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

March 28, 2022 updated by: Saint Luke's Health System
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

263

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Fairhope, Alabama, United States, 36532
        • Heart Group of the Eastern Shore
    • California
      • Los Angeles, California, United States, 90032
        • University of Southern Califiornia
    • Florida
      • Jacksonville, Florida, United States, 32256
        • First Coast Cardiovascular Institute
      • Port Charlotte, Florida, United States, 33952
        • Charlotte Heart Group Research Center
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory University
    • Illinois
      • Evanston, Illinois, United States, 60208
        • Northwestern University
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem Research Institute
      • Oakbrook Terrace, Illinois, United States, 60181
        • Advocate Health and Hospitals
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham & Women's Hospital
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Joplin, Missouri, United States, 64804
        • Freeman Health System
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Center
      • Saint Louis, Missouri, United States, 63110
        • Washington University
    • New York
      • New York, New York, United States, 10016
        • New York University
      • Roslyn, New York, United States, 11576
        • St. Francis Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University
      • New Bern, North Carolina, United States, 28562
        • Eastern Nephrology Associates
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 119 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dapagliflozin
Dapagliflozin 10 mg daily
Drug: Dapagliflozin
Other Names:
  • Farxiga
Placebo Comparator: Dapagliflozin matching placebo
Dapagliflozin matching placebo 10 mg daily
Drug: Dapagliflozin matching placebo
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Time Frame: Average of Week 6 and Week 12

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)
Time Frame: 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) 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.
Baseline to Week 6 and Week 12
Percentage of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)
Time Frame: Baseline to Week 6 and Week 12
Percentage of patients with a ≥ 20% decrease in NTproBNP as measured at Week 6 and Week 12.
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)
Time Frame: Average of 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.
Average of Week 6 and Week 12
Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) Over 12 Weeks.
Time Frame: Baseline to Week 6 and Week 12
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.
Baseline to Week 6 and Week 12
Change in 6 Minute Walk Score Over 12 Weeks.
Time Frame: Baseline to Week 6 and Week 12
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.
Baseline to Week 6 and Week 12
Change in Brain Natriuretic Peptide (BNP) Over 12 Weeks.
Time Frame: Baseline to Week 6 and Week 12
Change in BNP over 12 weeks as measured at Week 6 and Week 12 as measured at Week 6 and Week 12.
Baseline to Week 6 and Week 12
Change in Hemoglobin A1c (HbA1c) Over 12 Weeks.
Time Frame: Baseline to Week 6 and Week 12
Change in HbA1c over 12 weeks as measured at Week 6 and Week 12.
Baseline to Week 6 and Week 12
Change in Weight Over 12 Weeks
Time Frame: Baseline to Week 6 and Week 12
Change in weight over 12 weeks as measured at Week 6 and Week 12.
Baseline to Week 6 and Week 12
Change in Systolic Blood Pressure Over 12 Weeks
Time Frame: Baseline to Week 6 and Week 12
Change in systolic blood pressure over 12 weeks as measured at Week 6 and Week 12.
Baseline to Week 6 and Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Saint Luke's Health System

Investigators

  • Study Chair: Mikhail Kosiborod, MD, Saint Luke's Mid America Heart Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2016

Primary Completion (Actual)

June 28, 2019

Study Completion (Actual)

June 28, 2019

Study Registration Dates

First Submitted

January 4, 2016

First Submitted That Met QC Criteria

January 9, 2016

First Posted (Estimate)

January 12, 2016

Study Record Updates

Last Update Posted (Actual)

April 21, 2022

Last Update Submitted That Met QC Criteria

March 28, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D1690C00032

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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