Clinical Value and Cost-effectiveness of a Personalized Prevention Program (PPP) in Patients With High Risk Stable CHD

A Prospective Clinical Trial to Evaluate the Clinical Value and Cost-effectiveness of a Personalized Prevention Program in Patients With High Risk Stable Coronary Heart Disease

Prospective clinical study with two parts:

PART A: a prospective biomarker-based risk screening study in coronary heart disease (CHD) subjects PART B: a nested randomized clinical trial (RCT) in an enriched subpopulation of high-risk stable CHD subjects

PART A: 12 000 subjects with stable CHD

PART B: 2000 subjects with high risk of CV events will be randomized to usual care (UC) or personalised prevention program (PPP) i.e. 1000 subjects per arm.

Study purpose is to assess the clinical value and cost-effectiveness of a personalised prevention program (PPP) in high-risk, stable coronary heart disease (CHD) subjects and to prospectively validate risk screening biomarkers

Study Overview

• Status: Recruiting
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Behavioral: personalised prevention program (PPP)

Detailed Description

Primary Objectives:

PART A:

• To prospectively validate biomarkers in risk stratification among stable CHD subjects, i.e. evaluation of the biomarker performance in accurately predicting CV events including CV death, nonfatal MI, HF events
• To identify high-risk CHD subjects for the subsequent RCT, i.e. 15-20% of the screened patient population at the highest risk

PART B

• To demonstrate whether a personalised prevention (PPP) strategy in high-risk CHD subjects results in a decreased risk of cardiovascular (CV) events (CV death, nonfatal myocardial infarction (MI) or heart failure (HF) events) as compared to the local usual care (UC)

Secondary Objectives:

• To evaluate the difference between the PPP arm to the UC arm as listed in section outcomes.
• To evaluate the health economic value of the PPP
• To prospectively study associations (in all enrolled subjects) between separate biomarkers (CERT2, hs-troponin, proBNP, Cystatin C) or their score (CoroPredict)

In addition to the above-listed primary and secondary objectives of the study, the following analysis will be carried out based on the data to be collected during the trial:

• Effect of personalised prevention on behavioural change.
• Effect of behavioural change on CV outcomes and blood pressure.
• Identification of key components and risk factors affecting effectiveness of the PPP.
• Inter-relationship between nutrition and exercise will be evaluated. Nutrition parameters will be based on questionnaires and biomarkers (Trimethylamine N-oxide (TMAO), Trimethyllysine (TML), carnitines and their metabolites).
• Effect of the use of the CoroPrevention Tool Suite (EXPERT tool) on the agreement between exercise prescriptions generated by cardiovascular nurses to subjects with CVD, and the ESC guideline-directed exercise prescriptions
• Effect of greater adherence to EXPERT tool-driven exercise prescriptions by clinicians and subjects, on CVD risk, physical fitness, and prognosis (hospitalisations, adverse events, mortality) in subjects with CVD.
• Effect of the use of the EXPERT tool-driven medication decision support system on the agreement between medication prescriptions generated by cardiovascular nurses to subjects with CVD, and the ESC guideline-directed medication prescriptions
• Effect of better adherence by both clinicians and subjects to ESC guideline prescriptions, driven by the medication decision support system within the EXPERT tool, on CVD risk and prognosis (hospitalisations, adverse events, mortality) in subjects with CVD.
• Investigation of the user experience and user acceptance of the CoroPrevention Tool Suite.

• Study Type: Interventional
• Enrollment (Estimated): 12000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hanna Marttila, MSc; Phone Number: +358407240771; Email: hanna.marttila@tuni.fi

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Hospital
    • Contact: Juha Sinisalo, MD, PhD; Email: juha.sinisalo@hus.fi
  • Helsinki, Finland
    • Recruiting
    • Mehilainen
    • Contact: Kristiina Hotakainen, MD, PhD; Email: Kristina.Hotakainen@mehilainen.fi
  • Kuopio, Finland
    • Not yet recruiting
    • Kuopio University Hospital
    • Contact: Juha Hartikainen, MD, PhD; Email: juha.hartikainen@kuh.fi
  • Oulu, Finland
    • Recruiting
    • Oulu University Hospital
    • Contact: Janne Hukkanen, MD, PhD; Email: janne.hukkanen@ppshp.fi
• Germany
  • Berlin, Germany
    • Not yet recruiting
    • Klinik am See
    • Contact: Heinz Völler, MD, PhD
  • Frankfurt, Germany
    • Withdrawn
    • CCV-MVZ
  • Mannheim, Germany
    • Not yet recruiting
    • Heidelberg University
    • Contact: Winfried März, MD, PhD
  • München, Germany
    • Not yet recruiting
    • Technise Universität Munchen
    • Contact: Martin Halle, MD, PhD
  • Ulm, Germany
    • Not yet recruiting
    • Herzklinik Ulm
    • Contact: Ralf Birkemeyer, MD, PhD
• Greece
  • Athens, Greece
    • Not yet recruiting
    • Hellenic Red Cross Hospital
    • Contact: Nikolaos Bourmpoulis, MD, PhD
  • Athens, Greece
    • Not yet recruiting
    • Konstantopoulio Hospital
    • Contact: Patsilinakos Sotirios, MD, PhD
  • Athens, Greece
    • Not yet recruiting
    • Sismanoglion Hospital
    • Contact: Dimitrios Sionis, MD, PhD
  • Athens, Greece
    • Not yet recruiting
    • The Biomedical Research Foundation of the Academy Athens
    • Contact: Constantinos Davos, MD, PhD; Email: cdavos@bioacademy.gr
• Italy
  • Genova, Italy
    • Not yet recruiting
    • University Hospital Genova
    • Contact: Itolo Porto, MD, PhD; Email: italo.porto@unige.it
  • Milan, Italy
    • Not yet recruiting
    • Multi Medica, Care and Research Institute
    • Contact: Roberto FE Pedretti, MD, PhD
  • Rome, Italy
    • Not yet recruiting
    • Casilino Hospital Rome
    • Contact: Leonardo Calo, MD, PhD
  • Turin, Italy
    • Not yet recruiting
    • University Hospital Turin
    • Contact: Gaetano de Ferrari, MD, PhD; Email: gaetanomaria.deferrari@unito.it
• Poland
  • Białystok, Poland
    • Not yet recruiting
    • University of Bialystok
    • Contact: Karol Kaminski, MD, PhD
  • Katowice, Poland
    • Not yet recruiting
    • Medical University of Silesia
    • Contact: Zbigniew Gasior, MD, PhD; Email: zgasior@ptkardio.pl
  • Kraków, Poland
    • Not yet recruiting
    • Jagellonian University Medical College
    • Contact: Piotor Jankowski, MD, PhD; Email: piotrjankowski@interia.pl
  • Lublin, Poland
    • Not yet recruiting
    • University of Lublin
    • Contact: Andrzej Wysokinski, MD, PhD
  • Toruniak, Poland
    • Not yet recruiting
    • Nicolaus Copernicus University
    • Contact: Aldona Kubica, MD, PhD
  • Warsaw, Poland
    • Not yet recruiting
    • National Institute of Cardiology
    • Contact: Rafal Dabrowski, MD, PhD
• Portugal
  • Carnaxide, Portugal
    • Not yet recruiting
    • Hospital de Santa Cruz-CHLO
    • Contact: Miguel Mendes, MD, PhD
  • Lisbon, Portugal
    • Not yet recruiting
    • Hospital do Espirito Santo
    • Contact: Lino Patricio, MD, PhD
  • Lisbon, Portugal
    • Not yet recruiting
    • Hospital Santa Maria-CHULN/FMUL
    • Contact: Ana Abreu, MD, PhD; Email: ananabreu@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Eligible study subjects must meet all of the following inclusion criteria:

1. Informed consent form signed by the study subjects.
2. Male or female aged 30 to 80 years on the day of enrolment.
3. > 50% stenosis in one or more major coronary arteries on angiography or computerised tomography (CT) performed within the preceding one year (from enrolment visit).

or Myocardial infarction (type I, II) during the preceding year.

Eligible study subjects must not meet any of the following exclusion criteria:

1. Hospitalisation for acute coronary syndrome, myocardial infarction, stroke, coronary revascularisation or acute heart failure within the preceding one month (30 days). These subjects can be enrolled after a one-month stabilisation period, which begins from the time of the event.
2. Subjects with NYHA class III-IV heart failure i.e. marked limitation in activity due to symptoms, comfortable only at rest.
3. Uncontrolled arrhythmias such as ventricular tachycardias.
4. Subjects undergoing dialysis due to severe renal disease.
5. Diseases that severely disable exercising (per investigator's judgement), such as rheumatoid arthritis, neurological or orthopaedic diseases.
6. Known aplastic or haemolytic anaemia.
7. Concomitant non-coronary disease, such as malignancy that limits life expectancy to less than three years.
8. Concurrent participation in another interventional study.
9. Subjects not able and/or willing to attend all scheduled visits and comply with all study procedures and use a smartphone application.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalised prevention program (PPP); Participants will be invited to return to the study site six times over a three year period to receive lifestyle coaching and exercise prescriptions. Eupropean Society of Cardiology/European Association of Preventive Cardiology (ESC/EAPC) -designed lifestyle counselling will be partially delivered by novel smartphone applications. Participants will also receive pharmaceutical treatment according to the ESC guideline for chronic coronary syndromes.	Behavioral: personalised prevention program (PPP); Study subjects in the PPP arm will be invited to return to the study site six times over a three-year period (at V2/start of the study, V3/mo2, V4/mo6, V5/mo12, V6/mo18 and V7/mo36) to receive lifestyle coaching and exercise prescriptions led by a delegated member of the site staff and supervised by the investigator. Information on drug treatment will also be given by the investigator. These activities will be assisted by digital tools specifically designed for this study, the CoroPrevention Tool Suite.
No Intervention: Usual care (UC); Participants will be referred back to usual care provided by their treating physicians. It is anticipated that physicians will treat these participants according to local usual medical practices. Patients randomized to UC group will not receive any treatment recommendations nor restrictions by the study investigators or nurses. Randomized UC patients are invited to site visits twice over a three year period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate whether a PPP strategy in high-risk CHD subjects results in a decreased risk of CV events (CV death, nonfatal MI or HF events) compared to the UC	• The time from randomisation to the occurrence of the first CV event included in the composite endpoint of the study (CV death, nonfatal MI, HF events) over 3 years follow-up.	3 years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the difference between PPP arm to the UC arm in	o The times from randomisation to the occurrence of the specific items included in the composite endpoint (CV death, nonfatal MI, HF event) over 3 years follow-up	3 years follow-up
To evaluate the difference between PPP arm to the UC arm in	o The times from randomisation to the occurrence of secondary CV events (unstable angina, stroke and coronary revascularisations excluding those elective revascularisations that have been planned prior to randomisation)	3 years follow-up
To evaluate the difference between PPP arm to the UC arm in	o Treatment adherence; measured by compliance laboratory assessments and in the PPP group, also with activity reports	3 years follow-up
To evaluate the difference between PPP arm to the UC arm in	All-cause mortality	3 years follow-up
To evaluate the difference between PPP arm to the UC arm in	Incidence of additional clinical endpoints: diabetes mellitus type 2 (DM2), chronic kidney disease (CKD), peripheral artery disease (PAD) and hypertension	3 years follow-up
To evaluate the health economic value of the PPP	o A cost-effectiveness analysis of PPP versus UC will be undertaken, based on evidence from the randomised clinical trial (RCT) portion of the study, using within-trial analysis and long-term cost-effectiveness modelling for the six countries participating in the CoroPrevention trial: Finland, Poland, Greece, Portugal, Italy, and Germany.	3 years follow-up
• To prospectively study associations (in all enrolled subjects) between separate risk biomarkers (CERT2, hs-troponin , proBNP, Cystatin C) or their score (CoroPredict) and	Primary composite CV event (CV death, MI, HF events); Specific CV events (CV death, nonfatal MI, HF events) separately; Specific secondary CV events (unstable angina, stroke, coronary revascularisations); Incidence of DM2, CKD, PAD and hypertension	3 years follow-up

Collaborators and Investigators

• Sponsor: Tampere University
• Investigators: Study Director: Reijo Laaksonen, MD, PhD, Tampere University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Prevention; Biomarkers; Lifestyle; Coronary Heart Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: CPP-2020-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: EU open access policy
• IPD Sharing Time Frame: opens 2 years after last study patient visit, open for 18 years until IPD deletion
• IPD Sharing Access Criteria: Steering Committee decision, application needed

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