Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With PRESERVED Ejection Fraction Heart Failure
Overview
- Phase
- Phase 4
- Intervention
- Dapagliflozin 10Mg Oral Tablet
- Conditions
- Chronic Heart Failure With Preserved Systolic Function
- Sponsor
- Saint Luke's Health System
- Enrollment
- 324
- Locations
- 26
- Primary Endpoint
- Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Summary Score (KCCQ-CS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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 preserved systolic function.
Detailed Description
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 (NTproBNP and BNP), symptoms, health status, and quality of life in patients with chronic heart failure with preserved systolic function. An imaging substudy will also be conducted to explore the effects of dapagliflozin vs. placebo on various echocardiographic parameters.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
- •Ejection fraction (EF) ≥ 45% as determined on imaging study within 24 months of enrolment with no change in clinical status suggesting potential for deterioration in systolic function
- •Elevated NT-proBNP (≥ 225 pg/ml) or BNP (≥ 75 pg/ml). For patients with permanent atrial fibrillation inclusion thresholds will be BNP ≥ 100 pg/mL or NTproBNP ≥ 375 pg/mL
- •Stable medical therapy for heart failure for 15 days as defined by: i. No addition or removal of ACE, angiotensin receptor blockers (ARBs), valsartan/sacubitril, beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists; ii.No substantial change in dosage (100% or greater increase or decrease from baseline dose) of ACE, ARBs, beta-blockers, CCBs or aldosterone antagonists
- •On a diuretic ≥15 days prior to screening visit and a stable diuretic therapy for 7 days
- •At least one of the following: i. Hospitalization for decompensated HF in the last 12 months; ii. Acute treatment for HF with intravenous loop diuretic or hemofiltration in the last 12 months; iii. Mean pulmonary capillary wedge pressure ≥15 mmHg or LV end diastolic pressure (LVEDP) ≥15 mmHg documented during catheterization at rest, or pulmonary capillary wedge pressure or LVEDP ≥25 mmHg documented during catheterization with exercise; iv. Structural heart disease evidenced by at least one of the following echo findings (any local measurement made within the 24 months prior to screening visit): a) left atrial (LA) enlargement defined by at least one of the following: LA width ≥3.8cm or LA length ≥5.0 cm or LA area ≥20 cm2 or LA volume ≥55 mL or LA volume index ≥29 mL/m2 b) or left ventricular hypertrophy (LVH) defined by septal thickness or posterior wall thickness ≥1.1 cm.
Exclusion Criteria
- •Decompensated heart failure (hospitalization for heart failure within 7 days prior to screening)
- •History of type 1 diabetes
- •History of diabetic ketoacidosis
- •Estimated glomerular filtration rate (eGFR) \< 20 at the screening visit by modified MDRD equation GFR (mL/min/1.73 m2 ) = 175 x (Scr) -1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American)
- •Admission for an acute coronary syndrome (ST-elevation MI, non-ST-elevation MI, or unstable angina), percutaneous coronary intervention, or cardiac surgery within 30 days prior to the screening visit.
- •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, or transcatheter aortic valve replacement) or CRT within the 90 days after the screening visit.
- •Participation in any interventional clinical trial (with an investigational drug or device) that is not an observational registry within 15 days of the screening visit.
- •History of hypersensitivity to dapagliflozin
- •For women of child-bearing potential: Current or planned pregnancy or currently lactating.
Arms & Interventions
Dapagliflozin
Dapagliflozin 10 mg oral tablet, once daily, for 12 weeks
Intervention: Dapagliflozin 10Mg Oral Tablet
Placebo
Dapagliflozin matching placebo oral tablet, once daily, for 12 weeks
Intervention: Dapagliflozin matching placebo
Outcomes
Primary Outcomes
Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Summary Score (KCCQ-CS)
Time Frame: Baseline to Week 12
Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CS) at 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-CS, a small but clinically meaningful change is considered to be ≥ 5 points. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.
Secondary Outcomes
- Effect of Dapagliflozin, as Compared With Placebo, on 6 Minute Walk Test Distance(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Brain Natriuretic Peptide (BNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Proportion of Patients With ≥ 5 Point Increase in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) and ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide(NTproBNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Weight(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Hemoglobin A1c(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on the Proportion of Patients With a ≥ 5 Point Increase in KCCQ Clinical Summary Score (KCCQ-CS) and KCCQ Overall Summary Score (KCCQ-OS)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on N-terminal Pro B-type Natriuretic Peptide (NTproBNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on the Proportion of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Systolic Blood Pressure(Baseline to Week 12)