Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the impact of dapagliflozin, as compared with placebo, on heart failure disease-specific biomarkers, symptoms, health status, and quality of life in patients with chronic heart failure with reduced systolic function.

Detailed Description
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A 12-week randomized, double-blind, placebo-controlled trial to evaluate the effects of once-daily dapagliflozin 10 mg on heart failure disease-specific biomarkers (BNP and NTproBNP), symptoms, health status, and quality of life in patients with chronic heart failure with reduced systolic function.

Official Title
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Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure

Conditions
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Chronic Heart Failure With Reduced Systolic Function

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Dapagliflozin matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of New York Heart Association (NYHA) Class II or Class III heart failure (left ventricular ejection fraction ≤40% due to either ischemic or non-ischemic etiology) with reduced systolic function for at least 16 weeks prior to enrollment No change in diuretic management for at least 1 week prior to enrollment Brain natriuretic peptide (BNP) ≥100 pg/mL and/or N-terminal pro b-type natriuretic peptide (NTproBNP) ≥ 400 pg/mL at enrollment Exclusion Criteria: History of type 1 diabetes Estimated glomerular filtration rate (eGFR) < 30 at enrollment Hospitalization for heart failure within the 30 days prior to enrollment Admission for an acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina), percutaneous coronary intervention, or cardiac surgery within the 30 days prior to enrollment Admission for cardiac resynchronization therapy (CRT) within 90 days prior to the screening visit Planned cardiovascular revascularization (percutaneous intervention or surgical) or major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy) within the 90 days after enrollment Patients who are volume depleted based upon physical examination at the time of screening or randomization

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 119 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin<br>Dapagliflozin 10 mg daily | Drug: Dapagliflozin<br> <br> * Other names: Farxiga;|
| Placebo Comparator: Dapagliflozin matching placebo<br>Dapagliflozin matching placebo 10 mg daily | Drug: Dapagliflozin matching placebo<br> <br> * Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the Average of the 6- and 12-week Mean N-terminal Pro B-type Natriuretic Peptide (NTproBNP). | Difference in the average of the 6- and 12-week mean N-terminal pro B-type natriuretic peptide (NTproBNP). | Average of Week 6 and Week 12 | 
| Percentage of Patients That Achieve a ≥ 5-point Increase in Heart Failure Disease Specific Quality of Life (Assessed Using Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)) or a ≥ 20% Decrease in NTproBNP Over 12 Weeks | A composite of the percentage of patients that achieved a meaningful improvement in health status (≥5-point increase in average of 6- and 12-week KCCQ-OS) or NT-proBNP (≥20% decrease in average of 6- and 12-week NT-proBNP). The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points. | Average of Week 6 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) | Percentage of patients with a ≥ 5-point increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) as measured at Week 6 and Week 12. The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points. | Baseline to Week 6 and Week 12 | 
| Percentage of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP) | Percentage of patients with a ≥ 20% decrease in NTproBNP as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | 
| Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OS) and a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP) | The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points. | Average of Week 6 and Week 12 | 
| Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) Over 12 Weeks. | Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) over 12 weeks as measured at Week 6 and Week 12.The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points. | Baseline to Week 6 and Week 12 | 
| Change in 6 Minute Walk Score Over 12 Weeks. | Change in 6 minute walk score over 12 weeks as measured at Week 6 and Week 12. The 6 minute walk test measures the distance in meters that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. | Baseline to Week 6 and Week 12 | 
| Change in Brain Natriuretic Peptide (BNP) Over 12 Weeks. | Change in BNP over 12 weeks as measured at Week 6 and Week 12 as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | 
| Change in Hemoglobin A1c (HbA1c) Over 12 Weeks. | Change in HbA1c over 12 weeks as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | 
| Change in Weight Over 12 Weeks | Change in weight over 12 weeks as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | 
| Change in Systolic Blood Pressure Over 12 Weeks | Change in systolic blood pressure over 12 weeks as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure, dapagliflozin, Sodium-glucose co-transporter-2 (SGLT-2) inhibitors