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

• Register: EUCTR
• Last refreshed on: 6 October 2020
• Main ID: EUCTR2017-003510-16-SE
• Date of registration: 16/03/2018
• Prospective Registration: Yes
• Primary sponsor: Lexicon Pharmaceuticals, Inc.
• Public title: Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabètes Post Worsening Heart Failure (SOLOIST-WHF Trial)
• Scientific 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 - SOLOIST-WHF
• Date of first enrolment: 07/05/2018
• Target sample size: 6667
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003510-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Executive Director, Clinical Ops
• Affiliation: Lexicon Pharmaceuticals, Inc.

• Name: Executive Director, Clinical Ops
• Affiliation: Lexicon Pharmaceuticals, Inc.

Key inclusion & exclusion 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 Nterminal 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 RAAS (reninangiotensin-aldosterone system) inhibitors as per local guidelines unless contraindicated.
-Signed written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2667

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 eGFR (glomerular filtration rate) <30 mL/min/1.73 m².
-Pregnancy.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cardiovascular diseases
MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
MedDRA version: 21.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Sotagliflozin
Product Code: SAR439954
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOTAGLIFLOZIN
CAS Number: 1018899-04-1
Current Sponsor code: SAR439954
Other descriptive name: LX4211, LX-4211, LP-802034
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): - Time to first occurrence of either cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with left ventricular ejection fraction (LVEF) <50%
- Time to first occurrence of either CV death or HHF in the total patient population

Timepoint(s) of evaluation of this end point: Baseline to approximately 32 months

Main 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 Objective: -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 demostrate 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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to approximately 32 months

Secondary end point(s): 1. 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 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. Time to CV death in patients with LVEF <50%
4. Time to CV death in the total patient population
5. Time to all-cause mortality in patients with LVEF <50%
6. Time to all-cause mortality in the total patient population

Secondary ID(s)

EFC15156

Source(s) of Monetary Support

Lexicon Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 02/05/2018
Contact: