Novel Risk Prediction Approaches for the Primary Prevention of Cardiovascular Diseases in Italy: the CVRISK-IT Trial (CVRISK-IT) (CVRISK-IT)

January 12, 2026 updated by: Lorenzo Menicanti, IRCCS Policlinico S. Donato

Novel Risk Prediction Approaches for the Primary Prevention of Cardiovascular Diseases in Italy: the CVRISK-IT Trial

The CVRISK-IT study aims to evaluate the health benefit of measuring genetic and imaging risk information in men and women considered at 'low-to-moderate' or 'high' risk of developing cardiovascular diseases (CVD) in a randomized controlled trial in Italian primary care settings. Our primary objective is to answer a fundamental question in the prevention and prediction of CVD in Italy and globally: is there any benefit in including additional information (such as genetic and/or imaging data) in estimating risk, in conjunction with lifestyle advice and medical treatment for primary prevention of CVD?

As a key secondary objective of the CVRISK-IT study, the goal is to build a large bioresource with clinical information and biological samples to facilitate a new generation of discovery and translational research that will advance understanding of the genetic, molecular and behavioural determinants as well as mechanisms of multiple chronic diseases in the Italian population. By contributing to the Rete Cardiologica database and the BBDCARDIO biobank, the CVRISK-IT study will also serve as a cornerstone for future investigations into the development and testing of early diagnostic technologies and preventive (or 'personalised precision health') interventions for chronic diseases.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This multicenter, open randomized trial will investigate the effects of providing additional CVD risk information alongside personalised lifestyle advice and medical treatment in a primary prevention context across Italy. Healthy individuals aged 40 to 80 years, with no prior history of CVD or diabetes, will be recruited in two phases from the cohort of 17 participating IRCCS across Italy and affiliated enrolling centers. The population enrolled in this study consists of subjects who have never participated in other cardiovascular prevention studies of the Rete Cardiologica.

Phase 1 - Identification of the study population and development of the bioresource: various recruitment sources will be used, including institutions, primary care centres/services, government agencies, occupational health services, and volunteer organizations (e.g., blood donors). Participants will provide informed consent, a blood sample, and complete an electronic questionnaire. Approximately 30,000 individuals will be recruited and assessed using SCORE2/SCORE2-OP risk prediction models. Those identified as 'very high' risk will receive immediate medical treatment and will not proceed to phase 2.

Phase 2 - Randomization and novel risk prediction interventions: Participants identified as 'low-to-moderate' or 'high' CVD risk during phase 1 will be randomized, following a 2x2 factorial design into four groups within 1 week upon enrolment: a control group (no additional risk information), and three intervention groups (genetic, imaging-based and genetic + imaging-based risk information). The goal is to randomize around 12,000 participants in phase 2 (~3,000 per trial arm). All individuals will receive tailored lifestyle advice along with medical treatment based on their newly estimated CVD risk. The remaining 18,000 participants who won't proceed to phase 2 will still be involved in the study and contacted through a phone call follow-up with specialist at the 5◦ and 10◦ year.

Study Type

Interventional

Enrollment (Estimated)

30000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Ancona, Italy
        • Not yet recruiting
        • Irccs Inrca
        • Contact:
          • Roberto Antonicelli, MD
      • Genova, Italy
      • Milan, Italy
        • Recruiting
        • Irccs Ospedale San Raffaele
        • Contact:
      • Milan, Italy
      • Milan, Italy
      • Milan, Italy
      • Milan, Italy
      • Milan, Italy
      • Naples, Italy
      • Palermo, Italy
      • Pavia, Italy
      • Pavia, Italy
      • Pozzilli, Italy
      • Rome, Italy
      • Rome, Italy
      • San Donato Milanese, Italy
        • Recruiting
        • IRCCS Policlinico San Donato
        • Contact:
        • Contact:
          • Ambra Cerri, PhD
        • Principal Investigator:
          • Lorenzo Menicanti, MD
        • Sub-Investigator:
          • Emanuele Diangelantonio, MD
    • Milan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age: 40-80 years
  • Apparently healthy individuals without previous medical history of CVD or diabetes (based on medical diagnosis)
  • Participant recruitment arranged only at selected IRCCS (and associated Spokes) as part of the 'Rete Cardiologica'
  • Participants must have signed the Informed Consent and Data Privacy Treatment forms
  • Participants must have a personal e-mail address and internet connection

Exclusion Criteria:

  • Age ≤40 or ≥80 years
  • Individuals have previous medical history related to CVD (e.g., heart failure, congenital heart disorder, coronary heart disease) based on medical diagnosis
  • Candidates have previously participated in clinical studies of 'Rete Cardiologica' (e.g., PREVITAL)
  • Medical diagnosis of mental disorders
  • Pregnancy based on self-reported information
  • Previous history of type 1 or type 2 diabetes (based on medical diagnosis)
  • Oncology patients (based on physician indication)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
No additional cardiovascular risk information/recommendation is provided to the subject other than SCORE2/SCORE2-OP results of phase I. Thereby, the control group does not undergo neither imaging nor genetic analysis.
Experimental: Imaging
Subjects randomized in the imaging arm receive personalized recommendations on lifestyle and, if necessary, therapeutic intervention based on imaging data analysis (i.e., carotid ultrasound or calcium score)
Behavioral: Lifestyle Management
All individuals will receive tailored lifestyle advice along with medical treatment based on their newly estimated CVD risk. The control group will also receive lifestyle advice along with medical treatment based only on their CVD risk provided at the baseline visit during phase I.
Experimental: Polygenic Risk Score (PRS)
Subjects randomized in this arm receive personalized recommendations on lifestyle and, if necessary, therapeutic intervention based on polygenic risk score (PRS) analysis obtained from blood samples collected at the baseline visit
Behavioral: Lifestyle Management
All individuals will receive tailored lifestyle advice along with medical treatment based on their newly estimated CVD risk. The control group will also receive lifestyle advice along with medical treatment based only on their CVD risk provided at the baseline visit during phase I.
Experimental: Imaging and Polygenic Risk Score (PRS)
Subjects randomized in this arm receive personalized recommendations on lifestyle and, if necessary, therapeutic intervention based on both imaging data (e.g., carotid ultrasound and/or calcium score) and genetic analysis (e.g., PRS).
Behavioral: Lifestyle Management
All individuals will receive tailored lifestyle advice along with medical treatment based on their newly estimated CVD risk. The control group will also receive lifestyle advice along with medical treatment based only on their CVD risk provided at the baseline visit during phase I.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CVD risk using SCORE2/SCORE2-OP
Time Frame: 12 months
The primary short-term outcome (i.e., 12 months after communication of the newly estimated CVD risk, following the randomisation step) is the change in CVD risk measured using SCORE2/SCORE2-OP risk prediction models. The CVD risk categories used to classify healthy people according to these scores are: 1) Low-to-moderate CVD risk: <50 years = <2.5 %; 50-69 years = <5%; ≥ 70 years = <7.5%. High CVD risk: <50 years = 2.5 to <7.5%; 50-69 years = 5 to <10%; ≥ 70 years 7.5 to <15%; Very high CVD risk: <50 years = ≥7.5%; 50-69 years = ≥10%; ≥ 70 years = ≥ 15%.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in cardiovascular modifiable risk factors
Time Frame: 12 months
Secondary short-term outcomes will include changes in objectively measured risk factors, such as cholesterol levels (i.e., total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) (mg/dl)
12 months
Change in cardiovascular modifiable risk factors
Time Frame: 12 months
Secondary short-term outcomes will include changes in objectively measured risk factors, such as blood pressure which will be measured 3 times in a row, and its average calculated (mmHg)
12 months
Change in cardiovascular modifiable risk factors
Time Frame: 12 months
Secondary short-term outcomes will include changes in objectively measured risk factors, such as smoking habits (e.g., switch from "usual smoker" to "not smoking anymore" categories)
12 months
Change in CVD prevention-drugs prescription
Time Frame: 12 months
Secondary short-term outcomes will include changes in CVD prevention-drugs prescription with respect to the baseline visit
12 months
Evaluation of participant's adherence to ESC recommendations
Time Frame: 12 months
By means of validated questionnaires, the assessment of participants' adherence to the lifestyle and dietary guidelines of the European Society of Cardiology (ESC) will be performed. If and where applicable, drugs prescription adherence will be evaluated as well as psychological outcomes
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
CVD events recording in long-term period
Time Frame: 5-10 years
The long-term outcomes will include the registration of CVD events in all enrolled participants in the long-term period (e.g., non-fatal myocardial infarction, acute coronary syndrome, percutaneous transluminal coronary angioplasty (PTCA), Coronary artery bypass grafting (CABG), non-fatal stroke), CVD mortality, and total mortality
5-10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Policlinico S. Donato

Collaborators

IRCCS San Raffaele
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Istituto Clinico Humanitas
Istituto Auxologico Italiano
Istituto Di Ricerche Farmacologiche Mario Negri
Istituti Clinici Scientifici Maugeri SpA
Istituto Nazionale di Ricovero e Cura per Anziani
IRCCS Multimedica
Centro Cardiologico Monzino
Ospedale Policlinico San Martino
IRCCS San Raffaele Roma
Fondazione IRCCS Policlinico San Matteo di Pavia
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Istituto Neurologico Mediterraneo Neuromed S. R. L
IRCCS SYNLAB SDN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2025

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

February 4, 2025

First Submitted That Met QC Criteria

February 12, 2025

First Posted (Actual)

February 18, 2025

Study Record Updates

Last Update Posted (Estimated)

January 14, 2026

Last Update Submitted That Met QC Criteria

January 12, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CVRISK-IT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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