TIME ASPIRIN: Chronotherapy With Aspirin for Reduction of Cardiovascular Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Chronotherapy With Aspirin for Reduction of Cardiovascular Disease

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Other: placebo after awakening + aspirin before bedtime
* Other: aspirin after awakening + placebo before bedtime


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: parallel double blinded placebo controlled randomized clinical trial design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: aspirin after awakening + placebo before bedtime<br>Acetylsalicylic acid 80 mg once daily, orally. Intake in de morning after awakening. Participants already use acetylsalicylic acid 80 mg once daily due to secondary prevention of cardiovascular disease. Placebo tablet once daily will be added to their medication. The placebo tablet will be taken before bedtime, orally. The placebo is given throughout the study. | Other: aspirin after awakening + placebo before bedtime<br>* 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.<br>* Other names: Acetylsalicylic acid Cardio Teva 80 mg, intake after awakening;|
| Experimental: placebo after awakening +aspirin before bedtime<br>Acetylsalicylic acid 80 mg once daily, orally. The time will be changed form morning to bedtime. Participants already use acetylsalicylic acid 80 mg once daily due to secondary prevention of cardiovascular disease. Placebo tablet once daily will be added to their medication. The placebo tablet will be taken after awakening, orally. The placebo is given throughout the study. | Other: placebo after awakening + aspirin before bedtime<br>* 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.<br>* Other names: Acetylsalicylic acid Cardio Teva 80 mg, intake before bedtime;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of major adverse cardiovascular events | 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. | maximum of 4 years follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing the incidence rate of major cardiovascular events between the two groups in the morning (6-12), evening (12-21) and night (21-6). | 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. | maximum of 4 years follow up | 
| Incidence rate of side-effects between the 2 groups | the difference between the 2 groups of the number of participants that experience side-effects (e.g. bleeding, gastrointestinal symptoms) | maximum of 4 years follow up | 
| cost-effectiveness of the intervention | 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. | maximum of 4 years follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspirin, Chronotherapy