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

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Atherosclerosis; Drug Effect
• Intervention / Treatment: Drug: Aspirin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 32706
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Niklas Dyrby Johansen, MD; Phone Number: +4520204794; Email: niklas.dyrby.johansen@regionh.dk
• Study Contact Backup: Name: Manan Pareek, MD, PhD; Phone Number: +4525536900; Email: mananpareek@dadlnet.dk

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Recruiting
    • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
    • Contact: Niklas Dyrby Johansen, MD; Phone Number: +4520204794; Email: niklas.dyrby.johansen@regionh.dk
    • Contact: Manan Pareek, MD, PhD; Phone Number: +4525536900; Email: mananpareek@dadlnet.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin at bedtime; Participants randomized to aspirin administration at bedtime will be instructed to take their aspirin at approx. 8PM-12AM.	Drug: Aspirin; Aspirin at currently prescribed dose
Active Comparator: Aspirin in the morning; 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; Aspirin at currently prescribed dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
All-cause death	Up to 3 years
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

Other Outcome Measures

Outcome Measure	Time Frame
Bleeding episode requiring hospitalization	Up to 3 years
Hospitalization for intracranial hemorrhage	Up to 3 years
Hospitalization for gastrointestinal hemorrhage	Up to 3 years
Hospitalization for unstable angina	Up to 3 years
Any arterial revascularization	Up to 3 years
Any venous thromboembolism	Up to 3 years
Time of day of hospitalization for myocardial infarction	Up to 3 years
Time of day of hospitalization for stroke	Up to 3 years

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Investigators: Principal Investigator: Manan Pareek, MD, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: July 5, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Aspirin; Cardiovascular Disease; Prevention; Randomized Controlled Trial; Outcomes; Circadian Rhythm; Pragmatic
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: ASPIRIN-C3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Baseline and endpoint data will be collected from Danish administrative health registries, which are subject to Danish legislation and can only be made available to a third party under certain conditions. Please contact the sponsor in case of any inquiries.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No