into the genes underlying the clinical syndrome of aspirin resistance: a non-randomised interventional treatment trial
Acronym
Study hypothesis
1. What is the prevalence of true aspirin resistance in a healthy population?
2. Can a genetic basis be identified for this?
Ethics approval
Riverside Research Ethics Committee approved in February 2007, ref: 07/Q0401/1
Study design
Non-randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Non randomised study
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
Topic: Cardiovascular; Subtopic: Cardiovascular (all Subtopics); Disease: Cardiovascular
Intervention
As of 01/08/2016:
Subjects will attend clinic following an overnight fast, and having abstained from tobacco, caffeine−containing drinks and alcohol for at least 12 hours. 100 ml blood will be taken from an antecubital
vein using a 19G needle, for both genotyping and platelet phenotyping. These baseline bloods will also be sent for routine haematology and biochemistry screening (full blood count, renal function, liver profile, lipid profile, glucose, HbA1c, homocysteine, hsCRP). A urine sample will also be taken for measurement of 11−dehydrothromboxane B2 and creatinine (the ratio of 11−dehydrothromboxane B2 to creatinine in urine is a well validated index of platelet activation). One week later, subjects will re−attend under the same conditions as above, for further venesection (80 ml blood) and repeat platelet phenotyping (we will not need to repeat the DNA analyses, haematology or biochemistry testing on visit 2), in order to establish a stable baseline for platelet function studies. Another urine sample will be taken for measurement of 11−dehydrothromboxane B2 to creatinine ratio. Subjects will then be given aspirin 300mg daily for 4 weeks, at the end of which time they will re−attend once again under the same conditions as above, for further venesection (80 ml blood) and repeat platelet phenotyping and urinary 11−dehydrothromboxane B2 to creatinine ratio measurement.
Initial:
Aspirin 300 mg daily adminstered for 1 month. Follow up length: 1 month.
Intervention type
Drug
Phase
Phase IV
Drug names
Aspirin
Primary outcome measure
Presence of aspirin resistance at 1 month
Secondary outcome measures
Presence/absence of genetic polymorphisms in a number of candidate genes possibly related to aspirin at 1 month
Overall trial start date
01/01/2007
Overall trial end date
31/12/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Male or female aged 18 or more
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
Planned Sample Size: 100
Participant exclusion criteria
1. Significant co-morbidity
2. Current regular therapy with any drug
3. Ingestion of aspirin, other non-steroidal anti-inflammatory drug, or other anti-platelet agent within the previous 30 days
4. Previous reaction to aspirin or other anti-platelet drug
5. History of dyspepsia or peptic ulceration
6. Pregnancy or female currently trying to conceive. Females of reproductive age wishing to take part will be asked to undergo a pregnancy test prior to inclusion, and will participate only if the test is negative.
Recruitment start date
01/01/2007
Recruitment end date
31/12/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
King's College London
London
SE1 9NH
United Kingdom
Sponsor information
Organisation
Kings College London (UK)
Sponsor details
c/o Keith Brennan
1.8 Hodgkin Building
Guy's Campus
London
SE1 1UL
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Research council
Funder name
Biotechnology and Biological Science Research Council (BBSRC) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Heart Research UK (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
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
Basic results (scientific)
Publication list
2014 results: http://www.ncbi.nlm.nih.gov/pubmed/25099258