Clinical trial NCT04249778: Dapagliflozin at Discharge on Hospital Heart Failure Readmission
Official title: Effect of Dapagliflozin at Discharge on Hospital Re-Admissions in Patients With Acutely Decompensated Heart Failure: A Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Diabetes
Keywords: hospitalization
mortality
time of initiation of therapy
quality of life
cost-effectiveness
dapagliflozin
clinical trial
diabetes
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2020-01-31
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Hospital Admissions, Emergency Department Visits, Urgent Clinic Visits, and Death
timeFrame: Up to 26 weeks
Secondary outcomes:
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
timeFrame: Baseline, Week 12, Week 26
measure: Chronic Heart Failure Questionnaire - Self-Administered Standardized Format (CHQ-SAS) Score
timeFrame: Baseline, Week 12, Week 26
measure: N-terminal (NT)-Pro Hormone BNP (NT-proBNP) Levels
timeFrame: Baseline, Week 12, Week 26
measure: 6-Minute Walk Distance (6MWD)
timeFrame: Baseline, Week 12, Week 26
measure: Hemoglobin A1C (HbA1c) Level
timeFrame: Baseline, Week 12, Week 26
measure: Weight
timeFrame: Baseline,Week 12, Week 26
measure: Systolic Blood Pressure
timeFrame: Baseline, Week 12, Week 26
measure: Left Atrial Diameter
timeFrame: Baseline, Week 12, Week 26
measure: Serum Magnesium
timeFrame: Baseline, Week 12, Week 26
measure: Number of Participants Dying From Cardiovascular Reasons
timeFrame: Up to Week 26
measure: Number of Participants With Non-fatal Myocardial Infarction (MI)
timeFrame: Up to Week 26
measure: Number of Participants With Stroke
timeFrame: Up to Week 26
measure: Number of Participants With Acute Kidney Injury
timeFrame: Up to Week 26
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
Study officials:
affiliation: Emory University
name: Guillermo Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References: