Early Diagnosis of Heart Failure Using NT-proBNP Levels in Primary Care

NCT07059260 | Not Yet Recruiting

• 1 other identifier: EARLY-BNP
• Study Type: interventional
• Target: 304
• Locations: 0 countries
• Sites: N/A

Brief Summary

Heart failure (HF) is a growing public health problem, expected to increase in prevalence and incidence due to population aging. This challenge is compounded by the healthcare overload following the COVID-19 pandemic, particularly in primary care (PC). Early diagnosis of HF is critical for improving outcomes, reducing complications, and optimizing resource use. However, there is no robust scientific evidence supporting the effectiveness of early screening for HF in PC settings. This study aims to evaluate whether an early cardiology assessment model for patients with suspected HF and elevated NT-proBNP levels (\>300 pg/mL) improves clinical outcomes compared to the standard referral pathway. The hypothesis is that early intervention will reduce emergency visits, hospitalizations, and mortality related to HF. This is a prospective, single-center, open-label, phase II randomized controlled trial with parallel group allocation (1:1). Patients presenting to PC with HF symptoms and no prior HF diagnosis, who have NT-proBNP levels \>300 pg/mL, will be invited to participate. After informed consent, participants will be randomized to one of two groups:

• Intervention group: Early cardiology assessment within 7 days.
• Control group: Standard referral by PC physician per usual care. Randomization will be computer-generated and managed independently to ensure allocation concealment. Patients will be followed for 12 months from the date of NT-proBNP testing. Outcomes will be collected through both cardiology and PC visits. Our primary outcome measure will be the clinical benefit, defined as a hierarchical composite endpoint of:
• Cardiovascular mortality
• All-cause mortality
• Number of hospitalizations due to HF
• Number of urgent care visits due to HF
• Number of GDMT (Guideline-Directed Medical Therapy) drugs initiated
• Number of GDMT drugs with dose escalation
• Proportional change in log (NT-proBNP) at 12 months
• Each component of the primary endpoint
• Stratified analysis by confirmed or excluded HF diagnosis
• Stratified analysis by HF phenotype (HFrEF vs HFpEF)
• Stratified analysis by sex A sample size of 304 patients (152 per group) has been calculated to detect a win ratio of 1.7 with 80% power, based on expected clinical benefit and statistical assumptions from prior literature. The study is expected to complete recruitment within 12 months, with a total study duration of 24 months including follow-up and data analysis.

Conditions

Heart Failure

Keywords

Heart Failure; Primary Care; Cardiology; NT-proBNP; proBNP

Outcome Measures

Primary Outcomes (1)

• Clinical benefit based on a hierarchical composite outcome (win ratio approach)

  Our primary outcome measure will be the clinical benefit, defined as a hierarchical composite endpoint of: 1. Cardiovascular mortality. 2. All-cause mortality. 3. Number of hospitalizations for heart failure (HF). 4. Number of urgent visits due to worsening HF symptoms requiring intravenous therapy, emergency department care or specialist evaluation. 5. Number of guideline-directed medical therapy (GDMT) drugs for HF initiated, if indicated (beta-blockers, RAAS inhibitors, SGLT2 inhibitors, MRAs). 6. Number of GDMT drugs with document dose up-titration (in those with indication). 7. Proportional 1-year change in plasma log(NT-proBNP) levels, as a biomarker of cardiac stress and congestion. The hierarchical structure of the primary endpoint and its components, along with the proposed statistical methodology, have been selected to ensure the feasibility of the study, efficient use of resources, and adequate statistical power.

  From enrollment, the patients will be followed 12 months

Secondary Outcomes (3)

• Stratified analysis of the primary endpoint in patients with elevated NT-proBNP, with a confirmed or ruled-out diagnosis of heart failure (HF).

  From enrollment, the patients will be followed 12 months

• Stratified analysis of the hierarchical clinical benefit composite endpoint by heart failure phenotype (HFpEF vs. HFrEF)

  From enrollment, the patients will be followed 12 months

• Stratified analysis of the hierarchical clinical benefit composite endpoint by sex (male vs. female)

  From enrollment, the patients will be followed 12 months

Study Arms (2)

Early referral

EXPERIMENTAL

This arm will be assessed following early referral by a cardiologist

Diagnostic Test: Early referral

Standard referral

NO INTERVENTION

This arm will be assessed following the standard referral by a cardiologist

Interventions

Early referral DIAGNOSTIC_TEST

The intervention involves early referral, allowing patients to be assessed by a cardiologist prior to the standard referral process. During this visit, the cardiologist will perform a comprehensive medical history and a detailed physical examination to assess signs of central and peripheral congestion. A standardized echocardiogram will also be conducted, including a series of objective measurements.

Early referral

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Signs and symptoms related to heart failure (HF).
• Patients assessed in primary care.
• No prior diagnosis of HF.
• NT-proBNP levels \> 300 pg/mL.

You may not qualify if:

• Patients diagnosed with a chronic disease with persistently elevated NT-proBNP levels, assessed by Cardiology, in whom heart failure (HF) has been ruled out in the previous year (mainly by echocardiography).
• Chronic kidney disease on hemodialysis.
• Patients with a life expectancy of less than 1 year due to severe comorbidities such as advanced-stage cancer.
• Patients enrolled in other clinical trials.
• Inability of the patient to understand the clinical trial and to provide informed consent.

Sponsors & Collaborators

• Maimónides Biomedical Research Institute of Córdoba: lead

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Enrique Enrile Sánchez

CONTACT

+34646678128; enriqueenrilesanchez@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, prospective, randomized, parallel-assignment, open-label, phase II interventional study. Patients with elevated NT-proBNP levels (\>300 pg/mL) and suspected heart failure in primary care are randomized 1:1 to early cardiology evaluation or standard care. Allocation concealment is ensured by independent randomization. Follow-up lasts 12 months to assess diagnosis, clinical events, and prognosis.

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 10, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-06