Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure -Thrombolysis in Myocardial Infarction 68 (DAPA ACT HF-TIMI 68)

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 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)

This is an international, multicenter, parallel-group, randomized, double-blind, placebo-controlled trial in patients who have been stabilized during hospitalization for acute heart failure, evaluating the effect of in-hospital initiation of dapagliflozin versus placebo on the clinical outcome of cardiovascular death or worsening heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Acute Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: Dapagliflozin

• Study Type: Interventional
• Enrollment (Actual): 2401
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • TIMI Study Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥18 years (male or female)

2. Currently hospitalized for AHF defined as meeting all the following criteria:

   1. 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)
   2. 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)
   3. Intensification of AHF therapy during admission defined as at least one of the following:

   i. Augmentation of oral diuretic therapy [e.g., ≥2x outpatient regimen dose, 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)

3. Left ventricular ejection fraction (LVEF) measured within the past 12 months (including during the current hospitalization)

4. Elevated NT-proBNP or BNP during current hospitalization:

   1. For patients with LVEF ≤40%: NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL (NT-proBNP ≥2400 pg/mL or BNP ≥600 pg/mL if patient in atrial fibrillation or atrial flutter)
   2. For patients with LVEF >40%: NT-proBNP ≥1200 pg/mL or BNP ≥300 pg/mL (NT-proBNP ≥1800 pg/mL or BNP ≥450 pg/mL if patient in atrial fibrillation or atrial flutter)

5. Eligible patients will be randomized no earlier than 24 hours and up to 14 days after presentation while still hospitalized once they have been stabilized, as defined by:

   1. No increase (i.e., intensification) in the dose of intravenous diuretics during the 12 hours prior to randomization
   2. No use of intravenous vasodilators or inotropes during the 24 hours prior to randomization

Exclusion Criteria

1. Symptomatic hypotension in the past 24 hours
2. Concurrent use of two or more intravenous inotropic agents during the index hospitalization
3. eGFR <25 ml/min/1.73 m2 as measured by the CKD-EPI equation at screening or rapidly progressive renal disease
4. Current use of an SGLT2 inhibitor
5. Prior intolerance of SGLT2 inhibitors
6. Type 1 diabetes mellitus or history of diabetic ketoacidosis
7. (Only applies to patients with T2DM who are on insulin and/or a sulfonylurea) History of recurrent major hypoglycemia (i.e., resulting in severe impairment in consciousness or behavior, or requiring emergency external assistance)
8. Implantation of a cardiac resynchronization therapy (CRT) device or valve repair or replacement within 30 days prior to randomization or intent to do so during the trial
9. ST-segment elevation myocardial infarction or coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 30 days prior to randomization or intent to undergo coronary revascularization during the trial
10. Untreated sustained ventricular arrhythmias or Mobitz type II or third-degree heart block (i.e., without an ICD or pacemaker, respectively)
11. History of heart transplantation or current transplant listing; mechanical circulatory support use (either durable or temporary) during the index hospitalization
12. History of heart failure due to restrictive or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, uncorrected primary valvular disease, complex congenital heart disease, or heart failure felt to be due to a transient process (e.g., stress [takotsubo] cardiomyopathy, tachycardia-induced cardiomyopathy) expected to resolve within 2 months.
13. History of end-stage liver disease
14. Women of child-bearing potential (unless using adequate contraception) or currently breastfeeding
15. Current participation in a clinical trial with an unlicensed drug or device
16. Study staff or their family members
17. Any condition that, in the opinion of the investigator, would make trial participation not in the best interest of the subject, or would compromise compliance with the trial protocol (e.g., active severe infection, active malignancy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin 10 mg administered orally once daily for 2 months	Drug: Dapagliflozin; Dapagliflozin
Placebo Comparator: Placebo; Matching placebo administered orally once daily for 2 months	Drug: Placebo; Matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular (CV) death or worsening heart failure	Time to first occurrence of CV death or worsening heart failure	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite CV death, rehospitalization for heart failure, urgent heart failure visit	Time to first occurrence of composite of CV death, rehospitalization for heart failure, or urgent heart failure visit	2 months
Composite CV death, rehospitalization for heart failure	Time to first occurrence of composite of CV death or rehospitalization for heart failure	2 months
Rehospitalization for heart failure, urgent heart failure visit	Time to first occurrence of rehospitalization for heart failure or urgent heart failure visit	2 months
Readmission	Readmission within 30 days of hospital discharge	2 months
CV death	Time to CV death	2 months
Death	Time to death	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic hypotension	Symptomatic hypotension leading to hospitalization or study drug discontinuation	2 months
Worsening renal function	Worsening renal function resulting in at least a doubling of serum creatinine (sCr), hospitalization, study drug discontinuation, dialysis, or renal death	2 months

Collaborators and Investigators

• Sponsor: The TIMI Study Group
• Collaborators: AstraZeneca; Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2020
• Primary Completion (Actual): June 2, 2025
• Study Completion (Actual): June 2, 2025

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; Heart Failure; Myocardial Infarction; Infarction; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: D1690C00078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes