Sotagliflozin in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients

NCT05562063 | Completed Phase 4 FDA Drug

• 1 other identifier: GCO-22-0574
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The clinical benefits of the dual Sodium-Glucose cotransporter (SGLT) 1 and 2-inhibition have recently been reported in two clinical trials. The SOLOIST reported the benefits of sotagliflozin in Type-2 Diabetes Mellitus (T2DM) patients hospitalized for worsening of Heart Failure (HF), while the SCORED involved T2DM patients with Chronic Kidney Disease (CKD). It is worth noting that not only did the event curves separate within the first week post-treatment, but the effects of sotagliflozin on HF-related outcomes were observed regardless of Left Ventricular Ejection Fraction (LVEF) values and did not seem to attenuate with increasing LVEF as seen with empagliflozin and sacubitril/valsartan. Despite the favorable outcomes, the mechanism(s) of action through which sotagliflozin exerts these benefits remains unclear. The present study aims to investigate the potential (non-glucose dependent) "cardio-renal" pleiotropic effects of sotagliflozin in a mechanistic, randomized, double blind, placebo-control trial in HF patients with preserved ejection fraction (HFpEF). Comparisons between treatment groups will be made using cardiac MRI, CPET, 6-MWT and KCCQ-12.

Conditions

Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Changes in Left Ventricular mass in CMRI

  Changes in Left Ventricular (LV) mass at 6 months compared to baseline

  Baseline and 6 months

Secondary Outcomes (7)

• Changes in Left Ventricular end-systolic volume

  Baseline and 6 months

• Changes in Left Ventricular end-diastolic volume

  Baseline and 6 months

• Changes in extracellular volume (ECV)

  Baseline and 6 months

• Changes in Left atrial volume index

  Baseline and 6 months

• Changes in Peak oxygen consumption (peakVO2)

  Baseline and 6 months

Study Arms (2)

Sotagliflozin

EXPERIMENTAL

Daily administration of sotagliflozin (2x200 mg, orally, once a day) for 6 months.

Drug: Sotagliflozin

Placebo

PLACEBO COMPARATOR

Daily administration of placebo (2 tablet identical in appearance and color to sotagliflozin tablets, orally, once a day) for 6 months.

Drug: Placebo

Interventions

Sotagliflozin DRUG

Daily administration of sotagliflozin (2x200 mg, PO, OD) for 6 months.

Sotagliflozin

Placebo DRUG

Matching placebo for 6 months.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory patients age ≥ 18 years
• Written informed consent prior to admission to the trial.
• No diabetes as confirmed by HbA1c \<6.5%, fasting serum glucose \<126 mg/dL, and review of concomitant medications and medical history
• Diagnosis of Heart failure (NYHA II to III)
• LVEF \> 50%
• On medical therapy for heart failure consistent with prevailing cardiovascular guidelines at a stable dose for ≥4 weeks prior to screening, except for diuretics which must have been stable for ≥2 weeks prior to screening
• Women of child-bearing potential must agree to use birth control measures with a failure rate of \<1% per year during the treatment period of the study

You may not qualify if:

• Type 1 and Type 2 diabetes
• Acute coronary syndrome (ACS) or cardiac surgery within the last week.
• Pregnant or lactating women,
• Acute decompensated HF or hospitalized for HF within 1 month from screening visit
• Glomerular Filtration Rate (GFR) \< 25 ml/ min/1.73m2,
• Patients on drugs with potential interaction with sotagliflozin including digoxin, phenytoin, HIV medication and rifampin.
• Receiving SGLT2-I 3-months prior to randomization.
• non-MRI compatible PM or ICD and any other medical or physical condition considered unappropriated by a study physician.

Sponsors & Collaborators

• Juan Badimon: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Interventions

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

Study Officials

• Juan J Badimon

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Carlos G Santos-Gallego, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: September 30, 2022
• Study Start: October 26, 2022
• Primary Completion: June 4, 2025
• Study Completion: June 4, 2025
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)