Table 2:
Recent and Ongoing Clinical Trials Evaluating In-hospital Initiation of SGLT2i Therapy for Patients Admitted for Acute Heart Failure
| Trial | Design | Follow-up | Outcomes |
|---|---|---|---|
| Completed | |||
| SOLOIST-WHF (NCT 03521934) | Randomized, double-blind multicenter trial. 1222 patients hospitalized with AHF were randomized 1:1 to sotagliflozin 200–400 mg or placebo during hospitalization or within 3 days of discharge. Included only patients with T2DM and eGFR ≥ 30 ml/min/1.73m2. Trial ended early because of loss of funding from sponsor. | Outpatient | Sotagliflozin reduced the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (primary endpoint). Diarrhea and severe hypoglycemia were more common in the sotagliflozin group. |
| EMPA-RESPONSE-AHF (NCT 03200860) | Randomized, double blind pilot study. 80 patients hospitalized with AHF were randomized in the first 24 hours of hospitalization 1:1 to either empagliflozin 10 mg daily or placebo for 30 days. Included patients with and without T2DM. All patients had eGFR ≥ 30 ml/min/1.73m2. Loop diuretic use was non-standardized. | In-hospital | There were no differences in the primary endpoints assessed on day 4 of hospitalization: change in VAS dyspnea score, weight change per 40 mg IV furosemide, length of stay, and change in NT-proBNP. Rates of adverse events were similar between groups. |
| Ongoing | |||
| DICTATE-AHF (NCT 04298229) | Randomized, open-label, blinded adjudication. 240 patients hospitalized with AHF randomized in the first 24 hours of hospitalization 1:1 to dapagliflozin or usual care until day 5 or hospital discharge. All patients have T2DM and receive diuretic and insulin therapies per protocol. All patients with eGFR ≥ 30. | In-hospital | Primary endpoint is weight change per 40 mg furosemide equivalent on day 5. Key safety endpoints include adverse diabetes-related events while hospitalized: incidence of hyper/ hypoglycemia, ketoacidosis, and hypovolemic hypotension. |
| Ertugliflozin in AHF (NCT 04438213) | Randomized, double-blind mechanistic study. 90 patients hospitalized with AHF randomized 1:1:1 to ertugliflozin, metolazone, or placebo. All patients receive non-standardized loop diuretic therapy. All patients have eGFR ≥ 30 ml/min/1.73m2 with or without T2DM. | In-hospital and outpatient | Primary endpoint is change in urine sodium and total body water at days 1, 7, and 42. |
| EMPULSE (NCT 04157751) | Randomized, double-blind study. 530 patients hospitalized for AHF on day 2–5 randomized 1:1 to empagliflozin 10 mg or placebo. Patients must be stabilized with SBP >100 mmHg, no IV vasodilators or increase in IV loop diuretics in 6 h and no IV inotropes in 24 h. Includes both HFpEF and HFrEF patients. eGFR ≥ 20 ml/min/1.73m2. | Outpatient | Primary endpoint is composite of death, number of heart failure events, time to first heart failure event, and ≥ 5 point KCCQ-TSS score change at 90 days using a “win-ratio” approach. |
| DAPA ACT HF-TIMI 68 (NCT 04363697) | Randomized, double-blind study. 2400 patients hospitalized with AHF randomized 1:1 to dapagliflozin 10 mg vs placebo on hospital day 2–7. Patients must be stabilized with no increase in IV loop diuretics in and no IV vasodilator or inotropes in 24 h. eGFR ≥ 30 ml/min/1.73m2. | Outpatient | Primary endpoint through 60 days is time to first cardiovascular death or worsening heart failure. |
Abbreviations: AHF, acute heart failure; T2DM, type 2 diabetes mellitus; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IV, intravenous; NT-proBNP, N-terminal-pro hormone brain natriuretic peptide; KCCQ-TSS, The Kansas City Cardiomyopathy Questionnaire Total Symptom Score.