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Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure (DEFINE-HF)

Primary Purpose

Chronic Heart Failure With Reduced Systolic Function

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dapagliflozin
Dapagliflozin matching placebo
Sponsored by
Saint Luke's Health System
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Heart Failure With Reduced Systolic Function focused on measuring heart failure, dapagliflozin, Sodium-glucose co-transporter-2 (SGLT-2) inhibitors

Eligibility Criteria

19 Years - 119 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Heart Group of the Eastern Shore
  • University of Southern Califiornia
  • First Coast Cardiovascular Institute
  • Charlotte Heart Group Research Center
  • Emory University
  • NorthShore University HealthSystem Research Institute
  • Northwestern University
  • Advocate Health and Hospitals
  • University of Maryland
  • Walter Reed National Military Medical Center
  • Brigham & Women's Hospital
  • Henry Ford Health System
  • Mayo Clinic
  • Freeman Health System
  • Truman Medical Center
  • Saint Luke's Hospital of Kansas City
  • Washington University
  • New York University
  • St. Francis Hospital
  • Duke University
  • Eastern Nephrology Associates
  • Cleveland Clinic
  • University of Pennsylvania
  • Vanderbilt University
  • University of Texas Southwestern

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dapagliflozin

Dapagliflozin matching placebo

Arm Description

Dapagliflozin 10 mg daily

Dapagliflozin matching placebo 10 mg daily

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Change in Hemoglobin A1c (HbA1c) Over 12 Weeks.
Change in HbA1c over 12 weeks as measured at Week 6 and Week 12.
Change in Weight Over 12 Weeks
Change in weight over 12 weeks as measured at Week 6 and Week 12.
Change in Systolic Blood Pressure Over 12 Weeks
Change in systolic blood pressure over 12 weeks as measured at Week 6 and Week 12.

Full Information

First Posted
January 4, 2016
Last Updated
March 28, 2022
Sponsor
Saint Luke's Health System
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1. Study Identification

Unique Protocol Identification Number
NCT02653482
Brief Title
Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure
Acronym
DEFINE-HF
Official Title
Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
March 3, 2016 (Actual)
Primary Completion Date
June 28, 2019 (Actual)
Study Completion Date
June 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Saint Luke's Health System

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure With Reduced Systolic Function
Keywords
heart failure, dapagliflozin, Sodium-glucose co-transporter-2 (SGLT-2) inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
263 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozin
Arm Type
Active Comparator
Arm Description
Dapagliflozin 10 mg daily
Arm Title
Dapagliflozin matching placebo
Arm Type
Placebo Comparator
Arm Description
Dapagliflozin matching placebo 10 mg daily
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Other Intervention Name(s)
Farxiga
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin matching placebo
Other Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Difference in the Average of the 6- and 12-week Mean N-terminal Pro B-type Natriuretic Peptide (NTproBNP).
Description
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
Title
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
Description
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.
Time Frame
Average of Week 6 and Week 12
Secondary Outcome Measure Information:
Title
Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)
Description
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.
Time Frame
Baseline to Week 6 and Week 12
Title
Percentage of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)
Description
Percentage of patients with a ≥ 20% decrease in NTproBNP as measured at Week 6 and Week 12.
Time Frame
Baseline to Week 6 and Week 12
Title
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)
Description
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.
Time Frame
Average of Week 6 and Week 12
Title
Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) Over 12 Weeks.
Description
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.
Time Frame
Baseline to Week 6 and Week 12
Title
Change in 6 Minute Walk Score Over 12 Weeks.
Description
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.
Time Frame
Baseline to Week 6 and Week 12
Title
Change in Brain Natriuretic Peptide (BNP) Over 12 Weeks.
Description
Change in BNP over 12 weeks as measured at Week 6 and Week 12 as measured at Week 6 and Week 12.
Time Frame
Baseline to Week 6 and Week 12
Title
Change in Hemoglobin A1c (HbA1c) Over 12 Weeks.
Description
Change in HbA1c over 12 weeks as measured at Week 6 and Week 12.
Time Frame
Baseline to Week 6 and Week 12
Title
Change in Weight Over 12 Weeks
Description
Change in weight over 12 weeks as measured at Week 6 and Week 12.
Time Frame
Baseline to Week 6 and Week 12
Title
Change in Systolic Blood Pressure Over 12 Weeks
Description
Change in systolic blood pressure over 12 weeks as measured at Week 6 and Week 12.
Time Frame
Baseline to Week 6 and Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
119 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikhail Kosiborod, MD
Organizational Affiliation
Saint Luke's Mid America Heart Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Heart Group of the Eastern Shore
City
Fairhope
State/Province
Alabama
ZIP/Postal Code
36532
Country
United States
Facility Name
University of Southern Califiornia
City
Los Angeles
State/Province
California
ZIP/Postal Code
90032
Country
United States
Facility Name
First Coast Cardiovascular Institute
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Charlotte Heart Group Research Center
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
NorthShore University HealthSystem Research Institute
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Northwestern University
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60208
Country
United States
Facility Name
Advocate Health and Hospitals
City
Oakbrook Terrace
State/Province
Illinois
ZIP/Postal Code
60181
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Freeman Health System
City
Joplin
State/Province
Missouri
ZIP/Postal Code
64804
Country
United States
Facility Name
Truman Medical Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Saint Luke's Hospital of Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
St. Francis Hospital
City
Roslyn
State/Province
New York
ZIP/Postal Code
11576
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Eastern Nephrology Associates
City
New Bern
State/Province
North Carolina
ZIP/Postal Code
28562
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19106
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31524498
Citation
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.
Results Reference
background
PubMed Identifier
35603596
Citation
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. Erratum In: Circulation. 2022 Sep 13;146(11):e167.
Results Reference
derived
PubMed Identifier
31081589
Citation
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.
Results Reference
derived
Links:
URL
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
Description
Drug information for dapagliflozin

Learn more about this trial

Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure

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