Antithrombotic Activities of Sotagliflozin vs. Empagliflozin (SOTATHROMBUS)

SOTA-THROMBOSIS: Antithrombotic Activities of Sotagliflozin vs. Empagliflozin

The availability of Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) has dramatically altered the management of heart failure (HF) patients, independently of their ejection fraction and glycemic status. A meta-analysis of 57 studies comparing SGLT2-I monotherapy vs. placebo or active comparator showed reductions in major cardiovascular events, but no impact on atherothrombotic events. In fact, a non-significant increase in the risk for non-fatal stroke was observed. Similar trend observed in multiple trials indicate a SGLT2-i class effect. Sotagliflozin is the first dual SGLT1/2 receptor inhibitor, that was shown to significantly reduce atherothrombotic events compared with placebo in diabetic HF patients, suggesting that dual SGLT1/2 inhibitor may have additional properties vs. SGLT2-i. The hypothesis of this study is that dual SGLT1/2 inhibition by sotagliflozin improves thrombogenic profile (i.e. reduces thrombus formation), which could make it a safer and more effective treatment option for cardiovascular (CV) patients than SGLT2-i. To test the hypothesis, the researchers will compare the antithrombotic activity of sotagliflozin vs. empagliflozin in healthy volunteers using a randomized, cross-over study design, where each participant will receive both study treatments (sotagliflozin and empagliflozin) separated by a washout period. Treatment effects will be assessed by measuring ex vivo thrombus formation using the Badimon Perfusion chamber, platelet aggregation using Multiplate Analyzer, and Thromboelastometry using RoTEM Gamma. Study assessments will be performed before initiating (baseline/pre-treatment) and after completion of each treatment.

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: Sotagliflozin; Drug: Empagliflozin

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Subjects are eligible if they meet all of the following criteria:

• Male or female volunteers older than 18 years old.
• Disease-free as assessed by medical history and physical examination.
• Ability to provide signed informed consent.

Exclusion criteria:

Subjects will be excluded if they meet any of the following criteria:

• Pregnant or lactating women
• History of clinically relevant cardiovascular, pulmonary, hepatic, gastrointestinal, renal, metabolic, hematologic, neurologic, respiratory or psychiatric disease, bleeding, acute infectious disease or signs of acute illness.
• Use of medication within one month prior to study drug administration or within six times the elimination half-life (whichever is longer), except for oral contraceptives or occasional use of acetaminophen or an antihistamine.
• History of drug abuse or alcohol consumption >20 g/day [125 ml (30ml=1oz) glass of 10% wine = 12.5 g, 40 mL aperitif of 40% = 17 g, 250 mL glass of 6% beer = 15g]
• Loss of >400 mL blood or blood donation within 3 months.
• Conditions associated with hemorrhagic risk, e.g., frequent epistaxis, gastrointestinal ulcer, hemorrhagic vascular lesions, recent surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sotagliflozin then Empagliflozin; Subjects randomized to 'Arm A' will receive 1-month of 'Sotagliflozin' treatment first and then 1-month of 'Empagliflozin' treatment second, separated by a 1-month of washout period.	Drug: Sotagliflozin; Sotagliflozin 400 mg, P.O. once daily for 1 month.; Drug: Empagliflozin; Empagliflozin 10 mg, P.O. once daily for 1 month.
Other: Empagliflozin then Sotagliflozin; Subjects randomized to 'Arm B' will receive1-month of 'Empagliflozin' treatment first and then1-month of 'Sotagliflozin' treatment second, separated by a 1-month of washout peri od	Drug: Sotagliflozin; Sotagliflozin 400 mg, P.O. once daily for 1 month.; Drug: Empagliflozin; Empagliflozin 10 mg, P.O. once daily for 1 month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombus size	Changes in blood thrombogenicity (thrombus size) from baseline to post-treatment	Baseline and end of each treatment period (1 month and 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet aggregation	A platelet aggregation is a blood test that looks at the reactivity of platelets.	Baseline and end of each treatment period (1 month and 3 months)
Clot formation size	The size of the clot will be assessed in whole blood samples using a thromboelastometry	Baseline and end of each treatment period (1 month and 3 months)

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Juan J Badimon, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Requena-Ibanez JA, Zafar MU, Ferrandez-Escarabajal M, Escolar G, Santos-Gallego C, Lam D, Badimon JJ. Rationale and Design of the SOTA-THROMBOSIS Trial (ATRU-VI): Antithrombotic Activities of Sotagliflozin Compared With Empagliflozin. J Cardiovasc Pharmacol. 2025 Nov 1;86(5):458-462. doi: 10.1097/FJC.0000000000001747.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2025
• Primary Completion (Actual): February 10, 2026
• Study Completion (Actual): February 10, 2026

Study Registration Dates

• First Submitted: September 19, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: SGLT2; Heart failure; Thrombosis; Platelets; SGLT1/2
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Embolism and Thrombosis; Heart Failure; Thrombosis; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; empagliflozin
• Other Study ID Numbers: STUDY-24-00304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No