Brief Summary
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)
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)
Brief Title
Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF Trial)
Detailed Description
The estimated study duration for a given participants will be approximately 3 to 24 months.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Heart Failure
Type 2 Diabetes Mellitus
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
85 Years
Minimum Age
18 Years
NCT Id
NCT03521934
Org Class
Industry
Org Full Name
Lexicon Pharmaceuticals
Org Study Id
EFC15156
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Effects of Sotagliflozin on Clinical Outcomes in Hemodynamically Stable Patients With Type 2 Diabetes POST Worsening Heart Failure
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Total Occurrences of Cardiovascular (CV) Death, Hospitalizations for Heart Failure (HHF) and Urgent Visits for Heart Failure (HF)
Outcome Time Frame
Up to 21.9 months
Secondary Ids
Secondary Id
2017-003510-16
Secondary Id
U1111-1190-7891
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 21.9 months
Outcome Measure
Total Number of Occurrences of HHF and Urgent HF Visits
Outcome Description
Number of events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.
Outcome Time Frame
Up to 21.9 months
Outcome Measure
Total Number of Deaths From Cardiovascular Causes
Outcome Description
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.
Outcome Time Frame
Up to 21.9 months
Outcome Measure
Total Number of Occurrences of CV Death, HHF, Non-fatal Myocardial Infarction and Non-fatal Stroke
Outcome Description
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.
Outcome Time Frame
Up to 21.9 months
Outcome Measure
Total Number of Occurrences of HHF, Urgent HF Visit, CV Death, and HF While Hospitalized
Outcome Description
Number of events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up.
Outcome Time Frame
Up to 21.9 months
Outcome Measure
Total Number of Deaths From Any Cause
Outcome Description
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.
Outcome Time Frame
Baseline to Month 4
Outcome Measure
Change From Baseline in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) Scores at Month 4
Outcome Description
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.
Outcome Time Frame
Baseline up to 21.9 months
Outcome Measure
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
85
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Snehal Patel
Investigator Email
snepatel@montefiore.org
Investigator Phone