Clinical trial NCT02653482: Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure
Official title: Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Heart Failure With Reduced Systolic Function
Keywords: heart failure
dapagliflozin
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors
Lead sponsor: Saint Luke's Health System
Sponsor class: OTHER
First posted: 2016-01-12
Enrollment: 263
Sex: ALL
Minimum age (years): 19
Maximum age (years): 119
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Difference in the Average of the 6- and 12-week Mean N-terminal Pro B-type Natriuretic Peptide (NTproBNP).
timeFrame: Average of Week 6 and Week 12
measure: 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
timeFrame: Average of Week 6 and Week 12
Secondary outcomes:
measure: Percentage of Patients With a ≥ 5-point Increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)
timeFrame: Baseline to Week 6 and Week 12
measure: Percentage of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)
timeFrame: Baseline to Week 6 and Week 12
measure: 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)
timeFrame: Average of Week 6 and Week 12
measure: Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) Over 12 Weeks.
timeFrame: Baseline to Week 6 and Week 12
measure: Change in 6 Minute Walk Score Over 12 Weeks.
timeFrame: Baseline to Week 6 and Week 12
measure: Change in Brain Natriuretic Peptide (BNP) Over 12 Weeks.
timeFrame: Baseline to Week 6 and Week 12
measure: Change in Hemoglobin A1c (HbA1c) Over 12 Weeks.
timeFrame: Baseline to Week 6 and Week 12
measure: Change in Weight Over 12 Weeks
timeFrame: Baseline to Week 6 and Week 12
measure: Change in Systolic Blood Pressure Over 12 Weeks
timeFrame: Baseline to Week 6 and Week 12
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: Heart Group of the Eastern Shore
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern Califiornia
state: California
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Port Charlotte
country: United States
facility: Charlotte Heart Group Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Evanston
country: United States
facility: NorthShore University HealthSystem Research Institute
state: Illinois
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Advocate Health and Hospitals
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Joplin
country: United States
facility: Freeman Health System
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: New York University
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: New Bern
country: United States
facility: Eastern Nephrology Associates
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: Saint Luke's Mid America Heart Institute
name: Mikhail Kosiborod, MD
role: STUDY_CHAIR
References:
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.
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.
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.