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

Phase 3TerminatedNCT03521934

Lexicon Pharmaceuticals1,222 enrolled

Overview

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)

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,222

Conditions

Heart Failure Type 2 Diabetes Mellitus

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Locations (466)

Investigational Site Number 8400128

Alexander City, Alabama, United States

Investigational Site Number 8400109

Cottonwood, Arizona, United States

Investigational Site Number 8400032

Little Rock, Arkansas, United States

Investigational Site Number 8400080

Little Rock, Arkansas, United States

Investigational Site Number 8400075

Bakersfield, California, United States

Outcomes

Primary Outcomes

Number of Total Occurrences of Cardiovascular (CV) Death, Hospitalizations for Heart Failure (HHF) and Urgent Visits for Heart Failure (HF)

Combined endpoint of the total number of occurrences (first and potentially subsequent) of CV death, HHF, and urgent HF visits after randomization. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.

Time frame: Up to 21.9 months

Secondary Outcomes

Total Number of Occurrences of HHF and Urgent HF Visits

Combined endpoint of the total occurrences (first and potentially subsequent) of HHF and urgent HF visits after randomization. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.

Time frame: Up to 21.9 months

Total Number of Deaths From Cardiovascular Causes

Number of events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.

Time frame: Up to 21.9 months

Total Number of Occurrences of CV Death, HHF, Non-fatal Myocardial Infarction and Non-fatal Stroke

Combined endpoint of the total number of occurrences (first and potentially subsequent) of CV death, HHF, non-fatal stroke, and non-fatal myocardial infarction after randomisation. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.

Time frame: Up to 21.9 months

Total Number of Occurrences of HHF, Urgent HF Visit, CV Death, and HF While Hospitalized

Combined endpoint of the total number of occurrences (first and potentially subsequent) after randomisation of HHF, urgent HF visits, CV Death and HF while hospitalised. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.

Time frame: Up to 21.9 months

Total Number of Deaths From Any Cause

Number of events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.

Time frame: Up to 21.9 months

Change From Baseline in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) Scores at Month 4

KCCQ-12 is a 12 question questionnaire, participants completed questionnaire about how heart failure affected their life over the past 2 weeks. The scale has 4 domains: symptom frequency, physical limitation, social limitations and quality of life for a total possible transformed score of 0 to 100 where 100 denotes the highest health status. A positive change from baseline indicates improvement. An analysis of covariance (ANCOVA) model was used for analysis.

Time frame: Baseline to Month 4

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)

eGFR is a test for renal function. A blood sample was collected and was sent to a central laboratory. eGFR was calculated by the Modification of Diet in Renal Disease (MDRD) equation reported as milliliters/minute/1.73 meter squared (mL/min/1.73 m\^2). A mixed model for repeated measures (MMRM) was used for analysis.

Time frame: Baseline up to 21.9 months