Antithrombotic Activities of Sotagliflozin vs. Empagliflozin

NCT06618976 | Completed Phase 4 FDA Drug

• 1 other identifier: STUDY-24-00304
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Thrombosis

Keywords

Thrombosis; Platelets; Heart failure; SGLT2; SGLT1/2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Platelet aggregation

  Baseline and end of each treatment period (1 month and 3 months)

• Clot formation size

  Baseline and end of each treatment period (1 month and 3 months)

Study Arms (2)

Sotagliflozin then Empagliflozin

OTHER

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; Drug: Empagliflozin

Empagliflozin then Sotagliflozin

OTHER

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; Drug: Empagliflozin

Interventions

Sotagliflozin DRUG

Sotagliflozin 400 mg, P.O. once daily for 1 month.

Empagliflozin then Sotagliflozin; Sotagliflozin then Empagliflozin

Empagliflozin DRUG

Empagliflozin 10 mg, P.O. once daily for 1 month.

Empagliflozin then Sotagliflozin; Sotagliflozin then Empagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• 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.

  PMID: 40748666 DERIVED

MeSH Terms

Conditions

Thrombosis; Heart Failure

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; empagliflozin

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Study Officials

• Juan J Badimon

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: October 1, 2024
• Study Start: February 25, 2025
• Primary Completion: February 10, 2026
• Study Completion: February 10, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)