Dapagliflozin at Discharge on Hospital Heart Failure Readmission
Condition: Heart Failure; Diabetes
MeSH terms: Heart Failure
Intervention: Dapagliflozin; Placebo
Intervention description: 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.; Participants will receive a placebo to match 10 mg/day of dapagliflozin, beginning at hospital discharge, for 26 weeks.
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: hospitalization; mortality; time of initiation of therapy; quality of life; cost-effectiveness; dapagliflozin; clinical trial; diabetes

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.
    

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