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

NCT06856772 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: STATIN-C3
• Study Type: interventional
• Target: 42,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Diseases (CVD); Drug Effect; Atherosclerosis Cardiovascular Disease

Keywords

Statin; Circadian Rhythm; Randomized Controlled Trial; Pragmatic; Outcomes; Cardiovascular disease; Prevention

Outcome Measures

Primary Outcomes (1)

• Composite of hospitalization for myocardial infarction, hospitalization for stroke or cardiovascular death

  For Hospitalizations: Inpatient, at least 1 night

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

Secondary Outcomes (4)

• Hospitalization for myocardial infarction

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

• Hospitalization for stroke

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

• Cardiovascular death

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

• All-cause death

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

Other Outcomes (15)

• Hospitalization for unstable angina

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

• Coronary revascularization

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

• Any arterial revascularization

  Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years).

Study Arms (2)

Statin at bedtime

EXPERIMENTAL

Statin in the current prescribed dose

Drug: Statin in the evening (such as Simvastatin, Atorvastatin, Rosuvastatin, Pravastatin)

Statin in the morning

EXPERIMENTAL

Statin in the current prescribed dose

Drug: Statin in the morning (such as Simvastatin, Atorvastatin, Rosuvastatin, Pravastatin)

Interventions

Statin in the evening (such as Simvastatin, Atorvastatin, Rosuvastatin, Pravastatin) DRUG

Participants will be instructed to take their Statin daily at approx. 8PM-12AM.

Statin at bedtime

Statin in the morning (such as Simvastatin, Atorvastatin, Rosuvastatin, Pravastatin) DRUG

Participants will be instructed to take their statin upon awakening/or with their breakfast (approx. 6AM-10AM).

Statin in the morning

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• none

Sponsors & Collaborators

• Tor Biering-Sørensen: lead
• Herlev and Gentofte Hospital: collaborator

Study Sites (1)

Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Atorvastatin; Rosuvastatin Calcium; Pravastatin

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines

Central Study Contacts

Manan Pareek, MD and PhD

CONTACT

+4525536900; mananpareek@dadlnet.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, MPH

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: March 4, 2025
• Study Start: February 28, 2025
• Primary Completion (Estimated): March 28, 2028
• Study Completion (Estimated): March 28, 2028
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)