Trial Purpose and Description
We propose a small, mechanistically focused, study evaluate the existence and probe the mechanisms underlying cardio-renal effects of sotagliflozin in patients with heart failure. Importantly, the major goals of the project will be to determine if similar cardio-renal effects are seen between sotagliflozin and empagliflozin. We propose a 40 patient randomized double blind crossover study with stable heart failure and type II diabetes whom are chronically receiving loop diuretics. The crossover design was chosen to maximize power to see significant differences since cardio-renal parameters often have a large inter-subject variability thus allowing each patient to serve as their own control will maximize study efficiency.
Ages: 18 years and older
Inclusion criteria :
- Capable of providing written informed consent.
- 18 years of age or older.
- Patient admitted to the hospital for Congestive Heart Failure (CHF) (Index Hospitalization), defined by:
- Presence of ≥2 of the following clinical signs and symptoms of congestion: jugular venous distension, pitting edema in lower extremities greater than trace, dyspnea, rales heard on auscultation, radiographic pulmonary congestion, and
- Requiring treatment with IV diuretics (≥2 bolus doses or continuous infusion).
- Prior diagnosis of Heart Failure (ie, prior to most recent episode of CHF decompensation leading to Index Hospitalization), defined as follows (based on appropriate supportive documentation):
- Hospitalization for Congestive Heart Failure within 12 months prior to Index hospitalization, OR
- Prior Diagnosis of Heart Failure (HF) with chronic treatment with a loop diuretic for at least 30 days.
- Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m^2 at the screening or randomization visit by the 4 variable Modification of Diet in Renal Disease (MDRD) equation.
- Female subject must use a double contraception method during the study including a highly effective method of birth control, except if she has undergone sterilization at least 3 months earlier or is postmenopausal.
- Male participants must use 2 forms of birth control during the study and refrain from donating sperm up to 90 days after the day of last dose. If the patient has a female partner of childbearing potential, the patient must wear a condom and female partner must use at least 1 highly effective method of birth control.
- Transitioning from IV to oral diuretics defined as:
- IV diuretic has been discontinued;
- Oral diuretic treatment has been prescribed or administered.
- Hemodynamically stable, defined as:
- Systolic Blood Pressure >100 mmHg;
- No requirement for IV inotropic therapy or IV vasodilators (except for nitrates) within 3 days of randomization.
- History of Type 1 diabetes mellitus.
- Appears unlikely or unable to participate in the required study procedures, as assessed by the study.
- Investigator, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease).
- Current hospitalization for Worsening HF that is clearly and primarily triggered by causes such as tachyarrhythmia (example: sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response > 130 beats per minute), acute coronary syndrome, pulmonary embolism, cerebrovascular accident, heart valve disorders, as determined by the Investigator.
- Clinically significant myocardial infarction (MI) within past 1 month as determined by Investigator and with objective evidence from ECG, and/or cardiac imaging and/or coronary angiography. Small isolated elevations in troponin that often accompany HF hospitalization are not an exclusion.
- Recent (within 30 days prior to screening) or planned cardiac intervention during the study that may lead to improvement of cardiac function. This includes but is not limited to: coronary revascularization (percutaneous coronary intervention (PCA), coronary artery bypass graft (CABG), biventricular pacemaker insertion, heart valve repair or replacement, cardiac mechanical support implantation, such as implantable cardioverter defibrillator insertion, and other cardiac operations).
- Current use of or recent suspension of digoxin therapy with high levels of digoxin (level should be obtained and must be <1.2 ng/mL) at screening.
- History of heart or kidney transplant.
- Diagnosis of hypertrophic obstructive cardiomyopathy.
- End-stage HF defined as requiring left ventricular assist device insertion, intra-aortic balloon placement (IABP), or any type of mechanical support during the study period.
- Pregnancy (demonstrated by serum pregnancy test at screening), breast-feeding, or inability or refusal to undergo pregnancy testing.
- Use of any investigational drug(s) or prohibited therapy or sodium-glucose co-transporter 2 (SGLT2) inhibitor within 3 months or 5 half-lives prior to screening, whichever is longer.
- Patients with severe respiratory (requiring ≥2L continuous O2 therapy), moderate and severe hepatic, neurological, psychiatric, active malignant tumor or other major systemic disease (including any diseases with evidence of malabsorption), making implementation of the protocol and/or the interpretation of the study results difficult.
- Known allergies, hypersensitivity, or intolerance to sotagliflozin or any inactive component of sotagliflozin or placebo (ie, microcrystalline cellulose, croscarmellose sodium [disintegrant], talc, silicon dioxide, and magnesium stearate [non-bovine]), unless the reaction is deemed irrelevant to the study by the PI.
- Laboratory findings at the Screening Visit:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range (ULN) (1 repeat lab allowed);
- Total bilirubin >1.7 times the ULN (except in case of Gilbert's syndrome) (1 repeat lab allowed);
- Amylase and/or lipase > 3 times the ULN.
- Current or planned daily use of a high dose thiazide diuretic (ex: ≥5mg of metolazone or ≥50mg of hydrochlorothiazide) during the study period.
- Patients with a genitourinary tract infection at time of randomization.
- History of diabetic ketoacidosis or non-ketotic hyperosmolar coma within 3 months prior to the screening visit.
- Patients who are planning to start an SGLT2 inhibitor during the study.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Dates: 12/04/2017 - 07/31/2019
Last Updated: 01/02/2018
Study HIC#: 2000020192