Dapagliflozin at Discharge on Hospital Heart Failure Readmission

Sponsor

Emory University (Other)

Overall Status

Completed

CT.gov ID

NCT04249778

Collaborator

(none)

Enrollment

Locations

Arms

19.1

Actual Duration (Months)

22.3

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be the first trial to evaluate the safety and efficacy of dapagliflozin treatment in preventing readmissions/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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Diabetes	Drug: Dapagliflozin Drug: Placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effect of Dapagliflozin at Discharge on Hospital Re-Admissions in Patients With Acutely Decompensated Heart Failure: A Randomized Controlled Study

Actual Study Start Date :

Jul 29, 2020

Actual Primary Completion Date :

Mar 3, 2022

Actual Study Completion Date :

Mar 3, 2022

Arms and Interventions

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	Drug: Dapagliflozin 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. Other Names: FARXIGA
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	Drug: Placebo Participants will receive a placebo to match 10 mg/day of dapagliflozin.

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

Drug: Dapagliflozin

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.

Other Names:

FARXIGA

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

Drug: Placebo

Participants will receive a placebo to match 10 mg/day of dapagliflozin.

Outcome Measures

Primary Outcome Measures

Composite number of hospital admissions, emergency department visits, urgent clinic visits for Heart Failure (HF) and death after admission with acute decompensated heart failure (ADHF) [26 weeks]
Composite number 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 calculated

Secondary Outcome Measures

Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score [Baseline, 12, and 26 weeks]
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.
Change in the Chronic Heart Failure Questionnaire (CHQ-SAS) score [Baseline, 12, and 26 weeks]
The Chronic Heart Failure Questionnaire (CHQ-SAS) assesses patients' perception of their HF and measures the impact of HF symptoms. The CHQ-SAS contains16 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.
Change in NT-proBNP levels [Baseline, 12, and 26 weeks]
Lower HF disease-specific biomarker N-terminal (NT)-pro hormone BNP (NT-proBNP) is a non-active prohormone. Levels goes up when heart failure develops or gets worse, and levels goes down when heart failure is stable. NT-proBNP levels will be quantified by blood test
Change in 6-minute walk distance (6MWD) [Baseline, 12, and 26 weeks]
This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes
Change in HbA1c [Baseline, 12, and 26 weeks]
Change in HbA1c will be quantified by blood test, in participants with T2D
Change in weight [Baseline,12, and 26 weeks]
Weight is measured in pounds
Change in systolic blood pressure [Baseline, 12, and 26 weeks]
Systolic blood pressure is measured in millimeters of mercury (mmHg).
Change in left atrial volume index and measures of left ventricular systolic and diastolic function [Baseline, 12, and 26 weeks]
Change in left atrial volume index and measures of left ventricular systolic and diastolic function will be assessed by echocardiogram. This will be done in patients who may undergo repeated echocardiogram during follow up.
Change in serum magnesium [Baseline, 12, and 26 weeks]
Serum magnesium will be quantified by blood test
Number of cardiovascular death cases [26 weeks]
Number of cardiovascular death cases will be documented
Number of non-fatal myocardial infarction (MI) cases [26 weeks]
Number of non-fatal myocardial infarction (MI) cases will be documented
Number of stroke cases [26 weeks]
Number of stroke cases will be documented
Number of acute kidney injury cases [26 weeks]
Number of acute kidney injury cases will be documented

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 NT-pro-BNP ≥300 pg/ml or 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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital	Atlanta	Georgia	United States	30322
2	Tulane University	New Orleans	Louisiana	United States	70118
3	Temple University	Philadelphia	Pennsylvania	United States	19122