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Phase 4 Completed N=84 Randomized Double-blind Treatment

Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? (ATRU-4).

Source: ClinicalTrials.gov NCT03485222 ↗
Enrolled (actual)
84
Serious AEs
3.8%
Results posted
Mar 2021
Primary outcomePrimary: Change in Left Ventricle-end Systolic Volume (ESV) — -26.6; -0.5 ml
◆ Published Evidence
Highly cited
518citations · ~104 / year
Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.
Journal of the American College of Cardiology · 2021 · High-confidence link

Summary

Purpose: The overall hypothesis of the study is that the benefits attained in the EMPA-OUTCOME were, at least in part, mediated by a glucose-independent mechanism. Thus, to demonstrate the existence of the postulated non-glucose dependent effects, the researchers will investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in heart failure patients with reduced ejection fraction without diabetes.

Linked Publications (5)

  • Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.
    Journal of the American College of Cardiology · 2021 · 518 citations · High-confidence link
  • Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF: From the EMPA-TROPISM Study.
    JACC. Heart failure · 2021 · 258 citations · Likely link
  • Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.
    The Cochrane database of systematic reviews · 2021 · 58 citations · Open access · Likely link
  • Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure.
    Nature cardiovascular research · 2023 · 51 citations · Open access · Likely link
  • Anaemia predicts iron homoeostasis dysregulation and modulates the response to empagliflozin in heart failure with reduced ejection fraction: the EMPATROPISM-FE trial.
    European heart journal · 2025 · 20 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Left Ventricle-end Systolic Volume (ESV)
-26.6; -0.5
PRIMARY
Change in LV-end Diastolic Volume (EDV)
-25.1; -1.5
SECONDARY
Change in LV-Ejection Fraction Index
6.0; -0.1
SECONDARY
Change in VO2 Consumption
1.1; -0.5
SECONDARY
Change in 6 Min Walk Test
81; -35
SECONDARY
Change in Kansas Cardiomyopathy Questionnaire (KCCQ-12)
21; 1.9

Eligibility Criteria

Inclusion Criteria

  • Patients should meet the following inclusion criteria:
  • Ambulatory patients age 18-85 years
  • Diagnosis of Heart failure (NYHA II to III)
  • LVEF<50% on echocardiography or CMRI in the previous 6 months
  • Have stable symptoms and therapy for HF within the last 3 months.

Exclusion Criteria

  • Pregnant or lactating women.
  • Any history of diabetes by medical history or by any of the established criteria by the American Diabetes Association. It also includes patients with history of diabetes in remission.
  • ACS or cardiac surgery within the last 3 months.
  • Cancer or any other life-threatening condition.
  • Pancreatitis.
  • Glomerular Filtration Rate < 45 ml/Kg/min.
  • Use of continuous parental inotropic agents.
  • Systolic BP < 90 mm Hg.
  • Psychiatric disease incompatible with being in study.
  • Any contraindication to MRI procedures.
  • Any other medical or physical condition considered to be inappropriate by a study physician.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03485222) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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