Clinical trial NCT05562063: Sotagliflozin in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients
Official title: SOTA-P-CARDIA Trial: A Randomized Trial of Sotagliflozin in HFpEF Patients Without Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure With Preserved Ejection Fraction
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2022-09-30
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Changes in Left Ventricular mass in CMRI
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Changes in Left Ventricular end-systolic volume
timeFrame: Baseline and 6 months
measure: Changes in Left Ventricular end-diastolic volume
timeFrame: Baseline and 6 months
measure: Changes in extracellular volume (ECV)
timeFrame: Baseline and 6 months
measure: Changes in Left atrial volume index
timeFrame: Baseline and 6 months
measure: Changes in Peak oxygen consumption (peakVO2)
timeFrame: Baseline and 6 months
measure: Changes 6 minute walk test
timeFrame: Baseline and 6 months
measure: Changes in The Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Juan J Badimon
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Carlos G Santos-Gallego, MD
role: PRINCIPAL_INVESTIGATOR
References: