Early Diagnosis of Heart Failure Using NT-proBNP Levels in Primary Care: The EARLY-BNP Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 304
- 主要终点
- Clinical benefit based on a hierarchical composite outcome (win ratio approach)
研究概览
简要总结
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
The primary analysis will use a win ratio methodology to maximize statistical efficiency and clinical interpretability.
Secondary outcomes include:
- 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.
详细描述
leads to better clinical outcomes compared to the usual referral pathway. Patients are randomized 1:1 to early cardiology evaluation (within 7 days of NT-proBNP result) versus standard PC-driven referral. This approach seeks to bridge the gap between suspicion and diagnosis, allowing for timely initiation or optimization of therapy when appropriate.
The study will be conducted in collaboration with the Córdoba-Guadalquivir Primary Care District. A training session has been held with primary care providers, and informed consent materials have been distributed throughout the district.
The primary outcome is a composite hierarchical endpoint, assessed using a win ratio approach. The components of this outcome include cardiovascular mortality, all-cause mortality, number of HF hospitalizations, number of urgent visits due to HF, number of GDMT drugs initiated (when indicated), number of GDMT drugs up-titrated (when indicated), and proportional change in log-transformed NT-proBNP at 12 months. The win ratio methodology allows for an ordered comparison of outcomes, giving greater weight to more severe events (e.g., death) while preserving statistical efficiency in detecting clinical benefit across multiple domains.
This design aligns with real-world priorities: reducing hard endpoints (mortality, hospitalization), improving evidence-based pharmacologic management, and optimizing biomarker control. It also recognizes the heterogeneity in HF diagnosis and severity among patients presenting to PC with unexplained dyspnea or fatigue.
The trial includes stratified secondary analyses in patients with and without confirmed HF, in those with HFpEF vs HFrEF phenotypes, and by sex, to explore differential responses to early intervention and inform future implementation strategies. All patients are followed for 12 months, with data collected from both cardiology and primary care visits. The target sample size of 304 participants provides adequate power to detect a clinically meaningful win ratio based on prior observational and interventional data. This total includes 152 patients per arm (early cardiology intervention vs. standard care), with a 1:1 allocation ratio
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Early referral
This arm will be assessed following early referral by a cardiologist
干预措施: Early referral (Diagnostic Test)
Standard referral
This arm will be assessed following the standard referral by a cardiologist
结局指标
主要结局
Clinical benefit based on a hierarchical composite outcome (win ratio approach)
时间窗: From enrollment, the patients will be followed 12 months
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.
次要结局
- 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)