Clinical trial NCT06856772: Randomized Comparison of Morning Versus Bedtime Administration of Statins: A Cardiovascular Circadian Chronotherapy (C3) Trial
Official title: Randomized Comparison of Morning Versus Bedtime Administration of Statins: A Cardiovascular Circadian Chronotherapy (C3) Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Cardiovascular Diseases (CVD)
Drug Effect
Atherosclerosis Cardiovascular Disease
Keywords: Statin
Circadian Rhythm
Randomized Controlled Trial
Pragmatic
Outcomes
Cardiovascular disease
Prevention
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Herlev and Gentofte Hospital
First posted: 2025-03-04
Enrollment: 42000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Statins inhibit hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase which catalyzes the rate-limiting step in cholesterol synthesis. This in turn leads to reductions in concentrations of low-density lipoprotein (LDL) cholesterol and C-reactive protein which reduces the risk of incident atherosclerotic events among individuals both with and without a history of atherosclerotic cardiovascular Several pilot studies have suggested potential benefits of taking statin in the evening rather than in the morning.

The primary objective of this study is to examine whether statin 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 statin.

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 statin treatment regardless of the presence or absence of established cardiovascular disease. Participants will be randomized 1:1 to either statin administration at bedtime or in the morning. The trial is event-driven.

Eligibility criteria: Inclusion Criteria:

* Age \>=18 years
* Current treatment with atorvastatin 10-80 mg, rosuvastatin 5-40 mg, simvastatin 10-80 mg or pravastatin 20-40 mg (as recorded in the Danish National Prescription Registry and confirmed by the participant via questionnaire)
* Signed informed consent

Exclusion Criteria:

* none

Primary outcomes:
measure: Composite of hospitalization for myocardial infarction, hospitalization for stroke or cardiovascular death
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
Secondary outcomes:
measure: Hospitalization for myocardial infarction
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Hospitalization for stroke
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Cardiovascular death
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: All-cause death
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
Other outcomes:
measure: Hospitalization for unstable angina
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Coronary revascularization
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Any arterial revascularization
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Any venous thromboembolism
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Hospitalization for heart failure
timeFrame: Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).
measure: Hospitalization for rhabdomyolysis
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Any incident cancer
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Any incident renal disorder
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Any incident hepatic disorder
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Bleeding episodes requiring hospitalization
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Any Incident Diabetes mellitus
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Plasma Lipid levels
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Plasma C-reactive protein level
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Time of day of hospitalization for myocardial infarction
timeFrame: From date of randomization until end of study (up til 5 years)
measure: Time of day of hospitalization for stroke
timeFrame: From date of randomization until end of study (up til 5 years)
Locations:
city: Hellerup
country: Denmark
facility: Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
Study officials:
References: