Dapagliflozin in PRESERVED Ejection Fraction Heart Failure

NCT03030235 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: D1690C00053
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 26

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.

Conditions

Chronic Heart Failure With Preserved Systolic Function

Keywords

heart failure; dapagliflozin; SGLT-2 inhibitors

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Baseline to Week 12

Secondary Outcomes (10)

• 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 Brain Natriuretic Peptide (BNP)

  Baseline to Week 12

• 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 Hemoglobin A1c

  Baseline to Week 12

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Dapagliflozin 10 mg oral tablet, once daily, for 12 weeks

Drug: Dapagliflozin 10Mg Oral Tablet

Placebo

PLACEBO COMPARATOR

Dapagliflozin matching placebo oral tablet, once daily, for 12 weeks

Drug: Dapagliflozin matching placebo

Interventions

Dapagliflozin 10Mg Oral Tablet DRUG

Dapagliflozin 10Mg Oral Tablet

Also known as: Farxiga

Dapagliflozin

Dapagliflozin matching placebo DRUG

Dapagliflozin matching placebo

Also known as: Placebo Oral Tablet

Placebo

Eligibility Criteria

• Age: 19 Years - 119 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• Life expectancy \<1 year at the screening visit
• Patients who are volume depleted based upon physical examination at the time of the screening or randomization visit
• 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.
• Average supine systolic BP \<100 mmHg at the screening or randomization visit
• Current history of bladder cancer

Sponsors & Collaborators

• Saint Luke's Health System: lead

Study Sites (26)

Heart Group of the Eastern Shore

Fairhope, Alabama, 36532, United States

Location

University of Southern California

Los Angeles, California, 90032, United States

Location

First Coast Cardiovascular Institute

Jacksonville, Florida, 32256, United States

Location

Charlotte Heart Group Research Center

Port Charlotte, Florida, 33952, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

NorthShore University HealthSystem Research Insititute

Evanston, Illinois, 60201, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Chicago Medical Research

Hazel Crest, Illinois, 60429, United States

Location

OSF HealthCare Cardiovascular Institute

Peoria, Illinois, 61606, United States

Location

St. Vincent Cardiovascular Research Institute

Indianapolis, Indiana, 46260, United States

Location

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Massachusetts Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Mid America Heart Institute

Kansas City, Missouri, 64111, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

St. Francis Hospital

New York, New York, 11576, United States

Location

Eastern Nephrology Associates

New Bern, North Carolina, 28562, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Allegheny Health Network Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor Scott and White Research Institute

Dallas, Texas, 75204, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23501, United States

Location

Related Publications (6)

• 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.

  PMID: 34711976 RESULT

• 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.

  PMID: 39421941 DERIVED

• 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.

  PMID: 38639697 DERIVED

• 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.

  PMID: 37869881 DERIVED

• 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.

  PMID: 37203441 DERIVED

• 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.

  PMID: 31081589 DERIVED

Related Links

• Dapagliflozin information

MeSH Terms

Conditions

Heart Failure

Interventions

dapagliflozin; Tablets

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: PRESERVED-HF Study Manager
• Organization: Saint Luke's Hospital of Kansas City

PRESERVED-HF@saint-lukes.org

816-932-9858

Study Officials

• Mikhail Kosiborod, MD

  Saint Luke's Mid America Heart Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: March 1, 2017
• Primary Completion: August 13, 2021
• Study Completion: August 13, 2021
• Last Updated: October 19, 2022
• Results First Posted: October 19, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (26)