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

Juan Badimon

Status and phase: Completed; Phase 4

Conditions: Heart Failure With Preserved Ejection Fraction

Treatments: Drug: Sotagliflozin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05562063

GCO-22-0574

Details and patient eligibility

About

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.

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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88 participants in 2 patient groups, including a placebo group

Sotagliflozin

Experimental group

Description:

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

Treatment:

Drug: Sotagliflozin

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo