Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure

NCT02653482 | Completed Phase 4 Results DMC

• 1 other identifier: D1690C00032
• Study Type: interventional
• Target: 263
• Locations: 1 country
• Sites: 25

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 reduced systolic function.

Conditions

Chronic Heart Failure With Reduced Systolic Function

Keywords

heart failure; dapagliflozin; Sodium-glucose co-transporter-2 (SGLT-2) inhibitors

Outcome Measures

Primary Outcomes (2)

• Difference in the Average of the 6- and 12-week Mean N-terminal Pro B-type Natriuretic Peptide (NTproBNP).

  Difference in the average of the 6- and 12-week mean N-terminal pro B-type natriuretic peptide (NTproBNP).

  Average of Week 6 and Week 12

• Percentage of Patients That Achieve a ≥ 5-point Increase in Heart Failure Disease Specific Quality of Life (Assessed Using Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)) or a ≥ 20% Decrease in NTproBNP Over 12 Weeks

  A composite of the percentage of patients that achieved a meaningful improvement in health status (≥5-point increase in average of 6- and 12-week KCCQ-OS) or NT-proBNP (≥20% decrease in average of 6- and 12-week NT-proBNP). 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 overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points.

  Average of Week 6 and Week 12

Secondary Outcomes (9)

• Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)

  Baseline to Week 6 and Week 12

• Percentage of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)

  Baseline to Week 6 and Week 12

• Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OS) and a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)

  Average of Week 6 and Week 12

• Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) Over 12 Weeks.

  Baseline to Week 6 and Week 12

• Change in 6 Minute Walk Score Over 12 Weeks.

  Baseline to Week 6 and Week 12

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Dapagliflozin 10 mg daily

Drug: Dapagliflozin

Dapagliflozin matching placebo

PLACEBO COMPARATOR

Dapagliflozin matching placebo 10 mg daily

Drug: Dapagliflozin matching placebo

Interventions

Dapagliflozin DRUG

Also known as: Farxiga

Dapagliflozin

Dapagliflozin matching placebo DRUG

Also known as: Placebo

Dapagliflozin matching 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:

• Established diagnosis of New York Heart Association (NYHA) Class II or Class III heart failure (left ventricular ejection fraction ≤40% due to either ischemic or non-ischemic etiology) with reduced systolic function for at least 16 weeks prior to enrollment
• No change in diuretic management for at least 1 week prior to enrollment
• Brain natriuretic peptide (BNP) ≥100 pg/mL and/or N-terminal pro b-type natriuretic peptide (NTproBNP) ≥ 400 pg/mL at enrollment

You may not qualify if:

• History of type 1 diabetes
• Estimated glomerular filtration rate (eGFR) \< 30 at enrollment
• Hospitalization for heart failure within the 30 days prior to enrollment
• Admission for an acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina), percutaneous coronary intervention, or cardiac surgery within the 30 days prior to enrollment
• 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) within the 90 days after enrollment
• Patients who are volume depleted based upon physical examination at the time of screening or randomization

Sponsors & Collaborators

• Saint Luke's Health System: lead

Study Sites (25)

Heart Group of the Eastern Shore

Fairhope, Alabama, 36532, United States

Location

University of Southern Califiornia

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 Institute

Evanston, Illinois, 60201, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Advocate Health and Hospitals

Oakbrook Terrace, Illinois, 60181, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Freeman Health System

Joplin, Missouri, 64804, United States

Location

Truman Medical Center

Kansas City, Missouri, 64108, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

New York University

New York, New York, 10016, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Eastern Nephrology Associates

New Bern, North Carolina, 28562, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19106, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Related Publications (5)

• Nassif ME, Windsor SL, Tang F, Khariton Y, Husain M, Inzucchi SE, McGuire DK, Pitt B, Scirica BM, Austin B, Drazner MH, Fong MW, Givertz MM, Gordon RA, Jermyn R, Katz SD, Lamba S, Lanfear DE, LaRue SJ, Lindenfeld J, Malone M, Margulies K, Mentz RJ, Mutharasan RK, Pursley M, Umpierrez G, Kosiborod M. Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial. Circulation. 2019 Oct 29;140(18):1463-1476. doi: 10.1161/CIRCULATIONAHA.119.042929. Epub 2019 Sep 16.

  PMID: 31524498 BACKGROUND

• 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

• 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

• Selvaraj S, Fu Z, Jones P, Kwee LC, Windsor SL, Ilkayeva O, Newgard CB, Margulies KB, Husain M, Inzucchi SE, McGuire DK, Pitt B, Scirica BM, Lanfear DE, Nassif ME, Javaheri A, Mentz RJ, Kosiborod MN, Shah SH; DEFINE-HF Investigators. Metabolomic Profiling of the Effects of Dapagliflozin in Heart Failure With Reduced Ejection Fraction: DEFINE-HF. Circulation. 2022 Sep 13;146(11):808-818. doi: 10.1161/CIRCULATIONAHA.122.060402. Epub 2022 May 23.

  PMID: 35603596 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

• Drug information for dapagliflozin

MeSH Terms

Conditions

Heart Failure

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Program Manager, Cardiometabolic Research
• Organization: Saint Luke's Hospital of Kansas City

DEFINE-HF@saint-lukes.org

8166957561

Study Officials

• Mikhail Kosiborod, MD

  Saint Luke's Mid America Heart Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• 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 4, 2016
• First Posted: January 12, 2016
• Study Start: March 3, 2016
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: April 21, 2022
• Results First Posted: December 1, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)