Dapagliflozin in PRESERVED Ejection Fraction Heart Failure
NCT ID: NCT03030235
Last Updated: 2022-10-19
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
324 participants
INTERVENTIONAL
2017-03-01
2021-08-13
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Dapagliflozin
Dapagliflozin 10 mg oral tablet, once daily, for 12 weeks
Dapagliflozin 10Mg Oral Tablet
Dapagliflozin 10Mg Oral Tablet
Placebo
Dapagliflozin matching placebo oral tablet, once daily, for 12 weeks
Dapagliflozin matching placebo
Dapagliflozin matching placebo
Interventions
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Dapagliflozin 10Mg Oral Tablet
Dapagliflozin 10Mg Oral Tablet
Dapagliflozin matching placebo
Dapagliflozin matching placebo
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
2. History of type 1 diabetes
3. History of diabetic ketoacidosis
4. 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)
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, ertugliflozin) 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. 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 be a primary contributor 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
19 Years
119 Years
ALL
No
Sponsors
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Saint Luke's Health System
OTHER
Responsible Party
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Principal Investigators
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Mikhail Kosiborod, MD
Role: STUDY_CHAIR
Saint Luke's Mid America Heart Institute
Locations
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Heart Group of the Eastern Shore
Fairhope, Alabama, United States
University of Southern California
Los Angeles, California, United States
First Coast Cardiovascular Institute
Jacksonville, Florida, United States
Charlotte Heart Group Research Center
Port Charlotte, Florida, United States
Emory University
Atlanta, Georgia, United States
NorthShore University HealthSystem Research Insititute
Evanston, Illinois, United States
Northwestern University
Evanston, Illinois, United States
Chicago Medical Research
Hazel Crest, Illinois, United States
OSF HealthCare Cardiovascular Institute
Peoria, Illinois, United States
St. Vincent Cardiovascular Research Institute
Indianapolis, Indiana, United States
Cotton O'Neil Clinical Research Center
Topeka, Kansas, United States
Johns Hopkins University
Baltimore, Maryland, United States
Massachusetts Hospital
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Saint Luke's Mid America Heart Institute
Kansas City, Missouri, United States
Washington University
St Louis, Missouri, United States
Columbia University
New York, New York, United States
St. Francis Hospital
New York, New York, United States
Eastern Nephrology Associates
New Bern, North Carolina, United States
Wake Forest University
Winston-Salem, North Carolina, United States
Oregon Health and Science University
Portland, Oregon, United States
Allegheny Health Network Research Institute
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor Scott and White Research Institute
Dallas, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Eastern Virginia Medical School
Norfolk, Virginia, United States
Countries
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References
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Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, Khariton Y, Malik AO, Khumri T, Umpierrez G, Lamba S, Sharma K, Khan SS, Chandra L, Gordon RA, Ryan JJ, Chaudhry SP, Joseph SM, Chow CH, Kanwar MK, Pursley M, Siraj ES, Lewis GD, Clemson BS, Fong M, Kosiborod MN. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021 Nov;27(11):1954-1960. doi: 10.1038/s41591-021-01536-x. Epub 2021 Oct 28.
Selvaraj S, Patel S, Sauer AJ, McGarrah RW, Jones P, Kwee LC, Windsor SL, Ilkayeva O, Muehlbauer MJ, Newgard CB, Borlaug BA, Kitzman DW, Shah SJ, Margulies KB, Husain M, Inzucchi SE, McGuire DK, Lanfear DE, Javaheri A, Umpierrez G, Mentz RJ, Sharma K, Kosiborod MN, Shah SH. Metabolic Effects of the SGLT2 Inhibitor Dapagliflozin in Heart Failure Across the Spectrum of Ejection Fraction. Circ Heart Fail. 2024 Nov;17(11):e011980. doi: 10.1161/CIRCHEARTFAILURE.124.011980. Epub 2024 Oct 18.
Selvaraj S, Patel S, Sauer AJ, McGarrah RW, Jones P, Kwee LC, Windsor SL, Ilkayeva O, Muehlbauer MJ, Newgard CB, Borlaug BA, Kitzman DW, Shah SJ, Shah SH, Kosiborod MN; PRESERVED-HF Investigators. Targeted Metabolomic Profiling of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The PRESERVED-HF Trial. JACC Heart Fail. 2024 Jun;12(6):999-1011. doi: 10.1016/j.jchf.2024.02.018. Epub 2024 Apr 17.
Lewis GD, Gosch K, Cohen LP, Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Khumri T, Umpierrez G, Lamba S, Sharma K, Khan SS, Kosiborod MN, Sauer AJ. Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF. Circ Heart Fail. 2023 Nov;16(11):e010633. doi: 10.1161/CIRCHEARTFAILURE.123.010633. Epub 2023 Oct 23.
Nassif ME, Windsor SL, Gosch K, Borlaug BA, Husain M, Inzucchi SE, Kitzman DW, McGuire DK, Pitt B, Scirica BM, Shah SJ, Umpierrez G, Austin BA, Lamba S, Khumri T, Sharma K, Kosiborod MN. Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials. Circ Heart Fail. 2023 Jul;16(7):e009837. doi: 10.1161/CIRCHEARTFAILURE.122.009837. Epub 2023 May 19.
Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Dapagliflozin information
Other Identifiers
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D1690C00053
Identifier Type: -
Identifier Source: org_study_id
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