Randomized Comparison of Morning Versus Bedtime Administration of Aspirin: A Cardiovascular Circadian Chronotherapy (C3) Trial

Study Overview
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Brief Summary
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Wide variability in the antiplatelet effects of aspirin may lead to recurrent thromboembolic events. Several pilot studies have suggested potential benefits of taking aspirin at bedtime rather than in the morning. The primary objective of this study is to examine whether aspirin administration at bedtime versus in the morning provides a superior reduction in the incidence of major adverse cardiovascular events among patients with or without established atherosclerotic cardiovascular disease, who are already taking aspirin.

Detailed Description
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The study is a pragmatic, registry-based, open-label, randomized controlled trial combining the utilization of the Danish nationwide health registries and the official Danish electronic letter system (Digital Post/eBoks) into an innovative, decentralized trial requiring no study visits from participants. The nationwide health registries will be used for identification of potential participants and data collection, including baseline information and follow-up data, while the electronic letter system will be used for sending recruitment letters and communicating with participants. Study participants will provide electronic informed consent from home before inclusion and randomization. The trial will include patients currently in aspirin treatment regardless of the presence or absence of established cardiovascular disease. Participants will be randomized 1:1 to either aspirin administration at bedtime or in the morning. The trial is event-driven.

Official Title
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Randomized Comparison of Morning Versus Bedtime Administration of Aspirin: A Cardiovascular Circadian Chronotherapy (C3) Trial

Conditions
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Atherosclerosis, Cardiovascular Diseases, Drug Effect

Intervention / Treatment
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* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years Current chronic treatment with aspirin (as recorded in the Danish National Prescription Registry and confirmed by the participant via questionnaire) Signed informed consent Exclusion Criteria: There are no exclusion criteria for this trial

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin at bedtime<br>Participants randomized to aspirin administration at bedtime will be instructed to take their aspirin at approx. 8PM-12AM. | Drug: Aspirin<br>* Aspirin at currently prescribed dose<br>|
| Active Comparator: Aspirin in the morning<br>Participants randomized to aspirin administration in the morning will be instructed to take their aspirin upon awakening or with their breakfast (approx. 6-10AM). | Drug: Aspirin<br>* Aspirin at currently prescribed dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of hospitalization for myocardial infarction, hospitalization for stroke, coronary revascularization, or cardiovascular death |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization for myocardial infarction |  | Up to 3 years | 
| Hospitalization for stroke |  | Up to 3 years | 
| Coronary revascularization |  | Up to 3 years | 
| Cardiovascular death |  | Up to 3 years | 
| All-cause death |  | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspirin, Cardiovascular Disease, Prevention, Circadian Rhythm, Randomized Controlled Trial, Pragmatic, Outcomes