Purpose

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.

Condition

Eligibility

Eligible Ages
Between 19 Years and 119 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
  2. 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
  3. 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
  4. 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
  5. On a diuretic ≥15 days prior to screening visit and a stable diuretic therapy for 7 days
  6. 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

  1. Decompensated heart failure (hospitalization for heart failure within 7 days prior to screening)
  2. History of type 1 diabetes
  3. History of diabetic ketoacidosis
  4. Estimated glomerular filtration rate (eGFR) < 30 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)
  5. 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.
  6. Admission for cardiac resynchronization therapy (CRT) within 90 days prior to the screening visit.
  7. 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.
  8. 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.
  9. History of hypersensitivity to dapagliflozin
  10. For women of child-bearing potential: Current or planned pregnancy or currently lactating.
  11. Life expectancy <1 year at the screening visit
  12. Patients who are volume depleted based upon physical examination at the time of the screening or randomization visit
  13. BNP <75 pg/mL and NTproBNP<225 pg/mL at the screening visit. For patients with permanent atrial fibrillation exclusion thresholds will be BNP<100 pg/mL and NTproBNP<375pg/mL.
  14. Patients currently being treated with any SGLT-2 inhibitor (dapagliflozin, canagliflozin, empagliflozin) or having received treatment with any SGLT-2 inhibitor within the 12 weeks prior to the screening visit.
  15. Average supine systolic BP <100 mmHg at the screening or randomization visit
  16. Past or current history of bladder cancer
  17. Donation of blood or bone marrow 12 weeks prior to the screening visit and no planned donations during the study period
  18. Heart failure due to restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe stenotic valve disease, and HOCM (hypertrophic obstructive cardiomyopathy).
  19. Heart failure due to severe aortic or mitral regurgitation
  20. Severe COPD thought to be a primary contributor to dyspnea
  21. Isolated right heart failure due to pulmonary disease
  22. Active and significant ischemia thought to contribute to dyspnea
  23. Documentation of previous EF < 45%, under stable conditions, within the past 36 months
  24. Complex congenital heart disease
  25. Uncontrolled hypertension, defined as systolic blood pressure ≥200 mmHg during the screening visit (average value of three blood pressure measurements obtained in supine position)
  26. Any other condition that in the judgment of the investigator would jeopardize the patient's participation in the study or that may interfere with the interpretation of study data or if the patient is considered unlikely to comply with study procedures, restrictions and requirements
  27. Bariatric surgery within the past 6 months or planned bariatric surgery within the study time course.
  28. CardioMems device implantation within previous 4 weeks or planned CardioMems implantation during study period
  29. For echo substudy only: patients with ventricular paced rhythm or left bundle branch block on the most recent clinically available 12-lead electrocardiogram.
  30. For echo substudy only: permanent atrial fibrillation

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Dapagliflozin
Dapagliflozin 10 mg oral tablet, once daily, for 12 weeks
  • Drug: Dapagliflozin 10Mg Oral Tablet
    Dapagliflozin 10Mg Oral Tablet
    Other names:
    • Farxiga
Placebo Comparator
Placebo
Dapagliflozin matching placebo oral tablet, once daily, for 12 weeks
  • Drug: Dapagliflozin matching placebo
    Dapagliflozin matching placebo
    Other names:
    • Placebo Oral Tablet

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Study Coordinator
615-343-9071

More Details

NCT ID
NCT03030235
Status
Recruiting
Sponsor
Saint Luke's Health System

Study Contact

Sheryl Windsor
8169329858
PRESERVED-HF@saint-lukes.org

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.