Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF Trial)

Lexicon Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus; Heart Failure

Treatments: Drug: Placebo; Drug: Sotagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03521934

U1111-1190-7891 (Other Identifier)

EFC15156

2017-003510-16 (EudraCT Number)

Details and patient eligibility

About

Primary Objective:

To compare the effect of sotagliflozin to placebo on the total occurrences of cardiovascular (CV) death, hospitalization for heart failure (HHF), and urgent visit for heart failure (HF) in hemodynamically stable participants after admission for worsening heart failure (WHF)

Secondary Objectives:

To compare the effects of sotagliflozin to placebo on:

• The total occurrences of HHF and urgent visit for HF
• The occurrence of CV death
• The occurrence of all-cause mortality
• The total occurrences of CV death, HHF, urgent visit for HF, non-fatal myocardial infarction (MI), and non-fatal stroke
• Change in Kansas City Cardiomyopathy Questionnaire-12(KCCQ-12) score
• Change in estimated glomerular filtration rate (eGFR)

Full description

The estimated study duration for a given participants will be approximately 3 to 24 months.

Enrollment: 1,222 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 Diabetes Mellitus.
• Admitted to the hospital, or urgent heart failure visit for worsening heart failure.
• Prior diagnosis of heart failure (> 3 months).
• Prior chronic treatment for heart failure with a loop diuretic (eg furosemide, torsemide, bumetanide) for > 30 days.
• Randomized when hemodynamically stable, prior to hospital discharge or within 3 days of discharge.
• Brain natriuretic peptide (BNP) ≥150 picograms per milliliter (pg/mL) (≥450 pg/mL for participants with atrial fibrillation) or N-terminal B-type natriuretic peptide ≥600 pg/mL (≥1800 pg/mL for participants with atrial fibrillation).
• Participants with Left Ventricular Ejection Fraction <40% should be on beta-blockers and renin-angiotensin-aldosterone system (RAAS) inhibitors as per local guidelines unless contraindicated.
• Signed written informed consent.

Exclusion criteria

• Age < 18 years or > 85 years.
• Worsening heart failure attributed to other causes such as pulmonary embolism, stroke, heart attack.
• Cardiac surgery or coronary procedure within 1 month or planned during study.
• Lower extremity complications (such as skin ulcer, infection, osteomyelitis, and gangrene) identified during screening and requiring treatment at randomization.
• Planning to start a sodium-glucose linked transporter-2 (SGLT2) inhibitor during the study.
• Acute coronary syndromes within 3 months prior to Randomization.
• Hemodynamically significant uncorrected primary valvular disease.
• Significant pulmonary disease contributing substantially to the participant's dyspnea.
• End stage Heart Failure.
• History of diabetic ketoacidosis (DKA) or nonketotic hyperosmolar coma within 3 months prior to screening.
• History of stroke within 3 months prior to randomization.
• History of dialysis within 1 year prior to randomization.
• History of solid organ transplant or on a transplant list (if heart transplant, defined as status 1 transplant).
• Severe kidney disease as defined by glomerular filtration rate (eGFR) <30 milliliter per minute per 1.72 meter square (mL/min/1.73 m^2).
• Pregnancy.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,222 participants in 2 patient groups, including a placebo group

Sotagliflozin

Experimental group

Description:

Sotagliflozin 200 mg tablet once daily, with possible up-titration in the first 8 months to 400 mg, for up to 21.2 months.

Treatment:

Drug: Sotagliflozin

Placebo

Placebo Comparator group

Description:

Matching placebo to sotagliflozin 200 mg once daily, with possible up-titration in the first 8 months to matching placebo to sotagliflozin 400 mg, for up to 21.6 months.

Treatment:

Drug: Placebo