Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure

NCT ID: NCT02653482

Last Updated: 2022-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 263 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-03
• Study Completion Date: 2019-06-28

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.

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 (BNP and NTproBNP), 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dapagliflozin

Dapagliflozin 10 mg daily

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

Dapagliflozin matching placebo

Dapagliflozin matching placebo 10 mg daily

Group Type: PLACEBO_COMPARATOR

Dapagliflozin matching placebo

Intervention Type: DRUG

Interventions

Dapagliflozin

Intervention Type: DRUG

Dapagliflozin matching placebo

Intervention Type: DRUG

Other Intervention Names

Farxiga; Placebo

Eligibility Criteria

Inclusion Criteria

1. 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

2. No change in diuretic management for at least 1 week prior to enrollment

3. Brain natriuretic peptide (BNP) ≥100 pg/mL and/or N-terminal pro b-type natriuretic peptide (NTproBNP) ≥ 400 pg/mL at enrollment

Exclusion Criteria

1. History of type 1 diabetes

2. Estimated glomerular filtration rate (eGFR) < 30 at enrollment

3. Hospitalization for heart failure within the 30 days prior to enrollment

4. 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

5. Admission for cardiac resynchronization therapy (CRT) within 90 days prior to the screening visit

6. 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

7. Patients who are volume depleted based upon physical examination at the time of screening or randomization

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 119 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saint Luke's Health System

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikhail Kosiborod, MD

Role: STUDY_CHAIR

Saint Luke's Mid America Heart Institute

Locations

Heart Group of the Eastern Shore

Fairhope, Alabama, United States

University of Southern Califiornia

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 Institute

Evanston, Illinois, United States

Northwestern University

Evanston, Illinois, United States

Advocate Health and Hospitals

Oakbrook Terrace, Illinois, United States

University of Maryland

Baltimore, Maryland, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Freeman Health System

Joplin, Missouri, United States

Truman Medical Center

Kansas City, Missouri, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Washington University

St Louis, Missouri, United States

New York University

New York, New York, United States

St. Francis Hospital

Roslyn, New York, United States

Duke University

Durham, North Carolina, United States

Eastern Nephrology Associates

New Bern, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 31524498 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39421941 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37203441 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35603596 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31081589 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=0461432268&QV1=DAPAGLIFLOZIN

Drug information for dapagliflozin

Other Identifiers

D1690C00032

Identifier Type: -

Identifier Source: org_study_id