Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

NCT ID: NCT06820086

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE4
• Total Enrollment: 2500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-30
• Study Completion Date: 2033-02-28

Brief Summary

This research investigates the potential advantages of intensive preventive statin treatment for healthy men aged 45-80 and women aged 55-80 who possess a high genetic predisposition to coronary artery disease (CAD). By specifically targeting the top 20% of individuals with elevated CAD polygenic risk scores (PRS), the study seeks to find out whether this tailored approach can notably decrease the occurrence of cardiovascular disease and mortality over a five-year period when compared with usual care. Despite the potential of PRS in pinpointing individuals at heightened risk for cardiovascular disease, there is a lack of focused and prospective investigations in existing research. This study aims to bridge this gap by examining whether preventive statin therapy for individuals with high CAD PRS is not only effective in diminishing cardiovascular events but also economically viable. The comparison between the statin treatment arm and standard care practice is conducted in a pragmatic manner at the primary care level.

Conditions

PRS-based Primary Prevention of CVD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Intervention arm receiving statin treatment

Intervention arm participants (n=1250) comprise healthy men aged 45- 80 years and women aged 55-80 years with a high (top 20%) coronary artery disease (CAD) polygenic risk score.

They are prescribed by their primary care physician the trial medication, rosuvastatin 20mg, 1 tablet per day, for the entire duration of the trial. Intervention arm participants will be measured and regular blood analyses will be taken throughout the trial. They will be having regular primary care visits with their family physician and telemedicine visits with study nurses.

Group Type: EXPERIMENTAL

Rosuvastatin 20mg

Intervention Type: DRUG

Preventive statin treatment with rosuvastatin 20mg, 1 tablet per day, for healthy individuals with top 20% CAD PRS.

Control arm

Control arm participants (n=1250) comprise healthy men aged 45- 80 years and women aged 55-80 years with a high (top 20%) coronary artery disease (CAD) polygenic risk score.

Participants in the control arm of the trial will be following regular primary care as their family doctors will not be informed of their patients' participation in the trial. This means that in the control arm real-life primary care activities will take place including potential cholesterol-lowering treatment based on the current treatment and prevention guidelines. At the end of the trial, physicians will be informed about their patients who were in the control arm for scheduling a final study visit and ordering a blood test. During the final trial visit the physicians will inform participants of their CAD PRS, provide counselling and take final measurements.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Rosuvastatin 20mg

Preventive statin treatment with rosuvastatin 20mg, 1 tablet per day, for healthy individuals with top 20% CAD PRS.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Men aged 45-80 on 1 January 2025
• Women aged 55-80 on 1 January 2025
• CAD PRS top 20% confirmed by the Estonian Biobank (we intend to sample top 15% PRS individuals but we might have to also include 15-20% PRS individuals to fulfil the required sample size)
• The family physician of the study participant has been contracted to participate in the trial
• Written informed consent has been provided to participate in the trial

Exclusion Criteria

• Diagnosed with ischemic heart disease (I20-I25), stroke or transient ischemia (I60-64, I69, G45), peripheral vascular occlusion (I65-66, I67.2, I70, I73.9), diseases of liver (K70-K77), end stage renal disease (N18.0), mental and behavioural disorders due to psychoactive substance use (F10-F19).

-- The diagnosis must be present at least 2 times on a health claim or prescription within at least a 6-month period between 1.01.2022-31.12.2024.

• Currently using statin treatment:

• The individual has at least 1 prescription from ATC groups C10AA or C10BA between 01.01.2022- 31.12.2024.
• The individual has answered in the recruitment call that he/she is currently using statins or has been prescribed statins in the past 3 years.
• Has familiar hypercholesterolemia (APOB, PCSK9, LDLR genes verified by the Estonian biobank)
• Is currently participating in other clinical trials.
• Has been taking investigative trial medication during the past 30 days prior to study inclusion.
• Co-morbid physical or mental illnesses that prevent the individual from granting consent or participating in the trial (according to the judgement of the investigator).
• Individuals taking:

• a combination of sofosbuvir/velpatasvir/voxilaprevir (used to treat hepatitis C);
• ciclosporin
• fusidic acid orally or by injection.
• Individuals with a substance abuse disorder (alcohol, narcotic substances).
• Individuals with hypersensitivity to the active substance (rosuvastatin or atorvastatin) or its excipients.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Funding: European Union (the sponsor does not fund the study)

UNKNOWN

Sponsor Role: collaborator

The Estonian Health Insurance Fund

UNKNOWN

Sponsor Role: collaborator

North Estonian Medical Center

UNKNOWN

Sponsor Role: collaborator

Tartu University Hospital

OTHER

Sponsor Role: collaborator

Mikk JÜRISSON

OTHER

Sponsor Role: lead

Responsible Party

Mikk JÜRISSON

Associate professor of Public Health

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mikk Jürisson, PhD

Role: STUDY_DIRECTOR

Institute of Family Medicine and Public Health, University of Tartu

Aet Elken (Saar), PhD

Role: PRINCIPAL_INVESTIGATOR

Heart Clinic, Tartu University Hospital

Margus Viigimaa, PhD

Role: PRINCIPAL_INVESTIGATOR

North Estonia Medical Centre

Locations

North Estonia Medical Centre

Tallinn, Harju, Estonia

Tartu University Hospital

Tartu, Tartu, Estonia

Countries

Estonia

Other Identifiers

2024-513424-42-01

Identifier Type: CTIS

Identifier Source: secondary_id

EEPRS12308

Identifier Type: -

Identifier Source: org_study_id