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Rationale and Design of the EMPA-TROPISM Trial (ATRU-4): Are the “Cardiac Benefits” of Empagliflozin Independent of its Hypoglycemic Activity?

  • Carlos G. Santos-Gallego
  • Alvaro Garcia-Ropero
  • Donna Mancini
  • Sean P. Pinney
  • Johanna P. Contreras
  • Icilma Fergus
  • Vivian Abascal
  • Pedro Moreno
  • Farah Atallah-Lajam
  • Ronald Tamler
  • Anu Lala
  • Javier Sanz
  • Valentin Fuster
  • Juan Jose BadimonEmail author
ORIGINAL ARTICLE
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Abstract

The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF < 50%, and New York Heart Association functional class II to IV symptoms will be randomized to empagliflozin 10 mg for 6 months or placebo. All patients will undergo cardiac magnetic resonance (CMR), cardiopulmonary exercise test (CPET), 6-min walk test, and quality of life questionnaires. The primary outcome is the change in left ventricular end-diastolic volume measured by CMR. Secondary end-points include change in peak VO2 (CPET); change in LV mass, in LVEF, in myocardial mechanics (strains), in left atrium volumes, in RV function and volumes, in interstitial myocardial fibrosis, and in epicardial adipose tissue (CMR); change in the distance in the 6-min walk test; and changes in quality of life (Kansas Cardiomyopathy questionnaire [KCCQ-12] and the 36-Item Short Form Survey [SF-36]). Safety issues (e.g., hypoglycemia, urinary infections, ketoacidosis,…) will also be monitored. In summary, EMPA-TROPISM clinical trial will determine whether the SGLT2 inhibitor empagliflozin improves cardiac function and heart failure parameters in non-diabetic HF patients (EMPA-TROPISM [ATRU-4]: Are the “cardiac benefits” of Empagliflozin independent of its hypoglycemic activity; NCT 03485222).

Keywords

Heart failure Empagliflozin SGLT2-inhibitors Diabetes mellitus Cardiac magnetic resonance Cardiopulmonary exercise test Cardiac remodeling 

Notes

Funding

This study has been funded by an Investigator-Initiated Grant (2456–0179) to Dr. Badimon by Boehringer-Ingelheim.

Compliance with Ethical Standards

Conflicts of Interest

Dr. Juan J. Badimon has received an Investigator-Initiated Award from Boehringer-Ingelheim to fund this trial. Dr. Carlos G. Santos-Gallego declares that he has no conflict of interest. Dr. Alvaro Garcia-Ropero declares that he has no conflict of interest. Dr. Donna Mancini has nothing to declare. Dr. Sean P. Pinney declares that he has no conflict of interest. Dr. Johanna P. Contreras declares that she has no conflict of interest. Dr. Icilma Fergus declares that she has no conflict of interest. Dr. Vivian Abascal declares that she has no conflict of interest. Dr. Pedro Moreno declares that he has no conflict of interest. Dr. Farah Atallah-Lajam declares that he has no conflict of interest. Dr. Ronald Tamler declares that he has no conflict of interest. Dr. Anu Lala declares that he has no conflict of interest. Dr. Javier Sanz declares that he has no conflict of interest. Dr. Valentin Fuster declares that he has no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent will be obtained from all individual participants included in the study.

Disclosures

This study has been funded by an Investigator-Initiated Grant (1245–0179) provided to Dr. Badimon by Boehringer-Ingelheim.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Carlos G. Santos-Gallego
    • 1
    • 2
  • Alvaro Garcia-Ropero
    • 1
    • 2
  • Donna Mancini
    • 2
  • Sean P. Pinney
    • 2
  • Johanna P. Contreras
    • 2
  • Icilma Fergus
    • 2
  • Vivian Abascal
    • 2
  • Pedro Moreno
    • 2
  • Farah Atallah-Lajam
    • 2
  • Ronald Tamler
    • 3
  • Anu Lala
    • 2
  • Javier Sanz
    • 2
  • Valentin Fuster
    • 2
  • Juan Jose Badimon
    • 1
    Email author
  1. 1.Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai HospitalNew York CityUSA
  2. 2.Cardiovascular Institute, Icahn School of Medicine at Mount Sinai HospitalNew York CityUSA
  3. 3.Mount Sinai Clinical Diabetes InstituteNew York CityUSA

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