Sotagliflozin as Prevention of Anthracycline-Related Cardiotoxicity (SPARTACUS)

SPARTACUS Trial (Sotagliflozin as Prevention of Antracycline-Related Toxicity in Adipose, Cardiac and mUskuloSkeletal Tissues)

This project aims to determine the benefits of the dual SGLT1/2 inhibition as prophylactic treatment to prevent anthracycline-related cardiotoxicity.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma; Chemotherapy; Cardiotoxicity; Anthracycline-induced Cardiotoxicity
• Intervention / Treatment: Drug: Sotagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carlos G Santos-Gallego, MD; Phone Number: 212-241-8484; Email: carlos.santos-gallego@mssm.edu
• Study Contact Backup: Name: Juan Antonio Requena-Ibanez; Phone Number: 212-241-8484; Email: juanantonio.requenaibanez@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Carlos G Santos-Gallego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Patients ≥ 18 years
• Newly diagnosed lymphoma
• Scheduled to receive high-dose anthracycline (cumulative dose ≥ 300 mg/m2)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3

Exclusion Criteria

• Prior anthracycline treatment
• Previous malignancy requiring any chemotherapy or radiotherapy
• Previous treatment with SGLT2i (eg due to T2DM) or SGLT1/2i
• Previous heart failure (HF patients should already be on SGLT2i as per guidelines)
• LVEF<40% (even in the absence of HF):
• Pregnancy or breastfeeding
• Standard contraindication to MRI (claustrophobia, non-MRI compatible devices)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching Placebo	Drug: Placebo; Placebo starting prior to the first scheduled anthracycline infusion
Active Comparator: Sotagliflozin; Sotagliflozin 400mg per day orally	Drug: Sotagliflozin; Sotagliflozin 400mg starting prior to the first scheduled anthracycline infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI	LVEF is a measure of contractility of the heart (strength of contraction). Normal values are between 55-65%. It is the most widely used parameter by physicians worldwide to measure cardiac contractility.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Strain of Left Ventricle (LV)	Longitudinal strain is the deformation of a material per unit length, defined as the ratio of change in length to the original length in the direction of an applied load. It measures how much an object stretches (tensile) or compresses (compressive) along its axis Longitudinal strain is an echocardiographic technique that quantifies the percentage of systolic shortening of the heart muscle from base to apex. It is a highly sensitive indicator of left ventricular function, detecting subclinical, early myocardial dysfunction (e.g., in cardio-oncology) often before the ejection fraction (LVEF) drops. Normal GLS values are typically >18%.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
LVEF by 3D-Echocardiography	LVEF is a measure of contractility of the heart (strength of contraction). Normal values are between 55-65%. It is the most widely used parameter by physicians worldwide to measure cardiac contractility.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
LV Volumes by MRI	LV volumes measure how enlarged the heart is. Chemotherapy destroys cardiac muscle and enlarges the heart (ie. increases LV volumes). The higher the LV volumes, the more damage by chemotherapy.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
LV Mass by MRI	LV mass measures the amount of cardiac muscle. Chemotherapy destroys cardiac muscle. The lower the LV mass, the more damage by chemotherapy.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
LV Longitudinal Strains by MRI	Longitudinal strain is the deformation of a material per unit length, defined as the ratio of change in length to the original length in the direction of an applied load. It measures how much an object stretches (tensile) or compresses (compressive) along its axis Longitudinal strain is an echocardiographic technique that quantifies the percentage of systolic shortening of the heart muscle from base to apex. It is a highly sensitive indicator of left ventricular function, detecting subclinical, early myocardial dysfunction (e.g., in cardio-oncology) often before the ejection fraction (LVEF) drops. Normal GLS values are typically >18%.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
6-Minute Walk Test (6MWT)	The 6MWT assesses endurance and ability to walk over longer distances. The 6MWT was first described as a field test for physical fitness in 1963 and then as a 12-minute walk test in people with chronic bronchitis. The 6MWT was found to perform as well as the 12-minute walk, and is now used to assess the submaximal level of functional performance at a similar level required for daily physical activities.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
NT-ProBNP	NT-ProBNP is a plasma biomarker of cardiac stress, cardiac tension and severity of heart failure. The higher the NT-ProBNP level, the more severe the heart failure induced by chemotherapy.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.
Troponin I	Troponin I is a plasma biomarker of cardiac injury and cardiac damage. The higher the troponin levels, the more cardiac damage induced by chemotherapy.	Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months.

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Carlos G Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: prevention; cardiotoxicity; left ventricular dysfunction; anthracycline; SGLT inhibitors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms; Heart Diseases; Immune System Diseases; Neoplasms by Histologic Type; Chemically-Induced Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Ventricular Dysfunction; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Lymphoma; Ventricular Dysfunction, Left; Cardiotoxicity; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
• Other Study ID Numbers: GCO 25-0408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. For individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link tbd).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No