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NCT03485222: EMPA-TROPISM

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

Completed Phase 4 Results posted Last updated 25 March 2021
What this trial tests

Phase 4 trial testing Empagliflozin in Cardiovascular Diseases in 84 participants. Completed in 13 February 2020.

Timeline
21 May 2018
Primary endpoint
13 February 2020
13 February 2020

Quick facts

Lead sponsorIcahn School of Medicine at Mount Sinai
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment84
Start date21 May 2018
Primary completion13 February 2020
Estimated completion13 February 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Icahn School of Medicine at Mount Sinai

Who can join

18 and older, any sex, with Cardiovascular Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Left Ventricle-end Systolic Volume (ESV) Primary · Baseline and 6 months

End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction of the left ventricle (LV). Change from baseline to study end at 6 months.

GroupValue95% CI
Empagliflozin-26.6± 20.5
Placebos-0.5± 21.9
Change in LV-end Diastolic Volume (EDV) Primary · Baseline and 6 months

End-diastolic volume (EDV) is the volume of blood in the left ventricle at end load or filling in (diastole) or the amount of blood in the ventricles just before systole. Change from baseline to study end at 6 months.

GroupValue95% CI
Empagliflozin-25.1± 26
Placebos-1.5± 25.4
Change in LV-Ejection Fraction Index Secondary · Baseline and 6 months

The volumetric fraction of blood ejected from the left ventricle of the heart with each heartbeat. Change from baseline to study end at 6 months.

GroupValue95% CI
Empagliflozin6.0± 4.2
Placebos-0.1± 3.9
Change in VO2 Consumption Secondary · Baseline and 6 months

Oxygen consumption - the amount of oxygen consumed by the tissues of the body, usually measured as the oxygen uptake in the lung, also called the V02max measure. Change from baseline to study end at 6 months.

GroupValue95% CI
Empagliflozin1.1± 2.6
Placebos-0.5± 1.9
Change in 6 Min Walk Test Secondary · Baseline and 6 months

The distance covered over a time of 6 minutes. Change from baseline to study end at 6 months.

GroupValue95% CI
Empagliflozin81± 64
Placebos-35± 68
Change in Kansas Cardiomyopathy Questionnaire (KCCQ-12) Secondary · Baseline and 6 months

The KCCQ-12 is an instrument most widely used to evaluate QoL in Heart Failure (HF) patients. It is a questionnaire containing 12 questions with full scores ranging from 12 (poor quality of life) to 70 (good quality of life). Higher score indicates better quality of life. Change from baseline to study end at 6 months.

GroupValue95% CI
Empagliflozin21± 18
Placebos1.9± 15

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Empagliflozin
Serious: 1/40 (3%)
Deaths: 0/40
Placebos
Serious: 2/40 (5%)
Deaths: 1/40

Serious adverse events (6 terms)

ReactionSystemEmpagliflozinPlacebos
Ventricular FibrillationCardiac disorders
Pleural EffusionRespiratory, thoracic and mediastinal disorders
New ICD ImplantCardiac disorders
Malignant Ventricular TachycardiaCardiac disorders
Worsening Heart FailureCardiac disorders
New Cardiomems ImplantCardiac disorders
Other adverse events (3 terms — click to expand)

ReactionSystemEmpagliflozinPlacebos
Hepatic InjuryHepatobiliary disorders
MigraineNervous system disorders
Motor Vehicle AccidentSocial circumstances

Most-reported serious reactions: Ventricular Fibrillation, Pleural Effusion, New ICD Implant, Malignant Ventricular Tachycardia, Worsening Heart Failure, New Cardiomems Implant.

Data from ClinicalTrials.gov NCT03485222 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mitochondrial dysfunction in pathophysiology of heart failure.
    Zhou B, Tian R. · · 2018 · cited 678× · PMID 30124471 · DOI 10.1172/jci120849
  2. Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.
    Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, Garcia-Ropero A, et al · · 2021 · cited 378× · PMID 33197559 · DOI 10.1016/j.jacc.2020.11.008
  3. Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF: From the EMPA-TROPISM Study.
    Requena-Ibáñez JA, Santos-Gallego CG, Rodriguez-Cordero A, Vargas-Delgado AP, et al · · 2021 · cited 203× · PMID 34325888 · DOI 10.1016/j.jchf.2021.04.014
  4. Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes.
    Iborra-Egea O, Santiago-Vacas E, Yurista SR, Lupón J, et al · · 2019 · cited 71× · PMID 31998851 · DOI 10.1016/j.jacbts.2019.07.010
  5. The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions.
    Lan NSR, Fegan PG, Yeap BB, Dwivedi G. · · 2019 · cited 54× · PMID 31400090 · DOI 10.1002/ehf2.12505
  6. Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure.
    Angermann CE, Santos-Gallego CG, Requena-Ibanez JA, Sehner S, et al · · 2023 · cited 44× · PMID 39196095 · DOI 10.1038/s44161-023-00352-5
  7. Effect of sodium-glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis.
    Yu YW, Zhao XM, Wang YH, Zhou Q, et al · · 2021 · cited 32× · PMID 33494751 · DOI 10.1186/s12933-020-01209-y
  8. Inhibition of Sodium Glucose Cotransporters Improves Cardiac Performance.
    García-Ropero Á, Vargas-Delgado AP, Santos-Gallego CG, Badimon JJ. · · 2019 · cited 32× · PMID 31277431 · DOI 10.3390/ijms20133289

Verify or expand the search:

Other trials of Empagliflozin

Trials testing the same drug.

Other recruiting trials for Cardiovascular Diseases

Currently open trials in the same condition.

Other Icahn School of Medicine at Mount Sinai trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03485222.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing