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Chronic Heart Failure With Reduced Systolic FunctionPhase 4DEFINE-HFNCT02653482

Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure

A Phase 4 study testing Dapagliflozin in people with Chronic Heart Failure With Reduced Systolic Function, run by Saint Luke's Health System at 25 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 to 119 years
What is being tested?
Dapagliflozin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
263 participants
Where
25 sitesUnited States
Study dates
3 Mar 2016to 28 Jun 2019
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 119 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites
  • Emory University

    Atlanta, Georgia, 30303

  • University of Maryland

    Baltimore, Maryland, 21201

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University

    Durham, North Carolina, 27705

  • NorthShore University HealthSystem Research Institute

    Evanston, Illinois, 60201

  • Northwestern University

    Evanston, Illinois, 60208

  • Heart Group of the Eastern Shore

    Fairhope, Alabama, 36532

  • First Coast Cardiovascular Institute

    Jacksonville, Florida, 32256

  • Freeman Health System

    Joplin, Missouri, 64804

  • Truman Medical Center

    Kansas City, Missouri, 64108

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • University of Southern Califiornia

    Los Angeles, California, 90032

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Eastern Nephrology Associates

    New Bern, North Carolina, 28562

  • New York University

    New York, New York, 10016

  • Advocate Health and Hospitals

    Oakbrook Terrace, Illinois, 60181

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19106

  • Charlotte Heart Group Research Center

    Port Charlotte, Florida, 33952

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • St. Francis Hospital

    Roslyn, New York, 11576

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

About this study

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.

Read the 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.

Being tested
Dapagliflozin, Dapagliflozin matching placebo
Keywords
heart failure, dapagliflozin, Sodium-glucose co-transporter-2 (SGLT-2) inhibitors
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DapagliflozinDrug

    Also called Farxiga

  • Dapagliflozin matching placeboDrug

    Also called Placebo

Study groups in NCT02653482
Study groupRoleWhat they receive
DapagliflozinActive comparatorDapagliflozin 10 mg daily
Receives: Drug: Dapagliflozin
Dapagliflozin matching placeboPlacebo comparatorDapagliflozin matching placebo 10 mg daily
Receives: Drug: Dapagliflozin matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Average of Week 6 and Week 12

  2. 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.

    Measured: Average of Week 6 and Week 12

Secondary outcomes (9)
  1. Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)

    Percentage of patients with a ≥ 5-point increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) as measured at Week 6 and 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 overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points.

    Measured: Baseline to Week 6 and Week 12

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

    Percentage of patients with a ≥ 20% decrease in NTproBNP as measured at Week 6 and Week 12.

    Measured: Baseline to Week 6 and Week 12

  3. 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)

    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.

    Measured: Average of Week 6 and Week 12

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

    Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) over 12 weeks as measured at Week 6 and 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 overall summary score, a small but clinically meaningful change is considered to be ≥ 5 points.

    Measured: Baseline to Week 6 and Week 12

  5. Change in 6 Minute Walk Score Over 12 Weeks.

    Change in 6 minute walk score over 12 weeks as measured at Week 6 and Week 12. The 6 minute walk test measures the distance in meters that a patient can quickly walk on a flat, hard surface in a period of 6 minutes.

    Measured: Baseline to Week 6 and Week 12

  6. Change in Brain Natriuretic Peptide (BNP) Over 12 Weeks.

    Change in BNP over 12 weeks as measured at Week 6 and Week 12 as measured at Week 6 and Week 12.

    Measured: Baseline to Week 6 and Week 12

  7. Change in Hemoglobin A1c (HbA1c) Over 12 Weeks.

    Change in HbA1c over 12 weeks as measured at Week 6 and Week 12.

    Measured: Baseline to Week 6 and Week 12

  8. Change in Weight Over 12 Weeks

    Change in weight over 12 weeks as measured at Week 6 and Week 12.

    Measured: Baseline to Week 6 and Week 12

  9. Change in Systolic Blood Pressure Over 12 Weeks

    Change in systolic blood pressure over 12 weeks as measured at Week 6 and Week 12.

    Measured: Baseline to Week 6 and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2016 (estimated)
  2. Study start3 Mar 2016
  3. Primary completion28 Jun 2019
  4. Study completion28 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
263 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02653482
Sponsor's protocol ID
D1690C00032
Acronym
DEFINE-HF
Status last verified
Mar 2022
First submitted
4 Jan 2016
Last updated
21 Apr 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 31524498
  • 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.

    PubMed 39421941
  • 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.

    PubMed 37203441
  • 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.

    PubMed 35603596
  • 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.

    PubMed 31081589

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dapagliflozin in people with Chronic Heart Failure With Reduced Systolic Function, run by Saint Luke's Health System at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in the Average of the 6- and 12-week Mean N-terminal Pro B-type Natriuretic Peptide (NTproBNP). (time frame: Average of Week 6 and Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02653482, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2022.

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