- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04249778
Dapagliflozin at Discharge on Hospital Heart Failure Readmission
Effect of Dapagliflozin at Discharge on Hospital Re-Admissions in Patients With Acutely Decompensated Heart Failure: A Randomized Controlled Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The prevalence of both heart failure and type 2 diabetes (T2D) or prediabetes are reaching epidemic proportions globally and in the United States. More than 40% of patients with established heart failure (HF) have diabetes.
This study will be the first trial to evaluate the safety and efficacy of dapagliflozin treatment in preventing hospital re-admissions/ER visits/urgent clinic visits, and death in patients with and without T2D after admission for heart failure. Treatment with SGLT2-i has been shown to reduce both heart failure hospitalizations and mortality in patients with established heart disease. However, the time of initiation of SGLT2-i therapy has not been evaluated in patients with HF. In addition, the impact of treatment on HF symptoms quality of life, resource utilization, and cost-effectiveness of dapagliflozin versus placebo will be evaluated. The results of this study have great potential to impact and facilitate care and to change current clinical guidelines in the management of patients with heart failure.
Patients with and without diabetes who have acute decompensated heart failure (ADHF) will be randomized to receive either dapagliflozin (10 mg once daily) or placebo at hospital discharge for 26 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Emory University Hospital
-
-
Louisiana
-
New Orleans, Louisiana, United States, 70118
- Tulane University
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19122
- Temple University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Males or females between the ages of 18 and 90 years, with ADHF, and New York Heart Association (NYHA) class II, III, or IV symptoms discharged after hospital admission with a clinical diagnosis ADHF
- Elevated natriuretic peptide tests measure levels of BNP (NT-pro-BNP) ≥300 pg/ml or B-type natriuretic peptide (BNP) ≥100 pg/ml on admission
- Interpretable echocardiogram during hospital admission (or within 12 months prior to index hospitalization)
- Blood glucose level <400 mg/dL without evidence of diabetic ketoacidosis (serum bicarbonate <18 milliequivalent (mEq)/L or positive serum or urinary ketones), in patients with T2D
Exclusion Criteria:
- Age < 18 or > 90 years
- Subjects with a history of type 1 diabetes
- Treatment with thiazolidinediones (TZDs) or SGLT2-i during the past 3 months of admission
- Recurrent episodes of severe hypoglycemia or hypoglycemic unawareness
- History of recurrent HF admissions considered to be due to non-compliance (evaluated by the research staff for participation)
- Patients with clinically significant hepatic disease (cirrhosis, jaundice, end-stage liver disease, portal hypertension) and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3 times upper limit of normal
- Patients with impaired renal function (GFR < 25 ml/min)
- Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
- Patients on ventricular assist devices (VADs)
- History of heart transplant or listed for heart transplant
- History of cardiac surgery (within 90 days prior to enrollment) or planned cardiac interventions within the following 6 months, including percutaneous coronary intervention (PCI), ablation, cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator (ICD)
- HF due to restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe stenotic valvular diseases, hypertrophic cardiomyopathy, or congenital heart disease
- History of SGLT2-i allergy
- Systolic blood pressure < 100 mmHg
- Uncontrolled hypertension, defined as a systolic blood pressure > 200 mmHg at randomization
- Female subjects who are pregnant or breast-feeding at time of enrollment into the study
- Females of childbearing potential who are not using adequate contraceptive methods
- In hospice or expected life expectancy less than 6 months
- Patients with diabetic foot infection, osteomyelitis and history of amputation of lower extremities within 6 months of admission
- Patients anticipated to undergo major surgical procedures during the following 6 months
- Patients with active hematuria, urinary tract infection (UTI), or history of frequent UTIs or genital mycotic infections
- Uncontrolled atrial fibrillation or atrial flutter with a resting heart rate >110bpm documented by ECG at randomization
- Any condition that in the opinion of the investigator would contraindicate the assessment of distance walked in 6 minutes (6MWD)
- Chronic pulmonary disease, i.e. with known forced expiratory volume in the first second (FEV1) <50% requiring home oxygen, or oral steroid therapy or current hospitalization for severe chronic obstructive pulmonary disease (COPD) thought to be a primary contributor to dyspnea, or significant chronic pulmonary disease in the Investigator's opinion, or primary pulmonary arterial hypertension
- Patients with active history of bladder cancer
- Patients with previous history of diabetic ketoacidosis, per American Diabetes Association (ADA) criteria
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dapagliflozin
Patients admitted with exacerbation of chronic heart failure by clinical and radiologic features randomized to receive 10 mg of dapagliflozin, once daily for 26 weeks.
|
Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Participants will receive 10 mg/day of dapagliflozin, beginning at hospital discharge, for 26 weeks.
Other Names:
|
Placebo Comparator: Placebo
Patients admitted with exacerbation of chronic heart failure by clinical and radiologic features randomized to receive a placebo to match 10 mg of dapagliflozin, once daily for 26 weeks.
|
Participants will receive a placebo to match 10 mg/day of dapagliflozin, beginning at hospital discharge, for 26 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Hospital Admissions, Emergency Department Visits, Urgent Clinic Visits for Heart Failure (HF) and Death After Admission With Acute Decompensated Heart Failure (ADHF)
Time Frame: Up to 26 weeks
|
The number of participants meeting criteria for a composite of hospital admissions, emergency department visits, urgent clinic visits for Heart Failure (HF) and death after admission with acute decompensated heart failure (ADHF) will be determined.
|
Up to 26 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
Time Frame: Baseline, Week 12, Week 26
|
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.
In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
|
Baseline, Week 12, Week 26
|
Chronic Heart Failure Questionnaire - Self-Administered Standardized Format (CHQ-SAS) Score
Time Frame: Baseline, Week 12, Week 26
|
Chronic Heart Failure Questionnaire - Self-Administered Standardized Format (CHQ-SAS) assesses patients' perception of their heart failure and measures the impact of heart failure symptoms.
The CHQ-SAS contains 16 standardized questions that assess dyspnea during daily activities, fatigue and emotional function.
Items are rated on a 7-point Likert scale ranging from 1 to 7. The total score is the mean of the item scores and higher scores indicate better quality of life.
|
Baseline, Week 12, Week 26
|
N-terminal (NT)-Pro Hormone BNP (NT-proBNP) Levels
Time Frame: Baseline, Week 12, Week 26
|
The heart failure, disease-specific biomarker N-terminal (NT)-pro hormone BNP (NT-proBNP) is a non-active prohormone.
Levels increase when heart failure develops or gets worse and levels goes down when heart failure is stable.
|
Baseline, Week 12, Week 26
|
6-Minute Walk Distance (6MWD)
Time Frame: Baseline, Week 12, Week 26
|
The 6-Minute Walk Distance (6MWD) test measures the distance, in meters, that a patient can quickly walk on a flat, hard surface in a period of 6 minutes
|
Baseline, Week 12, Week 26
|
Hemoglobin A1C (HbA1c) Level
Time Frame: Baseline, Week 12, Week 26
|
HbA1c will be quantified by blood test, in participants with type 2 diabetes (T2D) or prediabetes.
Higher percentages of glycated hemoglobin on red blood cells (RBCs) indicate higher blood glucose levels in the previous three months.
A normal HbA1c level is below 5.7 percent.
|
Baseline, Week 12, Week 26
|
Weight
Time Frame: Baseline,Week 12, Week 26
|
Weight is measured in kilograms
|
Baseline,Week 12, Week 26
|
Systolic Blood Pressure
Time Frame: Baseline, Week 12, Week 26
|
Systolic blood pressure is measured in millimeters of mercury (mmHg).
A normal systolic blood pressure level is less than 120 mmHg.
|
Baseline, Week 12, Week 26
|
Left Atrial Volume Index (LAVI)
Time Frame: Baseline, Week 12, Week 26
|
Left atrial volume index assesses diastolic function and is a predictor of mortality.
LAVI can identify abnormal atrial dilation and is calculated as the left atrium volume (mL) divided by body surface area (m^2).
The normal range is between 16 and 35 mL/m^2.
Increased LAVI is a predictor of mortality following acute myocardial infarction.
|
Baseline, Week 12, Week 26
|
Serum Magnesium
Time Frame: Baseline, Week 12, Week 26
|
Normal levels of serum magnesium are between 1.7 and 2.3 milligrams per deciliter (mg/dL).
|
Baseline, Week 12, Week 26
|
Number of Participants Dying From Cardiovascular Reasons
Time Frame: Up to Week 26
|
The number of participants dying due to cardiovascular reasons was documented.
|
Up to Week 26
|
Number of Participants With Non-fatal Myocardial Infarction (MI)
Time Frame: Up to Week 26
|
The number of participants with non-fatal myocardial infarction (MI) was documented.
|
Up to Week 26
|
Number of Participants With Stroke
Time Frame: Up to Week 26
|
The number of participants experiencing a stroke was documented.
|
Up to Week 26
|
Number of Participants With Acute Kidney Injury
Time Frame: Up to Week 26
|
The number of participants experiencing acute kidney injury was documented.
|
Up to Week 26
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00111588
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Heart Failure
-
Tufts Medical CenterMetro West Medical CenterCompletedCongestive Heart Failure | Diastolic Heart Failure | Systolic Heart FailureUnited States
-
Abbott Medical DevicesCompletedHeart Failure | Heart Failure, Diastolic | Heart Failure, Systolic | Heart Failure NYHA Class II | Heart Failure NYHA Class III | Heart Failure With Reduced Ejection Fraction | Heart Failure NYHA Class IV | Heart Failure With Normal Ejection Fraction | Heart Failure; With Decompensation | Heart Failure...United States, Canada
-
Manipal UniversityUnknownHeart Failure | Decompensated Heart Failure | Acute Heart Failure | Diastolic Heart Failure | Systolic Heart FailureIndia
-
VA Eastern Colorado Health Care SystemNational Institute on Aging (NIA)CompletedHeart Failure | Heart Failure, Diastolic | Heart Failure, Systolic | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection Fraction | Heart Failure; With Decompensation | Heart Failure,Congestive | Heart Failure AcuteUnited States
-
University Hospital, MontpellierCompletedHeart Failure | Diastolic Heart Failure | Systolic Heart Failure Stage CFrance
-
Wake Forest UniversityCompletedHeart Failure, Congestive | Heart Failure With Preserved Ejection Fraction
-
Wake Forest UniversityNational Institute on Aging (NIA)CompletedHeart Failure, Congestive | Diastolic Heart FailureUnited States
-
Lancaster General HospitalLouise von Hess Medical Research InstituteEnrolling by invitationDiastolic Heart FailureUnited States
-
Giresun UniversityIstanbul University - Cerrahpasa (IUC)RecruitingHeart Failure | Diastolic Heart Failure | Systolic Heart FailureTurkey
-
University of British ColumbiaCanadian Institutes of Health Research (CIHR); Duke University; St. Paul's Hospital... and other collaboratorsActive, not recruitingHeart Diseases | Heart Failure | Transplant; Failure, Heart | Heart Transplant Failure and Rejection | Heart Failure,Congestive | Transplant FailureCanada, United States
Clinical Trials on Dapagliflozin
-
Dong-A ST Co., Ltd.CompletedType2 DiabetesKorea, Republic of
-
AstraZenecaRecruitingLiver CirrhosisSpain, Denmark, Germany, United States, China, Australia, Belgium, Netherlands, Switzerland, Austria, Taiwan, Canada, Czechia
-
AstraZenecaBristol-Myers SquibbCompletedType 2 Diabetes MellitusUnited Kingdom
-
AstraZenecaNot yet recruitingChronic Kidney DiseaseUnited States, Austria, Italy, Spain, Canada, Malaysia, Taiwan, Poland, Bulgaria
-
AstraZenecaCompletedType 1 Diabetes MellitusJapan
-
AstraZenecaCompletedType 1 Diabetes MellitusJapan
-
Daewoong Pharmaceutical Co. LTD.Active, not recruitingGlucose Metabolism Disorders | Diabetes Mellitus, Type 2 | Diabetes Mellitus | Endocrine System Diseases | Metabolic DiseaseChina
-
AstraZenecaCompletedChronic Kidney DiseaseUnited States
-
Hiddo Lambers HeerspinkAstraZenecaUnknownChronic Kidney Diseases | ProteinuriaCanada, Malaysia, Netherlands
-
AstraZenecaCompletedHealthy Subjects in Fasted and Fed StateBrazil