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

NCT04363697 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: D1690C00078
• Study Type: interventional
• Target: 2,401
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Heart Failure; Heart Failure

Outcome Measures

Primary Outcomes (1)

• Cardiovascular (CV) death or worsening heart failure

  Time to first occurrence of CV death or worsening heart failure

  2 months

Secondary Outcomes (6)

• Composite CV death, rehospitalization for heart failure, urgent heart failure visit

  2 months

• Composite CV death, rehospitalization for heart failure

  2 months

• Rehospitalization for heart failure, urgent heart failure visit

  2 months

• Readmission

  2 months

• CV death

  2 months

Other Outcomes (2)

• Symptomatic hypotension

  2 months

• Worsening renal function

  2 months

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10 mg administered orally once daily for 2 months

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Matching placebo administered orally once daily for 2 months

Drug: Placebo

Interventions

Dapagliflozin DRUG

Dapagliflozin

Dapagliflozin

Placebo DRUG

Matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years (male or female)
• Currently hospitalized for 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 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)
• Left ventricular ejection fraction (LVEF) measured within the past 12 months (including during the current hospitalization)
• Elevated NT-proBNP or BNP during current hospitalization:
• 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)
• 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)
• 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:
• No increase (i.e., intensification) in the dose of intravenous diuretics during the 12 hours prior to randomization
• No use of intravenous vasodilators or inotropes during the 24 hours prior to randomization

You may not qualify if:

• Symptomatic hypotension in the past 24 hours
• Concurrent use of two or more intravenous inotropic agents during the index hospitalization
• eGFR \<25 ml/min/1.73 m2 as measured by the CKD-EPI equation at screening or rapidly progressive renal disease
• Current use of an SGLT2 inhibitor
• Prior intolerance of SGLT2 inhibitors
• Type 1 diabetes mellitus or history of diabetic ketoacidosis
• (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)
• 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
• 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
• Untreated sustained ventricular arrhythmias or Mobitz type II or third-degree heart block (i.e., without an ICD or pacemaker, respectively)
• History of heart transplantation or current transplant listing; mechanical circulatory support use (either durable or temporary) during the index hospitalization
• 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.
• History of end-stage liver disease
• Women of child-bearing potential (unless using adequate contraception) or currently breastfeeding
• Current participation in a clinical trial with an unlicensed drug or device

Sponsors & Collaborators

• The TIMI Study Group: lead
• AstraZeneca: collaborator
• Worldwide Clinical Trials: collaborator

Study Sites (1)

TIMI Study Group

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Berg DD, Patel SM, Haller PM, Cange AL, Palazzolo MG, Bellavia A, Kuder JF, Desai AS, Inzucchi SE, McMurray JJV, O'Meara E, Verma S, Belohlavek J, Drozdz J, Merkely B, Ogunniyi MO, Drasnar T, Izzo JL, Sarman B, McGinty JE, Ramanathan K, Mulkay AJ, Przybylski A, Ruff CT, O'Donoghue ML, Murphy SA, Sabatine MS, Wiviott SD; DAPA ACT HF-TIMI 68 Trial Committees and Investigators. Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Patients Hospitalized for Heart Failure. Circulation. 2025 Nov 18;152(20):1411-1422. doi: 10.1161/CIRCULATIONAHA.125.076575. Epub 2025 Aug 29.

  PMID: 40884036 DERIVED

• Berg DD, Patel SM, Haller PM, Belohlavek J, Desai AS, Drozdz J, Inzucchi SE, McMurray JJV, Merkely B, O'Meara E, Verma S, Cange AL, Murphy SA, Sabatine MS, Wiviott SD. Rationale and Design of the Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure (DAPA ACT HF)-TIMI 68 Trial. JACC Heart Fail. 2025 May;13(5):829-839. doi: 10.1016/j.jchf.2025.03.014.

  PMID: 40335233 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: September 24, 2020
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)