Cardiovascular Diseases
Conditions
Keywords
Aspirin, Chronotherapy
Brief summary
This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime.
Detailed description
Aspirin is the cornerstone of preventive cardiovascular disease (CVD) treatment and bedtime intake of aspirin (chronotherapy) has been shown to reduce morning activity of platelets. It has been shown that platelet reactivity follows a clear circadian rhythm, with a peak of platelet reactivity during the morning (6-12 AM). Importantly, studies have shown in meta-analyses that high platelet activity is predictive of adverse cardiovascular outcomes in patients with stable CVD. Given this knowledge, it is highly likely that the morning peak of platelet reactivity contributes to the morning peak of cardiovascular events and that reduction of morning platelet activity prevents cardiovascular events during morning hours. This may be achieved by intake of aspirin at bedtime instead of on awakening. This study will be a comparative effectiveness research to determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after awakening and aspirin before bedtime.
Interventions
OTHERplacebo after awakening + aspirin before bedtime
determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after wakening and aspirin before bedtime.
OTHERaspirin after awakening + placebo before bedtime
determine the difference in major adverse cardiovascular events between the group with aspirin after awakening and placebo before bedtime and the group with placebo after wakening and aspirin before bedtime.
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
parallel double blinded placebo controlled randomized clinical trial design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Use of low-dose aspirin (acetylsalicylic acid 80mg \[brand name: acetylsalicylic acid cardio TEVA\]\ ) * Patients using aspirin from an MDD ('Baxter') * Capacity to give informed consent (IC)
Exclusion criteria
* Pregnancy * Mental or physical disability to fulfil study requirements * Insufficient knowledge of the Dutch language * Patients currently participating in another (clinical) trial or study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence rate of major adverse cardiovascular events | maximum of 4 years follow up | the difference in number of participants with a major adverse cardiovascular events, defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, transient ischemic attack, need for repeat revascularízation by redo-CABG or repeat percutaneous intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparing the incidence rate of major cardiovascular events between the two groups in the morning (6-12), evening (12-21) and night (21-6). | maximum of 4 years follow up | It is expected that bedtime aspirin reduces the number of participants with primary outcome (major cardiovascular events) more during morning hours (6-12h) compared with the rest of the day. So we will compare the mornig events, afternoon/evening and night events between the two groups and compare the difference. |
| Incidence rate of side-effects between the 2 groups | maximum of 4 years follow up | the difference between the 2 groups of the number of participants that experience side-effects (e.g. bleeding, gastrointestinal symptoms) |
| cost-effectiveness of the intervention | maximum of 4 years follow up | Comparing the relative costs and outcomes (effects) between the 2 groups. Data from questionnaire (use of health care) and data from the primary and secondary health care systems. We can compare the use of health care between the two groups en we can calculate the difference in cost between the two groups. So we can estimate if our intervention is cost-effective. |
Other
| Measure | Time frame | Description |
|---|---|---|
| difference in quality of life | maximum of 4 years follow up | Health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Rated level per dimensions can be coded as a number 1-5, which indicates having no problems for 1 and having extreme problems for 5. We can define 3,125 (=55) different health states. We compare the average health status of the groups at the beginning and at the end of the study. See if there is a difference in health status/ quaulity of life between the two groups. |
Countries
Netherlands
Outcome results
None listed