Clinical trial NCT06820086: Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention
Official title: The Pragmatic EE-PRS Trial Assessing Polygenic Risk Driven Statin Therapy for Cardiovascular Disease Prevention
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: PRS-based Primary Prevention of CVD
Keywords: Polygenic Risk Score
Statin Treatment for Primary Prevention
High Polygenic Risk Score for Coronary Artery Disease
Lead sponsor: University of Tartu
Sponsor class: OTHER
Collaborators: name: Funding: European Union (the sponsor does not fund the study)
name: The Estonian Health Insurance Fund
name: North Estonian Medical Center
name: Tartu University Hospital
First posted: 2025-02-11
Enrollment: 2500
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Time to the first occurrence of Major Adverse Cardiovascular Events (MACE).
timeFrame: From enrollment to three years after the end of treatment.
Secondary outcomes:
measure: Incidence rate of death from any cause among the study participants
timeFrame: From enrollment to three years after the end of treatment.
measure: Change in CVD risk factors from baseline by the end of the trial in the intervention and control arm;
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Treatment adherence in the intervention arm.
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Fidelity of intervention implementation.
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Acceptability of the primary prevention program across study participants measured using an online questionnaire assessing satisfaction, perceived relevance, and ease of participation.
timeFrame: From first study visit to the end of treatment at 5 years.
measure: Satisfaction with study processes and results measured using an online questionnaire assessing satisfaction, perceived relevance, and ease of participation.
timeFrame: From study enrollment to the end of treatment at 5 years.
measure: Difference in plasma concentrations of rosuvastatin.
timeFrame: From enrollment to month 3 of treatment.
measure: Difference in rosuvastatin side effects.
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Utilisation of healthcare resources evaluated through a cost-utilty model
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Number of participants with adverse events and serious adverse events from statin therapy.
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Number of participants who withdrew or dropped out from the study.
timeFrame: From enrollment to the end of treatment at 5 years.
measure: Utilities from the EQ-5L-5D surveys and productivity costs from the iPCQ survey for calculating quality-adjusted life years (QALY) gained over a lifetime, incremental cost-effectiveness ratio (ICER).
timeFrame: From enrollment to the end of treatment at 5 years.
Other outcomes:
measure: Association of microbial species, functional diversity, and statin side effect risk, measured by species count and functional diversity.
timeFrame: From enrollment to three years after the end of treatment.
Locations:
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre
state: Harjumaa
city: Tartu
country: Estonia
facility: Tartu University Hospital
state: Tartumaa
Study officials:
affiliation: Institute of Family Medicine and Public Health, University of Tartu
name: Mikk Jürisson, PhD
role: STUDY_DIRECTOR
affiliation: Heart Clinic, Tartu University Hospital
name: Aet Elken (Saar), PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: North Estonia Medical Centre
name: Margus Viigimaa, PhD
role: PRINCIPAL_INVESTIGATOR
References: