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Dapagliflozin in PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)

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ClinicalTrials.gov Identifier: NCT03030235
Recruitment Status : Recruiting
First Posted : January 24, 2017
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Saint Luke's Health System

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.

Condition or disease Intervention/treatment Phase
Chronic Heart Failure With Preserved Systolic Function Drug: Dapagliflozin 10Mg Oral Tablet Drug: Dapagliflozin matching placebo Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With PRESERVED Ejection Fraction Heart Failure
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Dapagliflozin
Dapagliflozin 10 mg oral tablet, once daily, for 12 weeks
Drug: Dapagliflozin 10Mg Oral Tablet
Dapagliflozin 10Mg Oral Tablet
Other Name: Farxiga

Placebo Comparator: Placebo
Dapagliflozin matching placebo oral tablet, once daily, for 12 weeks
Drug: Dapagliflozin matching placebo
Dapagliflozin matching placebo
Other Name: Placebo Oral Tablet




Primary Outcome Measures :
  1. Change from baseline in NTproBNP at 6 and 12 weeks [ Time Frame: Baseline to Week 6 and Week 12 ]
    Change from baseline in NTproBNP at 6 and 12 weeks


Secondary Outcome Measures :
  1. Change from baseline in heart failure related quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score over the treatment period [ Time Frame: Baseline to Week 12 ]
    Change from baseline in heart failure related quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score over the treatment period

  2. Change from baseline in 6 minute walk test over the treatment period [ Time Frame: Baseline to Week 12 ]
    Change from baseline in 6 minute walk test over the treatment period

  3. Change from baseline in BNP over the treatment period [ Time Frame: Baseline to Week 12 ]
    Change from baseline in BNP over the treatment period

  4. Change from baseline in HbA1c over the treatment period (evaluated separately in patients with and without type 2 diabetes) [ Time Frame: Baseline to Week 12 ]
    Change from baseline in HbA1c over the treatment period (evaluated separately in patients with and without type 2 diabetes)

  5. Proportion of patients with a ≥ 5pts increase in KCCQ [ Time Frame: Baseline to Week 12 ]
    Proportion of patients with a ≥ 5pts increase in KCCQ

  6. Proportion of patients with a ≥ 20% decrease in NTproBNP [ Time Frame: Baseline to Week 12 ]
    Proportion of patients with a ≥ 20% decrease in NTproBNP

  7. Proportion of patients with a ≥ 5pts increase in KCCQ and a ≥ 20% decrease in NTproBNP [ Time Frame: Baseline to Week 12 ]
    Proportion of patients with a ≥ 5pts increase in KCCQ and a ≥ 20% decrease in NTproBNP

  8. Change in weight over 12 weeks [ Time Frame: Baseline to Week 12 ]
    Change in weight over 12 weeks

  9. Change in systolic blood pressure over 12 weeks [ Time Frame: Baseline to Week 12 ]
    Change in systolic blood pressure over 12 weeks



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Ages Eligible for Study:   19 Years to 119 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030235


Contacts
Contact: Sheryl Windsor 8169329858 PRESERVED-HF@saint-lukes.org

  Show 24 Study Locations
Sponsors and Collaborators
Saint Luke's Health System
Investigators
Study Chair: Mikhail Kosiborod, MD Saint Luke's Mid America Heart Institute

Additional Information:
Responsible Party: Saint Luke's Health System
ClinicalTrials.gov Identifier: NCT03030235     History of Changes
Other Study ID Numbers: D1690C00053
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Saint Luke's Health System:
heart failure
dapagliflozin
SGLT-2 inhibitors

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases