Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruitment ended
Participants planned
2,500
Countries
1
Sites
2
High polygenic risk for coronary artery disease
To assess the effectiveness of preventive statin treatment based on high coronary artery disease polygenic risk (CAD PRS) on reducing the incidence of cardiovascular events and death.
Key facts
- Sponsor
- University Of Tartu
- Participant type
- Healthy volunteers
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 25 Mar 2025 → ongoing
- Decision date (initial)
- 2024-12-19
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- European Union Horizon Europe · Estonian Health Insurance Fund (Tervisekassa)
External identifiers
- EU CT number
- 2024-513424-42-01
- ClinicalTrials.gov
- NCT06820086
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacogenomic, Efficacy, Pharmacoeconomic, Safety
To assess the effectiveness of preventive statin treatment based on high coronary artery disease polygenic risk (CAD PRS) on reducing the incidence of cardiovascular events and death.
Secondary objectives 6
- To assess the effect of the trial interventions on lowering cardiovascular risk factors.
- To assess the adherence and acceptability to preventive statin treatment among high- CAD PRS individuals.
- To assess the plasma concentration and safety of statin therapy depending on the presence of various gene mutations (in SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes).
- To assess the bidirectional relationship between statin therapy and the gut microbiome, specifically focusing on two intertwined aspects: (1) the mechanisms by which statins modulate gut microbiome composition and function, and (2) the influence of the gut microbiome on the therapeutic efficacy of statins.
- To assess the resource use, cost, and cost-utility of preventive statin treatment based on CAD PRS compared to the standard of practice in primary care.
- To assess the acceptance and motivation to prescribe preventive statin treatment based on CAD PRS among family physicians.
Conditions and MedDRA coding
High polygenic risk for coronary artery disease
Regulatory references
- Plan to share IPD
- Yes
- IPD plan description
- Our external partner (Institute for Medical Technology Assessment, Erasmus School of Health Policy and Management, Erasmus University Rotterdam) will be granted access to performing cost-effectiveness analysis to pseudonymized study data via the SAPU virtual environment (https://sapu.cs.ut.ee) managed by the EBB. This is a virtual server with limited access to the Internet. It is possible to process data there with the software installed on the server, but there are limitations on the data that can be taken off the server. Data cannot be downloaded from the server or uploaded to an external web server. Even copying text, images, and files is only possible inside the environment, not outside. The only way to pull data out is through a unique file management system where the server administrator (EBB) can review the files being output and determine if the files being output comply with the restrictions imposed by law and the ethics committee's permissions.
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-513424-42-00 | From Genes to Hearts: Evaluating the Effectiveness of a Polygenic Risk Driven Statin Therapy for Cardiovascular Disease Prevention | University Of Tartu |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Men aged 45-80 on 1st of January 2025
- Women aged 55-80 on 1st of January 2025
- CAD PRS top 20% confirmed by the Estonian Biobank
- 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 9
- - 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.
- - 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.
- - 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.
- - Individuals with a substance abuse disorder (alcohol, narcotic substances).
- - Individuals with hypersensitivity to the active substance (rosuvastatin or atorvastatin) or its excipients.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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.
Secondary endpoints 13
- - Incidence rate of death from any cause among the study participants.
- - Change in CVD risk factors from baseline (LDL-cholesterol, blood pressure, BMI, waist circumference, smoking, alcohol consumption prevalence) by the end of the trial in the intervention and control arm.
- - Treatment adherence in the intervention arm based on prescriptions and purchases of statins (C10AA, C10BA) and self-reporting using the MARS-5 scale.
- - Fidelity of implementation assessed by participant feedback, and adherence to program activities (record analysis).
- - Acceptability of the primary prevention program across study participants.
- - Satisfaction with study processes and results.
- Difference in plasma concentrations of rosuvastatin comparing study participants with and without a mutation in the SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes.
- Difference in rosuvastatin side effects between study participants with and without a mutation in the SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes.
- Difference in side effects and overall trial outcomes depending on gut microbiome composition and functionality.
- Utilisation of healthcare resources (non-trial physician and cardiologist visits, hospitalizations, length of stay, health care and informal resource use, direct healthcare costs.)
- - Number of participants with adverse events and serious adverse events from statin therapy.
- - Number of participants who withdrew or dropped out from the study.
- - 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).
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
SUB05600MIG · Substance
- Active substance
- Atorvastatin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 60 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20634 · Substance
- Active substance
- Rosuvastatin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20634 · Substance
- Active substance
- Rosuvastatin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
University Of Tartu
- Sponsor organisation
- University Of Tartu
- Address
- Ravila Tn 19
- City
- Tartu Linn
- Postcode
- 50411
- Country
- Estonia
Scientific contact point
- Organisation
- University Of Tartu
- Contact name
- Mikk Jürisson
Public contact point
- Organisation
- University Of Tartu
- Contact name
- Mikk Jürisson
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Estonia | Ongoing, recruitment ended | 2,500 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
Tartu University Hospital
Heart Clinic, L. Puusepa Tn 1a, 50406, Tartu Linn
North Estonia Medical Centre Foundation
Cardiology, J. Sutiste Tee 19, Mustamae Linnaosa, Tallinn
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Estonia | 2025-03-25 | 2025-03-25 | 2026-01-07 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-89840
- Sponsor became aware
- 2025-06-25
- Date of breach
- 2025-06-05
- Submission date
- 2025-07-09
- Member states concerned
- Estonia
- Categories
- Protocol
- Areas impacted
- Data reliability or robustness
- Benefit-risk balance changed
- No
- Description
- The breach is related to the errenous deletion of all data for 15 randomised study participants (post-consent and pre-visit data collection).
After the digitally signed informed consent had been received, the 15 individuals were randomised to the study, and their data were entered into the study database REDCap.
Before the first study visit (i.e., before the start of data collection), these study participants opted out of the trial. They contacted the Estonian Biobank’s IT department, explaining that they wished to opt out of the trial before data collection began. The breach occurred because the IT department, based on GDPR, interpreted that the digitally signed study participation consent form and information about the study participant in REDCap must be deleted. The IT department then deleted all data (digitally signed consent forms from the Estonian Biobank’s server and study participant data collection forms from REDCap).
Impact of the serious breach:
This loss of data for 15 individuals can impact the robustness of our intention-to-treat analyses at the end of the trial.
The full impact assessment is available in the attached document. - Sponsor actions
- Available in the attached document. An overview:
1) Assess possibility of partial restoration from system backups:
- The PI will contact the IT Lead from the EstBB to investigate potential data restoration. (Within 2 weeks)
2) Draft and implement a Standard Operating Procedure (SOP) that clearly distinguishes between:
- Opt-out before data collection
- Withdrawal after data collection
- Formal GDPR erasure requests (Within 4 weeks)
3) Deletion Approval Workflow:
- Implement a role-based, review-and-approval workflow in REDCap (or other study systems) for any deletion of study data or consent documentation. (Within 4 weeks)
| Organisation | City | Country | Type |
|---|---|---|---|
| University Of Tartu | Tartu Linn | Estonia | Other |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 19 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_PROTOCOL_2024-513424-42-01 | 1 |
| Protocol (for publication) | D1_PROTOCOL_2024-513424-42-01_v2_5 | 2.5 |
| Protocol (for publication) | D1_PROTOCOL_2024-513424-42-01_v2_6 | 2.6 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF EST | 2.1 |
| Subject information and informed consent form (for publication) | L1_ICF RUS | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS EST_18_12 | 2.2 |
| Subject information and informed consent form (for publication) | L1_SIS RUS_18_12 | 2.2 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material email text EST | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material email text RUS | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material gene donor portal intro text EST | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material gene donor portal intro text RUS | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material SMS EST | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material travel reimbursement EST | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material travel reimbursement RUS | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_stool sample guide_EST | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_stool sample guide_RUS | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC atorvastatin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC rosuvastatin | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-04 | Estonia | Acceptable 2024-12-18
|
2024-12-19 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2026-04-14 | Estonia | Acceptable 2026-05-13
|
2026-05-13 |