Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

NCT06820086 | Enrolling By Invitation Phase 4 DMC

• 2 other identifiers: EEPRS123082024-513424-42-01
• Study Type: interventional
• Target: 2,500
• Locations: 1 country
• Sites: 2

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

Keywords

Polygenic Risk Score; Statin Treatment for Primary Prevention; High Polygenic Risk Score for Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Time to the first occurrence of Major Adverse Cardiovascular Events (MACE).

  Time to the first occurrence of Major Adverse Cardiovascular Events (MACE), ICD-10 codes: ischaemic heart disease (I20-I25), stroke or transient ischemia (I60-64, I69, G45), peripheral vascular occlusion (I65-66, I67.2, I70, I73.9), revascularization (Z95.1, Z95.5, Z95.8, Z95.9) or cardiovascular death (I00-78) from baseline.

  From enrollment to three years after the end of treatment.

Secondary Outcomes (12)

• Incidence rate of death from any cause among the study participants

  From enrollment to three years after the end of treatment.

• Change in CVD risk factors from baseline by the end of the trial in the intervention and control arm;

  From enrollment to the end of treatment at 5 years.

• Treatment adherence in the intervention arm.

  From enrollment to the end of treatment at 5 years.

• Fidelity of intervention implementation.

  From enrollment to the end of treatment at 5 years.

• Acceptability of the primary prevention program across study participants measured using an online questionnaire assessing satisfaction, perceived relevance, and ease of participation.

  From first study visit to the end of treatment at 5 years.

Other Outcomes (1)

• Association of microbial species, functional diversity, and statin side effect risk, measured by species count and functional diversity.

  From enrollment to three years after the end of treatment.

Study Arms (2)

Intervention arm receiving statin treatment

EXPERIMENTAL

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.

Drug: Rosuvastatin 20mg

Control arm

NO INTERVENTION

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.

Interventions

Rosuvastatin 20mg DRUG

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

Intervention arm receiving statin treatment

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Mikk JÜRISSON: lead
• Funding: European Union (the sponsor does not fund the study): collaborator
• The Estonian Health Insurance Fund: collaborator
• North Estonian Medical Center: collaborator
• Tartu University Hospital: collaborator

Study Sites (2)

North Estonia Medical Centre

Tallinn, Harju, Estonia

Location

Tartu University Hospital

Tartu, Tartu, Estonia

Location

MeSH Terms

Conditions

Genetic Risk Score

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mikk Jürisson, PhD

  Institute of Family Medicine and Public Health, University of Tartu

  STUDY DIRECTOR

• Aet Elken (Saar), PhD

  Heart Clinic, Tartu University Hospital

  PRINCIPAL INVESTIGATOR

• Margus Viigimaa, PhD

  North Estonia Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor of Public Health

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: February 11, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2033
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)