Clinical trial NCT05919342: Screening for earlY Heart Failure Diagnosis and Management in Primary Care or at HOme Using Natriuretic Peptides and echocardiographY "SYMPHONY-HF"
Official title: Screening for earlY Heart Failure Diagnosis and Management in Primary Care or at HOme Using Natriuretic Peptides and echocardiographY
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Cardiovascular Diseases
Keywords: Screening
Biomarker
NT-proBNP
Echocardiography
Community
Registry
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: National Heart Centre Singapore
name: Karolinska University Hospital
name: Uppsala University
name: Montreal Heart Institute
name: Rigshospitalet, Denmark
name: University of British Columbia
name: The Cleveland Clinic
name: Université de Montréal
name: AstraZeneca
name: Roche Pharma AG
name: Us2.ai
First posted: 2023-06-26
Enrollment: 3904
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After agreeing to consent, patients will be randomised 1:1 to one of two arms; a "Routine care arm" in which patients will undergo routine care or a 2. "Investigational arm" - patients in this arm will have a blood sample performed for measurement of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Patients with an elevated Roche NT-proBNP (≥125 pg/mL) will undergo a transthoracic echocardiogram, clinical examination for signs of HF, HF symptom assessment, an ECG). Patients will undergo echocardiography with a CE-marked, FDA-approved handheld point of care (POC) EchoNous echocardiogram device in all countries. The US2.ai algorithm (which is also CE-marked and FDA-approved) will generate an AI-automated echocardiogram report. In Scotland all patients will also undergo a conventional echocardiogram. Patients who are classified as having heart failure (HFrEF, HFmrEF and HFpEF) will be referred for appropriate follow up.
Primary purpose: DIAGNOSTIC

Brief summary: This is an international prospective, multicentre, unblinded, randomised-controlled trial. The primary aim is to assess a targeted screening strategy to detect undiagnosed heart failure in high-risk patients.

Detailed description: The primary aim is to assess a targeted screening strategy to detect undiagnosed heart failure (HF) in high-risk patients.

Participants will be recruited from 5-countries (Denmark, Canada, United States of America, Sweden and Scotland). Individual patient data from similar national randomised controlled trials that are independently powered for different efficacy endpoints will be pooled, harmonised and analysed.

After agreeing to consent, patients will be randomised to one of two arms:

"Routine care arm" - patients in this arm will undergo routine care. They will be managed and followed up as per routine clinical care. They will be remotely monitored for HF events by follow up through electronic records and routinely collected data.

OR

"Investigational arm" - patients in this arm will have a blood sample performed for measurement of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Patients with an elevated Roche NT-proBNP (≥125 pg/mL) will undergo a transthoracic echocardiogram, clinical examination for signs of HF, HF symptom assessment, an ECG). Patients will undergo echocardiography with a CE-marked, FDA-approved handheld point of care (POC) EchoNous echocardiogram device in all countries. The US2.ai algorithm (which is also CE-marked and FDA-approved) will generate an AI-automated echocardiogram report. In Scotland all patients will also undergo a conventional echocardiogram. Patients who are classified as having heart failure (Heart failure with reduced ejection fraction \[HFrEF\], Heart failure with moderately reduced ejection fraction \[HFmrEF\] and Heart failure with preserved ejection fraction \[HFpEF\]) will be referred for appropriate follow up. In all countries when a handheld echocardiogram reported by AI-automated software does not provide diagnostic images a conventional echocardiogram will be undertaken.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥40 years of age
* Informed consent
* Two or more of the following risk factors for heart failure:

  1. Coronary artery disease (either a previous documented type 1 myocardial infarction or coronary artery bypass grafting or percutaneous coronary intervention or documented stenosis of an epicardial coronary artery \[50% left main stem or \>70% left anterior descending, circumflex or right coronary artery\])
  2. An established diagnosis of diabetes (type 1 or type 2)
  3. Persistent or permanent atrial fibrillation (not paroxysmal atrial fibrillation)
  4. Previous ischemic or embolic stroke
  5. Peripheral arterial disease (previous surgical or percutaneous revascularisation or a documented stenosis greater than 50% of a major peripheral arterial vessel).
  6. Chronic kidney disease (defined as an estimated glomerular filtration rate \<60mL/min/1.73m2 or eGFR 60-90mL/min/1.73m2 and UACR \>300mg/g).
  7. Regular loop diuretic use (any dose at any dosing interval) for \>30 days.
  8. COPD (evidenced by one of the following: PFTs showing airway obstruction, diagnosis by respiratory physician, CT scan reporting presence of emphysema or treatment with national guideline advocated COPD therapy).

Exclusion Criteria:

* Inability to give informed consent e.g., due to significant cognitive impairment
* Previous documented diagnosis of heart failure
* Current renal replacement therapy
* Anyone who, in the investigators' opinion, is not suitable to participate in the trial for other reasons e.g., a diagnosis which may compromise survival over the study period

Primary outcomes:
measure: Diagnosis of heart failure within 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Diagnosis of HFrEF within 6 months
timeFrame: 6 months
measure: People diagnosed with HFrEF receiving GDMT within 6 months
timeFrame: 6 months
Other outcomes:
measure: Diagnosis of HFmrEF within 6 months
timeFrame: 6 months
measure: Diagnosis of HFpEF within 6 months
timeFrame: 6 months
measure: People diagnosed with HFmrEF and HFpEF receiving SGLT2i therapy within 6 months
timeFrame: 6 months
measure: Diagnosis of asymptomatic left ventricular dysfunction (LVEF≤40%) within 6 months
timeFrame: 6 months
measure: Time to first heart failure hospitalisation at 1 year
timeFrame: 1 year
measure: Time to first heart failure hospitalisation at 2 years
timeFrame: 2 years
measure: Time to first heart failure hospitalisation at 5 years
timeFrame: 5 years
measure: All-cause mortality at 1 year
timeFrame: 1 year
measure: All-cause mortality at 2 years
timeFrame: 2 years
measure: All-cause mortality at 5 years
timeFrame: 5 years
measure: Time to first occurence of any components of the following clinical composite 1) heart failure hospitalisation 2) all-cause mortality at 1 year
timeFrame: 1 year
measure: Time to first occurence of any components of the following clinical composite 1) heart failure hospitalisation 2) all-cause mortality at 2 years
timeFrame: 2 years
measure: Time to first occurence of any components of the following clinical composite 1) heart failure hospitalisation 2) all-cause mortality at 5 years
timeFrame: 5 years
measure: The incremental cost-effectiveness ratio (ICER) will be expressed as incremental costs/life-year gained
timeFrame: 5 years
measure: The number of patients in the NT-proBNP/echocardiography group with echocardiographic features of potential amyloid as assessed by the US2.ai algorithm report conclusion of "amyloid to be considered"
timeFrame: 6 months
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Montréal
country: Canada
facility: University of Montreal
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Copenhagen University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University
city: Glasgow
country: United Kingdom
facility: University of Glasgow
state: Scotland
Study officials:
affiliation: University of Glasgow
name: Mark C Petrie, MbChB
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke-NUS Graduate Medical School
name: Carolyn SP Lam
role: PRINCIPAL_INVESTIGATOR
References: