Chronic Heart Failure With Reduced Systolic Function Clinical Trial
— DEFINE-HFOfficial title:
Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure
| Verified date | March 2022 |
| Source | Saint Luke's Health System |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 263 |
| Est. completion date | June 28, 2019 |
| Est. primary completion date | June 28, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 19 Years to 119 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Emory University | Atlanta | Georgia |
| 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 | Cleveland Clinic | Cleveland | Ohio |
| United States | University of Texas Southwestern | Dallas | Texas |
| United States | Henry Ford Health System | Detroit | Michigan |
| United States | Duke University | Durham | North Carolina |
| United States | NorthShore University HealthSystem Research Institute | Evanston | Illinois |
| United States | Northwestern University | Evanston | Illinois |
| United States | Heart Group of the Eastern Shore | Fairhope | Alabama |
| United States | First Coast Cardiovascular Institute | Jacksonville | Florida |
| United States | Freeman Health System | Joplin | Missouri |
| United States | Saint Luke's Hospital of Kansas City | Kansas City | Missouri |
| United States | Truman Medical Center | Kansas City | Missouri |
| United States | University of Southern Califiornia | Los Angeles | California |
| United States | Vanderbilt University | Nashville | Tennessee |
| United States | Eastern Nephrology Associates | New Bern | North Carolina |
| United States | New York University | New York | New York |
| United States | Advocate Health and Hospitals | Oakbrook Terrace | Illinois |
| United States | University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Charlotte Heart Group Research Center | Port Charlotte | Florida |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | St. Francis Hospital | Roslyn | New York |
| United States | Washington University | Saint Louis | Missouri |
| Lead Sponsor | Collaborator |
|---|---|
| Saint Luke's Health System |
United States,
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | 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. |
Baseline to Week 6 and Week 12 | |
| Secondary | 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. | Baseline to Week 6 and Week 12 | |
| Secondary | 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. | Average of Week 6 and Week 12 | |
| Secondary | 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. | Baseline to Week 6 and Week 12 | |
| Secondary | 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. | Baseline to Week 6 and Week 12 | |
| Secondary | 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. | Baseline to Week 6 and Week 12 | |
| Secondary | Change in Hemoglobin A1c (HbA1c) Over 12 Weeks. | Change in HbA1c over 12 weeks as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | |
| Secondary | Change in Weight Over 12 Weeks | Change in weight over 12 weeks as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 | |
| Secondary | Change in Systolic Blood Pressure Over 12 Weeks | Change in systolic blood pressure over 12 weeks as measured at Week 6 and Week 12. | Baseline to Week 6 and Week 12 |