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

Study Description

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Brief Summary:

Primary Objective:

• To demonstrate that sotagliflozin reduces cardiovascular (CV) mortality and morbidity (composite of CV death or hospitalization for heart failure [HHF]) compared to placebo in hemodynamically stable patients with type 2 diabetes (T2D) and heart failure (HF) with left ventricular ejection fraction (LVEF) <50%, after admission for worsening heart failure (WHF).
• To demonstrate that sotagliflozin reduces cardiovascular (CV) mortality and morbidity (composite of CV death or hospitalization for heart failure [HHF]) compared to placebo in hemodynamically stable patients with T2D and HF irrespective of LVEF after admission for WHF.

Secondary Objectives:

• To demonstrate that, when compared to placebo in the toal patient population, sotagliflozin reduces the total number (i.e., including recurrent events) of the following clinical events:
• Cardiovascular death, HHF or urgent HF visit.
• To demonstrate that, when compared to placebo, sotagliflozin reduces:
• The composite of positively adjudicated sustained ≥50% decrease in eGFR, chronic dialysis, renal transplant or positively adjudicated sustained eGFR <15 mL/min/1.73 m2 in the total patient population.
• Cardiovascular death in patients with LVEF < 50%.
• Cardiovascular death in the total patient population.
• All-cause mortality in patients with LVEF < 50%.
• All cause mortality in the total patient population.
• To demonstrate the safety and tolerability of sotagliflozin in the total population in this study.

Condition or disease	Intervention/treatment	Phase
Heart Failure-Type 2 Diabetes Mellitus	Drug: Sotagliflozin (SAR439954); Drug: Placebo	Phase 3

Detailed Description:

The estimated study duration for a given patient will be approximately 3 to 32 months.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	4000 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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
Actual Study Start Date :	June 11, 2018
Estimated Primary Completion Date :	January 2021
Estimated Study Completion Date :	January 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Sotagliflozin; Sotagliflozin dose 1, once daily with possible uptitration in the first 8 months to dose 2	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral
Placebo Comparator: Placebo; Placebo dose 1, once daily with possible uptitration in the first 8 months to dose 2	Drug: Placebo; Pharmaceutical form: tablet Route of administration: oral

Outcome Measures

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Primary Outcome Measures :

1. Cardiovascular (CV) death or hospitalization for heart failure (HHF) [ Time Frame: Baseline to approximately 32 months ]
   Time to first occurrence of either cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with left ventricular ejection fraction (LVEF) <50%
2. Cardiovascular (CV) death or hospitalization for heart failure (HHF) [ Time Frame: Baseline to approximately 32 months ]
   Time to first occurrence of either CV death or HHF in the total patient population -

Secondary Outcome Measures :

1. Total number of heart failure events [ Time Frame: Baseline to approximately 32 months ]
   Total number (i.e., including recurrent events) of the following clinical events in the total patient population: Cardiovascular death, Hospitalization for heart failure, Urgent HF visit
2. Time to first composite renal event [ Time Frame: Baseline to approximately 32 months ]
   Time to first occurrence of the composite of positively adjudicated sustained ≥50% decrease in eGFR from Baseline (for ≥30 days), chronic dialysis, renal transplant, or positively adjudicated sustained eGFR <15 mL/min/1.73 m2 (for ≥30 days) in the total patient population.
3. Cardiovascular (CV) death [ Time Frame: Baseline to approximately 32 months ]
   Time to CV death in patients with LVEF <50%
4. Cardiovascular (CV) death [ Time Frame: Baseline to approximately 32 months ]
   Time to CV death in the total patient population
5. All cause mortality [ Time Frame: Baseline to approximately 32 months ]
   Time to all-cause mortality in patients with LVEF <50%
6. All cause mortality [ Time Frame: Baseline to approximately 32 months ]
   Time to all-cause mortality in the total patient population

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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 pg/mL (≥450 pg/mL for patients with atrial fibrillation) or N-terminal B-type natriuretic peptide ≥600 pg/mL (≥1800 pg/mL for patients with atrial fibrillation).
• Patients 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 patient'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 mL/min/1.73 m².
• Pregnancy.

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

Contacts and Locations

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Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada)	800-633-1610 ext 1 then #	Contact-Us@sanofi.com

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Sponsors and Collaborators

Sanofi

Investigators

Study Director:	Clinical Sciences & Operations	Sanofi

More Information

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Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT03521934 History of Changes
Other Study ID Numbers:	EFC15156; 2017-003510-16 ( EudraCT Number ); U1111-1190-7891 ( Other Identifier: UTN )
First Posted:	May 10, 2018
Last Update Posted:	February 18, 2019
Last Verified:	February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Heart Failure; Glucose Metabolism Disorders	Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases