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

• ClinicalTrials.gov Identifier: NCT05562063
• Recruitment Status: Recruiting
• First Posted: September 30, 2022
• Last Update Posted: August 21, 2023
• Sponsor: Juan Badimon
• Information provided by (Responsible Party): Juan Badimon, Icahn School of Medicine at Mount Sinai

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Heart Failure With Preserved Ejection Fraction	Drug: Sotagliflozin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: SOTA-P-CARDIA Trial: A Randomized Trial of Sotagliflozin in HFpEF Patients Without Diabetes
• Actual Study Start Date: October 26, 2022
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sotagliflozin; Daily administration of sotagliflozin (2x200 mg, orally, once a day) for 6 months.	Drug: Sotagliflozin; Daily administration of sotagliflozin (2x200 mg, PO, OD) for 6 months.
Placebo Comparator: Placebo; Daily administration of placebo (2 tablet identical in appearance and color to sotagliflozin tablets, orally, once a day) for 6 months.	Drug: Placebo; Matching placebo for 6 months.

Outcome Measures

Primary Outcome Measures :

1. Changes in Left Ventricular mass in CMRI [ Time Frame: Baseline and 6 months ]
   Changes in Left Ventricular (LV) mass at 6 months compared to baseline

Secondary Outcome Measures :

1. Changes in Left Ventricular end-systolic volume [ Time Frame: Baseline and 6 months ]
   Changes in left ventricular end-systolic volume (LVESV) in CMRI at 6 months compared to baseline
2. Changes in Left Ventricular end-diastolic volume [ Time Frame: Baseline and 6 months ]
   Changes in left ventricular end-diastolic volume (LVEDV) in CMRI at 6 months compared to baseline
3. Changes in extracellular volume (ECV) [ Time Frame: Baseline and 6 months ]
   Changes in extracellular volume (ECV) to assess Left Ventricular interstitial myocardial fibrosis as quantified using T1 mapping at 6 months compared to baseline
4. Changes in Left atrial volume index [ Time Frame: Baseline and 6 months ]
   Changes in Left atrial volume index measured by CMRI at 6 months compared to baseline
5. Changes in Peak oxygen consumption (peakVO2) [ Time Frame: Baseline and 6 months ]
   Changes in exercise capacity as assessed by peak oxygen consumption in Cardiopulmonary exercise test (CPET) at 6 months compared to baseline
6. Changes 6 minute walk test [ Time Frame: Baseline and 6 months ]
   Changes in exercise tolerance as assessed by 6 minute walk test, or the distance covered over a time of 6 minutes, at 6 months compared to baseline
7. Changes in The Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: Baseline and 6 months ]

   Changes in The KCCQ at 6 months compared to baseline. The KCCQ is the most widely used instrument to evaluate quality of life in Heart Failure (HF).

   The KCCQ is a 12-item self-administered questionnaire used to measure the patient's perception of their health status. The KCCQ is a disease-specific health status instrument composed of 12 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Full scale range is from 0 to 100; higher scores reflect better health status.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: patients should meet all of the following criteria

• 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

Exclusion Criteria:

• 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.

Contacts and Locations

Contacts

Contact: Juan J Badimon; (212) 241-8484; Juan.Badimon@mssm.edu

Contact: Carlos G Santos-Gallego, MD; 212-241-8484; carlos.santos-gallego@mssm.edu

Locations

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Sponsors and Collaborators

Juan Badimon

Investigators

• Principal Investigator: Juan J Badimon; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Carlos G Santos-Gallego, MD; Icahn School of Medicine at Mount Sinai

More Information

• Responsible Party: Juan Badimon, Professor of Medicine, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT05562063
• Other Study ID Numbers: GCO-22-0574
• First Posted: September 30, 2022
• Last Update Posted: August 21, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Undecided: It is not yet known if there will be a plan to make IPD available.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs