Guiding Evidence Based Therapy Using Biomarker Intensified Treatment

Study Overview
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Brief Summary
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The primary objective is to determine the efficacy of a strategy of biomarker-guided therapy compared with usual care in high risk patients with left ventricular systolic dysfunction.

Detailed Description
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Heart failure is a common disorder in which the heart cannot pump enough blood to meet the needs of the rest of the body. Common symptoms of heart failure include shortness of breath, swelling, and fatigue. Standard treatment for heart failure include diuretics to control fluid, as well as drugs called neurohormonal antagonists (such as beta-blockers and ACE-inhibitors) that help the heart work more efficiently and prevent worsening of heart function. Typically, doctors adjust these medicines based on their clinical judgment about what doses and combination will work best for you. We are testing whether the use of a blood test called NT-proBNP (which measures a hormone released by the heart) can help doctors do a better job of adjusting these heart failure medicines over time than clinical judgment alone.

Official Title
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Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Usual Care
* Device: Biomarker-guided care NT-proBNP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Most recent LVEF to be ≤ 40% by any method within 12 months of randomization. High risk heart failure as defined by the following criteria: A Heart Failure Event in the prior 12 months, defined as any one of the following: HF Hospitalization Treatment in the Emergency Department (or equivalent) for Heart Failure Outpatient treatment for heart failure with intravenous diuretics AND NT-proBNP greater than 2000 pg/mL or BNP greater than 400 pg/mL at any time during the 30 days prior to randomization Willing to provide informed consent Exclusion Criteria: Acute coronary syndrome (clinical diagnosis) or cardiac revascularization procedure within 30 days Cardiac resynchronization therapy (CRT) within prior 3 months or current plan to implant CRT device Active myocarditis, Hypertrophic obstructive cardiomyopathy, pericarditis, or restrictive cardiomyopathy Severe stenotic valvular disease Anticipated heart transplantation or ventricular assist device within 12 months Chronic inotropic therapy Complex congenital heart disease End stage renal disease with renal replacement therapy Non cardiac terminal illness with expected survival less than 12 months Women who are pregnant or planning to become pregnant Inability to comply with planned study procedures Enrollment or planned enrollment in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Usual Care<br>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure. | Other: Usual Care<br>* Usual Care<br>|
| Experimental: Biomarker-Guided Care<br>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses. | Device: Biomarker-guided care NT-proBNP<br>* Device: NT-proBNP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CV Death or Heart Failure Hospitalization | Composite of First Heart Failure Hospitalization or Cardiovascular Mortality | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | All-cause mortality by treatment arm | 24 months | 
| Cumulative Morbidity | Days alive and not hospitalized for CV reasons | 24 months | 
| CV Death | CV death by treatment arm | 24 months | 
| Number of Hospitalizations for First Heart Failure | First Heart Failure Hospitalization | 24 months | 
| Number of Hospitalizations for Recurrent Heart Failure | Recurrent Heart Failure Hospitalization | 24 months | 
| Percentage of Patients With Moderate to Severe Depression | Percentage of patients with moderate to severe depression as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). CES-D is a 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression. Moderate to severe depression is indicated by a score of 11 or higher. | Baseline, 3,6, 12 and 24 months | 
| Duke Activity Status Index (DASI) | The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity). | Baseline, 3, 6, 12 and 24 months | 
| EQ-5D Health Index | The EQ-5D measures the subjects health status in 5 categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and totals them into 1 score, from -0.59 (worst) to 1 (best). | Baseline, 3, 6, 12 and 24 months | 
| EQ-5D Visual Analog Scale | The EQ-5D VAS records participants self-rated health status on a vertical (0-100) scale with higher scores indicating higher Health-Related Quality of Life, where 0 = worst imaginable health state and 100 = best imaginable health state. | Baseline, 3, 6, 12 and 24 months | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score | This KCCQ overall score represents the mean of the following 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. | Baseline, 3, 6,12 and 24 months | 
| Short Form-36 (SF-36) General Health Subscale | SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life. | Baseline, 3, 6, 12 and 24 months | 
| Short Form-36 (SF-36) Mental Health Subscale | SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life. | Baseline, 3, 6, 12 and 24 months | 
| Short Form-36 (SF-36) Social Functioning Subscale | SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life. | Baseline, 3, 6, 12 and 24 months | 
| Short Form-36 (SF-36) Physiological Functioning Subscale | SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life. | Baseline, 3, 6, 12 and 24 months | 
| Short Form-36 (SF-36) Vitality Subscale | SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life. | Baseline, 3, 6, 12 and 24 months | 
| Resource Utilization | Observed Resource Use | 24 months | 
| Resource Utilization Cost | Observed Hospital-Based Cost. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure