The main objectives of the study are to demonstrate whether sotagliflozin reduces the composite of CV (cardiovascular) death and HHF (hospitalization for heart failure) as compared to placebo in diabetic patients after admission for WHF (worsening…
ID
Source
Brief title
Condition
- Heart failures
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objectives of this study are:
-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 a left ventricular ejection fraction (LVEF)
<50%, after admission for worsening heart failure (WHF).
-To demonstrate that sotagliflozin reduces CV mortality and morbidity
(composite of CV death or HHF) compared to placebo in hemodynamically stable
patients with T2D and heart failure, irrespective of LVEF.
Secondary outcome
The secondary objectives of this study are:
-To demonstrate that, when compared to placebo, in the total patient
population, sotagliflozin reduces the total number (ie, 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 estimated
glomerular filtration rate (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
-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
patient population.
Background summary
Heart failure (HF) is the most common cause of hospitalization of patients over
the age of 65.
Type 2 diabetes is a growing epidemic worldwide that is associated with a high
incidence of
macrovascular and microvascular complications. The Emerging Risk Factors
Collaboration has recently reported that patients with T2D have a doubled risk
of CV death compared to patients without diabetes. Cardiovascular complications
of diabetes include myocardial infarction (MI), stroke, and HF.
Sotagliflozin (SAR439954) is a dual inhibitor of sodium-glucose co-transporter
1 and 2 (SGLT2 and SGLT1).
Recent data indicate that SGLT2 inhibitors may reduce HF morbidity and
mortality in patients with T2D. These antihyperglycemic agents lower blood
glucose levels, in part, through the inhibition of renal glucose reabsorption
thereby enhancing renal glucose excretion.
Increased renal glucose excretion and therefore osmotic diuresis, one of the
main hypotheses of the mechanism of action on HF, has been seen in patients
with T2D who have received sotagliflozin.
Study objective
The main objectives of the study are to demonstrate whether sotagliflozin
reduces the composite of CV (cardiovascular) death and HHF (hospitalization for
heart failure) as compared to placebo in diabetic patients after admission for
WHF (worsening heart failure).
Study design
This study is a Phase 3, multicenter, randomized, double-blind,
placebo-controlled, parallel-group study in about 4000 hemodynamically stable
patients with T2D who have been admitted to the hospital, a HF unit, infusion
center, or Emergency Department (ED) for WHF with intravascular volume
overload. The study will consist of 3 periods:
* A Screening period (up to 14 days)
* A Randomized, double-blind treatment period that will include an initial
up-titration period
* A Post-treatment period of 14 days
Intervention
Randomized patients will receive sotagliflozin 200 mg or placebo 1 tablet
during the first 2 weeks. At week 3 and beyond sotagliflozin randomized
patients will receive 400 mg and placebo randomized patients will receive 2
tablets.
Study burden and risks
Risk and burdens related to blood collections, study procedures and possible
adverse events of study medication.
Technology Forest Place 8800
The Woodlands TX 77381-1160
US
Technology Forest Place 8800
The Woodlands TX 77381-1160
US
Listed location countries
Age
Inclusion criteria
- patients diagnosed with T2D
- Patient admitted to the hospital or had unplanned HF visit to ED, Heart
Failure Unit, or
infusion center for WHF associated with intravascular volume overload (the
Index Event),
as determined by Investigator AND received treatment with IV diuretics
- Patient had a diagnosis of HF *3 months prior to Screening
- Prior chronic treatment (or prescription) with a loop diuretic (eg,
furosemide, torsemide,
bumetanide) for *30 days prior to the Index Event
- Patients with LVEF <40% should be on beta-blockers and RAAS inhibitors as per
local
guidelines unless contraindicated
- Patient is hemodynamically stable,
- Transitioning from IV to oral diuretics
Exclusion criteria
-Age <18 years (or legal age for the country of participation) or >85 years at
the Screening Visit
-Index Event (admission for worsening HF associated with intravascular volume
overload * see I 02) primarily triggered by pulmonary embolism, cerebrovascular
accident, or acute myocardial infarction (AMI)
-Index Event (admission for WHF * see I 02) for WHF not caused primarily by
intravascular volume overload.
-Hospitalization for index event >2 weeks
-Acute coronary syndromes within 3 months prior to Randomization
-Ejection fraction not assessed at time of Randomization
-End-stage HF
-Cardiac surgery (coronary artery bypass graft), percutaneous coronary
intervention (PCI), implantation of cardiac device (including biventricular
pacemaker), or cardiac mechanical support implantation within 1 month prior to
Randomization or planned during the study
-Hemodynamically significant uncorrected primary cardiac valvular disease
-Significant pulmonary disease contributing substantially to the patients*
dyspnea such as forced expiratory volume in 1 second, or any kind of primary
right heart failure such as primary pulmonary hypertension or recurrent
pulmonary embolism
-Heart failure caused by postpartum cardiomyopathy diagnosed within the past 6
months
-Heart failure from uncorrected thyroid disease, active myocarditis, known
amyloid cardiomyopathy, or hypertrophic obstructive cardiomyopathy
-Obstructive hypertrophic cardiomyopathy
-History of stroke within 3 months prior to Randomization
-History of dialysis within 1 year prior to Randomization
-History of solid organ transplant or inclusion on a
transplant list (if a heart transplant, defined as status 1 transplant)
-Use of any investigational drug(s) for 5 half-lives prior to Screening
-Hypersensitivity to sotagliflozin active substance or to any of the excipients
-Patients who are planning to start a sodium-glucose cotransporter 2 (SGLT2)
inhibitor (other than study drug) during the study.
-Any SGLT2 inhibitor <1 month prior to the Screening Visit, or between
Screening and Randomization
-Patients with respiratory, hepatic, neurological, psychiatric, or active
malignant tumor (except for non-melanoma skin cancers, which are not
exclusionary) or other major systemic disease (including any diseases with
evidence of malabsorption or severe anemia) or patients with short life
expectancy
-Severe kidney disease at the Screening or Randomization
-Any infection requiring intravenous antibiotics and/or with pyrexia (defined
as temperature >38 °C [100.4 °F]) at time of Randomization
-History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 3
months prior to the Screening Visit
-Lower extremity diabetic complications (such as skin ulcers, infection,
osteomyelitis and gangrene) identified during the Screening period, and still
requiring treatment at Randomization
-Pregnant (demonstrated by serum pregnancy test at Screening) or breastfeeding
women
-Women of childbearing potential not willing to use a highly-effective
method(s) of birth control during the study treatment period and the Follow-up
period, or who are unwilling or unable to be tested for pregnancy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2017-003510-16 |
| EudraCT | EUCTR2017-003510-16-NL |
| CCMO | NL64869.100.18 |