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

Phase 4
Recruiting
Conditions
Heart Failure With Preserved Ejection Fraction
Interventions
Drug: Placebo
Registration Number
NCT05562063
Lead Sponsor
Juan Badimon
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboDaily administration of placebo (2 tablet identical in appearance and color to sotagliflozin tablets, orally, once a day) for 6 months.
SotagliflozinSotagliflozinDaily administration of sotagliflozin (2x200 mg, orally, once a day) for 6 months.
Primary Outcome Measures
NameTimeMethod
Changes in Left Ventricular mass in CMRIBaseline and 6 months

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

Secondary Outcome Measures
NameTimeMethod
Changes in Left Ventricular end-systolic volumeBaseline and 6 months

Changes in left ventricular end-systolic volume (LVESV) in CMRI at 6 months compared to baseline

Changes in Left Ventricular end-diastolic volumeBaseline and 6 months

Changes in left ventricular end-diastolic volume (LVEDV) in CMRI at 6 months compared to baseline

Changes in extracellular volume (ECV)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

Changes 6 minute walk testBaseline 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

Changes in Left atrial volume indexBaseline and 6 months

Changes in Left atrial volume index measured by CMRI at 6 months compared to baseline

Changes in Peak oxygen consumption (peakVO2)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

Changes in The Kansas City Cardiomyopathy Questionnaire (KCCQ)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.

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

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