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

Coronary Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04433052
• Other study ID #: CPP-2020-1
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2023
• Est. completion date: December 2026

Study information

• Verified date: June 2023
• Source: Tampere University
• Contact: Hanna Marttila, MSc
• Phone: +358407240771
• Email: hanna.marttila[@]tuni.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12000
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

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.

Locations

Country	Name	City	State
Finland	Helsinki University Hospital	Helsinki
Finland	Mehiläinen	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Hospital	Oulu
Germany	Klinik am See	Berlin
Germany	CCV-MVZ	Frankfurt
Germany	Heidelberg University	Mannheim
Germany	Technise Universität Munchen	München
Germany	Herzklinik Ulm	Ulm
Greece	Hellenic Red Cross Hospital	Athens
Greece	Konstantopoulio Hospital	Athens
Greece	Sismanoglion Hospital	Athens
Greece	The Biomedical Research Foundation of the Academy Athens	Athens
Italy	University Hospital Genova	Genova
Italy	Multi Medica, Care and Research Institute	Milan
Italy	Casilino Hospital Rome	Rome
Italy	University Hospital Turin	Turin
Poland	University of Bialystok	Bialystok
Poland	Medical University of Silesia	Katowice
Poland	Jagellonian University Medical College	Kraków
Poland	University of Lublin	Lublin
Poland	Nicolaus Copernicus University	Toruniak
Poland	National Institute of Cardiology	Warsaw
Portugal	Hospital de Santa Cruz-CHLO	Carnaxide
Portugal	Hospital do Espirito Santo	Lisbon
Portugal	Hospital Santa Maria-CHULN/FMUL	Lisbon

Sponsors (1)

Lead Sponsor	Collaborator
Tampere University

Countries where clinical trial is conducted

Finland,  Germany,  Greece,  Italy,  Poland,  Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	To evaluate the difference between PPP arm to the UC arm in	All-cause mortality	3 years follow-up
Secondary	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
Secondary	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
Secondary	• 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