A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Trial to Evaluate the Effect of In-Hospital Initiation of Dapagliflozin on Clinical Outcomes in Patients With Heart Failure With Reduced Ejection Fraction Who Have Been Stabilized During Hospitalization for Acute Heart Failure DAPAgliflozin and Effect on Cardiovascular Events in ACuTe Heart Failure -Thrombolysis in Myocardial Infarction 68 (DAPA ACT HF-TIMI 68)
The primary objective of this trial is to evaluate the effect of in-hospital initiation of dapagliflozin versus placebo on the clinical outcome of cardiovascular death or worsening heart failure.
- Age ≥18 years (male or female)
- Currently hospitalized for acute heart failure (AHF) defined as meeting all the following criteria:
- Presentation with worsening symptoms of heart failure (e.g., worsening dyspnea or dyspnea at rest, progressive fatigue, rapid weight gain, worsening edema/abdominal distention/anasarca)
- Objective signs or diagnostic testing consistent with volume overload (e.g., jugular venous distension, pulmonary basilar crackles, S3 gallop, ascites, hepatomegaly, peripheral edema, radiological evidence of pulmonary congestion, noninvasive or invasive hemodynamic evidence of elevated filling pressures)
- Intensification of heart failure therapy during admission defined as at least one of the following:
- Augmentation of oral diuretic therapy [e.g., ≥2x outpatient regimen dose, the addition of a second diuretic agent, or new initiation of diuretic therapy in a previously naïve patient] ii. Initiation of intravenous diuretic therapy iii. Initiation of intravenous vasoactive agent (e.g., inotrope or vasodilator)
The majority of enrolled patients should have an established history of heart failure with reduced ejection fraction (HFrEF) (defined as present for ≥2 months and for which the patient is on treatment). Trial leadership will monitor this proportion and may cap enrollment of patients without an established history of HFrEF (i.e., patients presenting with de novo HFrEF).
- Most recent LVEF ≤40% within the past 12 months (including current hospitalization)
- Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) (≥1600 pg/mL) or B-type natriuretic peptide (BNP) (≥400 pg/mL) during current hospitalization (NT-proBNP ≥2400 pg/mL or BNP ≥600 pg/mL if patient in atrial fibrillation) (NB: for patients treated with angiotensin receptor neprilysin inhibitor (ARNI) in the 4 weeks prior to randomization, only NT-proBNP values should be used)
- Eligible patients will be randomized no earlier than 24 hours and up to seven days after presentation while still hospitalized once they have been stabilized, as defined by:
- No increase (i.e., intensification) in the dose of intravenous diuretics during the 24 hours prior to randomization
- No use of intravenous vasodilators or inotropes during the 24 hours prior to randomization
Patients with and without type 2 diabetes are eligible for participation in the trial. The trial leadership will monitor the proportion of patients with and without type 2 diabetes and may cap enrollment of one subgroup to ensure adequate representation of the other.