NT-proBNP Screening for Heart Failure

(SYMPHONY-HF Trial)

Recruiting at 6 trial locations

Overseen By Kieran F Docherty, MbChB

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NHS Greater Glasgow and Clyde

Must be taking: Loop diuretics

Disqualifiers: Heart failure, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

3904 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment NT-proBNP for heart failure?

Research shows that NT-proBNP is useful in diagnosing and managing heart failure, as it helps identify patients with heart problems and predict their prognosis. It is considered a reliable marker due to its stability in the blood, making it effective for detecting and evaluating heart failure. ^{1 2 3 4 5}

Is NT-proBNP safe for humans?

The research does not provide specific safety data for NT-proBNP, but it is widely used as a biomarker (a biological marker used to measure and evaluate physiological processes) in diagnosing and managing heart failure, suggesting it is generally considered safe for these purposes. ^{4 6 7 8 9}

How does NT-proBNP screening differ from other heart failure treatments?

NT-proBNP screening is unique because it uses a biomarker to help diagnose and manage heart failure, rather than directly treating the condition. This approach can improve diagnostic accuracy and patient care by identifying heart failure earlier and more reliably than traditional methods. ^{2 5 9 10 11}

Research Team

Carolyn SP Lam

Principal Investigator

Duke-NUS Graduate Medical School

Mark C Petrie, MbChB

Principal Investigator

University of Glasgow

Eligibility Criteria

This trial is for adults over 40 with persistent atrial fibrillation and a history of stroke, plus two or more risk factors like coronary artery disease, diabetes, peripheral arterial disease, chronic kidney disease, regular use of loop diuretics, or COPD. It's not for those who can't consent, are on renal replacement therapy, have known heart failure or other conditions that may limit survival during the study.

Inclusion Criteria

I have had surgery or a procedure for blocked arteries in my legs.

Informed consent

I have had a heart attack or surgery/intervention for blocked heart arteries.

Exclusion Criteria

I am able to understand and agree to the study's procedures and risks.

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

I am on dialysis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization

Participants are randomized into either the routine care arm or the investigational arm

1 week

Investigational Arm

Participants in this arm will have a blood sample performed for NT-proBNP measurement. Elevated levels lead to further diagnostic tests including echocardiograms and clinical examinations.

4-6 weeks

Routine Care Arm

Participants in this arm will undergo routine care and be monitored for heart failure events through electronic records.

4-6 weeks

Follow-up

Participants are monitored for heart failure events and outcomes through electronic records and routinely collected data.

6 months

Treatment Details

Interventions

• NT-proBNP

Trial Overview SYMPHONY-HF aims to test if screening high-risk patients using NT-proBNP (a marker in the blood) and echocardiography can help detect undiagnosed heart failure early. Participants will be randomly assigned to receive this targeted screening strategy.

Participant Groups

Group I: Investigational arm Experimental Treatment 1 Intervention

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.

Group II: Routine care arm Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

NHS Greater Glasgow and Clyde

Lead Sponsor

Trials

295

Recruited

333,000+

University of Glasgow

Collaborator

Trials

362

Recruited

24,980,000+

National Heart Centre Singapore

Collaborator

Trials

78

Recruited

7,455,000+

Karolinska University Hospital

Collaborator

Trials

509

Recruited

1,319,000+

Uppsala University

Collaborator

Trials

529

Recruited

3,333,000+

Montreal Heart Institute

Collaborator

Trials

125

Recruited

85,400+

Rigshospitalet, Denmark

Collaborator

Trials

1,343

Recruited

2,453,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

Findings from Research

In a study of 594 participants, elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at screening were found to significantly increase the risk of heart failure, with an 18-fold increase when levels were 150 pg/mL or above.

Participants with NT-proBNP levels ≥150 pg/mL had a 10-year survival rate of only 61%, compared to 89% for those below this threshold, indicating that high NT-proBNP levels are not only predictive of heart failure but also associated with a higher risk of death within a decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of NT-proBNP in screening for and predicting prognosis in heart failure: a survival analysis. Taylor, CJ., Roalfe, AK., Iles, R., et al.[2022]

In a study of 76 patients, the NT-proBNP level of less than 300 pg/ml demonstrated a high sensitivity of 97% for excluding heart failure (HF), making it a reliable diagnostic tool.

The negative predictive value of 94% indicates that patients with NT-proBNP levels below this threshold are unlikely to have HF, supporting the use of this cut-off point in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnostic usefulness of N-terminal brain natriuretic peptide in patients admitted to a cardiology service]. Farráis Villalba, M., Rodríguez Esteban, M., de las Heras, S., et al.[2019]

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels are reliable biomarkers for diagnosing heart failure (HF), as low levels can effectively rule out the condition.

The systematic review included 310 articles, highlighting that BNP and NT-proBNP are not only useful for diagnosis but also provide prognostic information and can guide treatment decisions in heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of BNP and NT-proBNP in the management of heart failure: overview and methods. Oremus, M., McKelvie, R., Don-Wauchope, A., et al.[2022]

In a study of 28 children with congestive heart failure (CHF), plasma NT-proBNP levels were significantly higher than in age-matched controls, indicating its potential as a diagnostic tool for CHF in children.

The study found that NT-proBNP levels correlated positively with the modified Ross score, which assesses heart failure severity, suggesting that NT-proBNP could also be useful for evaluating the severity of heart failure in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic usefulness of N-terminal pro-brain natriuretic peptide among children with heart failure in a tertiary hospital in Lagos, Nigeria. Ekure, EN., Okoromah, CA., Ajuluchukwu, JN., et al.[2019]

In a study of 105 patients with chronic heart failure, N-terminal proBNP (NT-proBNP) levels increased more significantly than BNP levels as the severity of heart failure (measured by NYHA classification) worsened, indicating NT-proBNP may be a better marker for assessing heart failure severity.

Receiver operating characteristic analysis suggested that NT-proBNP is at least as effective as BNP in detecting reduced left ventricular ejection fraction (LVEF), with a higher area under the curve for NT-proBNP when detecting LVEF<50%, suggesting it could be a more reliable diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of NT-proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure. Seino, Y., Ogawa, A., Yamashita, T., et al.[2022]

The Roche Elecsys 2010 assay demonstrated superior precision and stability for measuring NT-proBNP compared to the Abbott AxSYM method, with lower coefficient of variation (CV) values (0.9% to 2.2% vs. 3.7% to 12.7%).

Both assays are not fully specific for diagnosing congestive heart failure (CHF), but the Elecsys 2010 method showed a higher area under the ROC curve (0.841) compared to the AxSYM method (0.704), indicating better diagnostic performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP. Chien, TI., Chen, HH., Kao, JT.[2011]

In a study of 368 patients with stable chronic heart failure, the optimal interval for monitoring NT-proBNP levels was found to be approximately 7.9 months, indicating a significant signal of disease progression over biological variability.

The monitoring interval can be adjusted based on individual risk levels, with lower-risk patients potentially benefiting from longer intervals between NT-proBNP measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure. Dai, Z., Asano, T., Takahashi, O., et al.[2021]

In a study of 14,737 patients with heart failure and reduced ejection fraction, higher NT-proBNP plasma concentrations were strongly associated with increased rates of cardiovascular (CV) deaths, showing a steep rise from 33.8 to 142.3 deaths per 1000 patient-years as NT-proBNP levels increased from ≤400 to ≥3000 pg/mL.

In contrast, the rates of non-CV deaths and hospitalizations increased only modestly, indicating that NT-proBNP levels are more predictive of CV risks than non-CV risks, which could influence future clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic peptide plasma concentrations and risk of cardiovascular versus non-cardiovascular events in heart failure with reduced ejection fraction: Insights from the PARADIGM-HF and ATMOSPHERE trials. Khan, MS., Kristensen, SL., Vaduganathan, M., et al.[2021]

In a study of 477 patients with acute dyspnea, the use of NT-proBNP testing in the emergency department significantly reduced the median time to discharge from 3.9 days to 1.9 days, indicating improved patient management.

The introduction of NT-proBNP testing also suggested a trend towards reduced hospital admission costs, saving approximately $1,364 per patient, while maintaining similar 30-day mortality rates between the testing and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-terminal pro-brain natriuretic peptide testing in the emergency department: beneficial effects on hospitalization, costs, and outcome. Rutten, JH., Steyerberg, EW., Boomsma, F., et al.[2015]

NT-proBNP is a valuable biomarker for diagnosing and managing heart failure (HF), providing important prognostic information for patients with this condition.

Research suggests that NT-proBNP may also have potential applications beyond cardiovascular diseases, indicating its broader relevance in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of N-terminal pro B-type natriuretic peptide in heart failure and other cardiovascular diseases. Pu, DR., Chiong, JR., Zhou, QC.[2021]

In a study of 202 patients with dyspnea, those with arterial hypertension had significantly higher NT-proBNP levels (median 123 pg/mL) compared to normotensive individuals (median 77 pg/mL), indicating that hypertension affects NT-proBNP levels.

The difference in NT-proBNP levels between hypertensive and normotensive patients diminished when excluding those with diastolic dysfunction, suggesting that hypertension may confound the specificity of NT-proBNP as a diagnostic marker for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[NT-proBNP levels and hypertension. Their importance in the diagnosis of heart failure]. Rivera, M., Taléns-Visconti, R., Salvador, A., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

The potential role of NT-proBNP in screening for and predicting prognosis in heart failure: a survival analysis. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

[Diagnostic usefulness of N-terminal brain natriuretic peptide in patients admitted to a cardiology service]. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

A systematic review of BNP and NT-proBNP in the management of heart failure: overview and methods. [2022]

4. Nigeria pubmed.ncbi.nlm.nih.gov

Diagnostic usefulness of N-terminal pro-brain natriuretic peptide among children with heart failure in a tertiary hospital in Lagos, Nigeria. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Application of NT-proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP. [2011]

7. England pubmed.ncbi.nlm.nih.gov

The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Natriuretic peptide plasma concentrations and risk of cardiovascular versus non-cardiovascular events in heart failure with reduced ejection fraction: Insights from the PARADIGM-HF and ATMOSPHERE trials. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

N-terminal pro-brain natriuretic peptide testing in the emergency department: beneficial effects on hospitalization, costs, and outcome. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical applications of N-terminal pro B-type natriuretic peptide in heart failure and other cardiovascular diseases. [2021]

11. Spain pubmed.ncbi.nlm.nih.gov

[NT-proBNP levels and hypertension. Their importance in the diagnosis of heart failure]. [2016]