To study whether ticagrelor, added to acetylsalicylic acid, modulates the inflammatory response to the administration of lipopolysaccharide (LPS) in humans in vivo.
ID
Source
Brief title
Condition
- Other condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Health condition
inflammatie/immuunsysteem
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Area under the curve of various pro-inflammatory cytokines
Secondary outcome
platelet-monocyte complex formation and markers of platelet function; plasma
concentration of adenosine
Background summary
In patients suffering a myocardial infarction, the administration of P2Y12
receptor antagonists clearly improve prognosis. It appeared that both the
irreversible inhibitor prasugrel and the reversible inhibitors ticagrelor
improved cardiovascular mortality compared to clopidogrel. One of the
hypothesis that might explain the superiority of these compounds compared to
clopidogrel, is that they might affect the inflammatory response which occurs
in the setting of an acute myocardial infarction.
Study objective
To study whether ticagrelor, added to acetylsalicylic acid, modulates the
inflammatory response to the administration of lipopolysaccharide (LPS) in
humans in vivo.
Study design
Prospective randomized controlled-trial, according to a PROBE design
(prospective randomized open blinded-endpoint study).
Intervention
Participants will be randomized to receive either:
- acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) +
placebo (once daily)
- acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg)+
ticagrelor (90 mg twice daily for 7 days, after a loading dose of 180 mg)
- acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg)+
clopidogrel (75 mg once daily for 7 days, after a loading dose of 300 mg)
- placebo (twice daily
Study burden and risks
A physical examination, electrocardiography and blood sampling will be
performed in all participants. All subjects will be treated with ticagrelor (90
mg twice a day) or clopidogrel on top of acetylsalicylic acid or placebo.
Potential side effects of ticagrelor and the other P2Y12
inhibiotors/acetylsalicyclic acid include bleeding (epistaxis, skin haematomas,
gingival bleeding, gastro-intestinal bleeding, bleeding on puncture side).
Ticagrelor might also induce dyspnea. These risks however are limited due to
the short treatment period of 7 days and selection of healthy volunteers. There
is no direct benefit for the participants from this study.
Postbus 9101 147
Nijmegen 6500 HB
NL
Postbus 9101 147
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
- Age >= 18 and <= 35 years
- Male
- Healthy
Exclusion criteria
- History, signs or symptoms of cardiovascular disease
- History of chronic obstructive pulmonary disease (COPD) or asthma
- History of hemorrhagic diathesis, or any other disorder associated with increased risk of bleeding
- Previous spontaneous vagal collapse
- Use of any medication
- Smoking
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block, third degree atrioventricular block or a complex bundle branch block
- Hypertension (defined as RR systolic > 160 mmHg or RR diastolic > 90 mmHg)
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
- Renal impairment (defined as MDRD < 60 ml/min)
- Liver enzyme abnormalities ((defined as ALAT and/or ASAT > twice upper limit of normality)
- Thrombocytopenia (<150*109/ml) or anemia (haemoglobin < 8.0 mmol/L)
- Any obvious disease associated with immune deficiency
- Febrile illness in the week before the LPS challenge.
- Hypersensitivity to ticagrelor or any excipients
- Active pathological bleeding
- History of intracranial haemorrhage
- history of dyspepsia
- quantitative bleeding assessment tool (BAT) score > 3
- Participation in another drug trial or donation of blood 3 months prior to the planned LPS
challenge
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-005537-30-NL |
| CCMO | NL51923.091.14 |