Dapagliflozin at Discharge on Hospital Heart Failure Readmission

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04249778
• Other study ID #: IRB00111588
• Status: Completed
• Phase: Phase 4
• Start date: July 29, 2020
• Est. completion date: March 3, 2022

Study information

• Verified date: May 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and efficacy of dapagliflozin treatment in preventing hospital re-admissions, emergency room (ER) visits, urgent clinic visits, and death in patients with and without type 2 diabetes (T2D) after hospital admission for heart failure.

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.

Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor (SGLT2-i) indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D mellitus. 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. 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 hospital admission for heart failure. 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 take either dapagliflozin or placebo daily for 26 weeks, beginning at the time of discharge from from the hospital.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: March 3, 2022
• Est. primary completion date: March 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

1. 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

2. 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

3. Interpretable echocardiogram during hospital admission (or within 12 months prior to index hospitalization)

4. 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:

1. Age < 18 or > 90 years

2. Subjects with a history of type 1 diabetes

3. Treatment with thiazolidinediones (TZDs) or SGLT2-i during the past 3 months of admission

4. Recurrent episodes of severe hypoglycemia or hypoglycemic unawareness

5. History of recurrent HF admissions considered to be due to non-compliance (evaluated by the research staff for participation)

6. 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

7. Patients with impaired renal function (GFR < 25 ml/min)

8. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study

9. Patients on ventricular assist devices (VADs)

10. History of heart transplant or listed for heart transplant

11. 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)

12. HF due to restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe stenotic valvular diseases, hypertrophic cardiomyopathy, or congenital heart disease

13. History of SGLT2-i allergy

14. Systolic blood pressure < 100 mmHg

15. Uncontrolled hypertension, defined as a systolic blood pressure > 200 mmHg at randomization

16. Female subjects who are pregnant or breast-feeding at time of enrollment into the study

17. Females of childbearing potential who are not using adequate contraceptive methods

18. In hospice or expected life expectancy less than 6 months

19. Patients with diabetic foot infection, osteomyelitis and history of amputation of lower extremities within 6 months of admission

20. Patients anticipated to undergo major surgical procedures during the following 6 months

21. Patients with active hematuria, urinary tract infection (UTI), or history of frequent UTIs or genital mycotic infections

22. Uncontrolled atrial fibrillation or atrial flutter with a resting heart rate >110bpm documented by ECG at randomization

23. Any condition that in the opinion of the investigator would contraindicate the assessment of distance walked in 6 minutes (6MWD)

24. 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

25. Patients with active history of bladder cancer

26. Patients with previous history of diabetic ketoacidosis, per American Diabetes Association (ADA) criteria

Related Conditions & MeSH terms

• Diabetes
• Heart Failure

Intervention

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, beginning at hospital discharge, for 26 weeks.
• Placebo
Participants will receive a placebo to match 10 mg/day of dapagliflozin, beginning at hospital discharge, for 26 weeks.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Tulane University	New Orleans	Louisiana
United States	Temple University	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Hospital Admissions, Emergency Department Visits, Urgent Clinic Visits, and Death	The number of participants meeting criteria for a composite of hospital admissions, emergency department visits, urgent clinic visits for heart failure and death after admission with acute decompensated heart failure (ADHF) was determined.	Up to 26 weeks
Secondary	Kansas City Cardiomyopathy Questionnaire (KCCQ) Score	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
Secondary	Chronic Heart Failure Questionnaire - Self-Administered Standardized Format (CHQ-SAS) Score	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
Secondary	N-terminal (NT)-Pro Hormone BNP (NT-proBNP) Levels	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 reduce when heart failure is stable.	Baseline, Week 12, Week 26
Secondary	6-Minute Walk Distance (6MWD)	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
Secondary	Hemoglobin A1C (HbA1c) Level	HbA1c was quantified by blood test, in participants with type 2 diabetes (T2D). 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
Secondary	Weight	Weight is measured in kilograms.	Baseline,Week 12, Week 26
Secondary	Systolic Blood Pressure	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
Secondary	Left Atrial Diameter	The normal range for left atrial diameter is 2.0 to 4.0 centimeters (cm). The left atrium increases in size with heart conditions.	Baseline, Week 12, Week 26
Secondary	Serum Magnesium	Normal levels of serum magnesium are between 1.7 and 2.3 milligrams per deciliter (mg/dL).	Baseline, Week 12, Week 26
Secondary	Number of Participants Dying From Cardiovascular Reasons	The number of participants dying due to cardiovascular reasons was documented.	Up to Week 26
Secondary	Number of Participants With Non-fatal Myocardial Infarction (MI)	The number of participants with non-fatal myocardial infarction (MI) was documented.	Up to Week 26
Secondary	Number of Participants With Stroke	The number of participants experiencing a stroke was documented.	Up to Week 26
Secondary	Number of Participants With Acute Kidney Injury	The number of participants experiencing acute kidney injury was documented.	Up to Week 26