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Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes

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Abstract

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure (HF). This syndrome is associated with an elevated morbi-mortality, and effective therapies are urgently needed. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the first pharmacological class that has demonstrated to reduce hospitalization and cardiovascular mortality in large clinical trials in HFpEF. Furthermore, the dual SGLT 1/2 inhibitor sotagliflozin has shown a reduction in cardiovascular outcomes in diabetic HF patients, regardless of ejection fraction Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) Trial, and prevents the development of HF in patients with diabetes and chronic kidney disease Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial. The major objective of the Sotagliflozin in Heart Failure With Preserved Ejection Fraction Patients (SOTA-P-CARDIA) trial (NCT05562063) is to investigate whether the observed cardiorenal benefits of sotagliflozin in HF patients with diabetes can be extended to a non-diabetic population. The SOTA-P-CARDIA is a prospective, randomized, double-blinded, placebo-controlled study that will randomize non-diabetic patients with the universal definition of HFpEF (ejection fraction > 50% assessed the day of randomization). Qualifying patients will be randomized, in blocks of 4, to receive either sotagliflozin or placebo for a period of 6 months. The primary outcome is changes in left ventricular mass by cardiac magnetic resonance from randomization to end of the study between the groups. Secondary end points include changes in peak VO2; myocardial mechanics, interstitial myocardial fibrosis, and volume of epicardial adipose tissue; distance in the 6-min walk test; and quality of life. Finally, the authors expect that this trial will help to clarify the potential benefits of the use of sotagliflozin in non-diabetic HFpEF patients.

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Funding

This study has been funded by an Investigator-Initiated Grant to Dr. Badimon by Lexicon Pharmaceuticals, Inc. Dr Requena-Ibañez was sup- ported by a fellowship from La Caixa Foundation (ID 100010434). The fellowship code is LCF/BQ/EU21/11890141.

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Authors and Affiliations

  1. Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl, New York, NY, 10029-0310, USA

    Maeve Soto Pérez, Jorge Rodríguez-Capitán, Juan Antonio Requena-Ibáñez, Carlos G. Santos-Gallego, M. Urooj Zafar, Ginés Escolar & Juan José Badimon

  2. Cardiology Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

    Maeve Soto Pérez

  3. Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Cardiology Department (Hospital, Universitario Virgen de La Victoria), IBIMA-Plataforma BIONAND, Universidad de Málaga, Málaga, Spain

    Jorge Rodríguez-Capitán

  4. Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, USA

    Juan Antonio Requena-Ibáñez, Carlos G. Santos-Gallego, M. Urooj Zafar, Donna Mancini, Sumeet Mitter, Johanna P. Contreras, Icilma Fergus, Farah Atallah-Lajam, Vivian Abascal, Anu Lala, Pedro Moreno, Noah Moss, Stamatios Lerakis, Javier Sanz, Valentin Fuster & Juan José Badimon

  5. Department of Hematopathology, Hospital Clinic, Barcelona, Spain

    Ginés Escolar

  6. Endocrine, Diabetes and Bone Diseases. Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, USA

    David Lam

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  1. Maeve Soto Pérez
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All authors have read, approved, and contributed equally to the final version of the manuscript.

Corresponding authors

Correspondence to Maeve Soto Pérez, Jorge Rodríguez-Capitán or Juan José Badimon.

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All procedures performed in studies involving human participants are 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. The protocol was approved by the Mount Sinai Institutional Review Board (GCO 22–0574) and received IND 165123 by the FDA.

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This study has been funded by an Investigator-Initiated Grant to Dr. Badimon by Lexicon Pharmaceuticals, Inc.

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Pérez, M.S., Rodríguez-Capitán, J., Requena-Ibáñez, J.A. et al. Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07469-6

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