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Effect of Ertugliflozin on Cardiac Function in Diabetes

Phase 3
Completed
Conditions
Heart Failure
Type2 Diabetes
Interventions
Drug: Placebo
Registration Number
NCT03717194
Lead Sponsor
Soo Lim
Brief Summary

The aim of this study is to investigate the beneficial role of ertugliflozin, a new SGLT2 inhibitor, in cardiac function via measuring GLS as well as other hemodynamic factors using echocardiogram in patients with T2D and HF, who are not controlled with oral antidiabetic medications including DPP4 inhibitors.

Detailed Description

This study is a phase 3, randomized, double-blind, active-competitor, parallel-group study that is anticipated to enroll 120 patients. Patients taking metformin and/or DPP4 inhibitors as per local label for ≥12 weeks without a dose adjustment before enrollment will be eligible for screening. All patients will have a screening period comprised of an up to 2-week screening phase prior to randomization. In order to qualify for randomization, patients must demonstrate compliance based upon pill count (80%) and discretion of the investigators during the Run-in phase.

Glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) will be masked to patients after randomization. To prevent partial unblinding, urinary glucose excretion (UGE) results will be masked to patients. Urine glucose, albumin, calcium, and creatinine will be measured separately on-site visits.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
Inclusion Criteria
  • Patients with T2D taking oral antidiabetic medications (metformin and/or DPP4 inhibitors) except SGLT2 inhibitors for at least 12 weeks without a dose adjustment before enrollment.
  • eGFR ≥ 45 mL/min/1.73 m2.
  • Stage B HF identified on the basis of either structural or functional markers.
Exclusion Criteria
  • Type 1 diabetes mellitus
  • At the time of screening age <20 years
  • HbA1c <7% or HbA1c >9.5% at Screening
  • FPG >15 mmol/L (270 mg/dL) measured by the laboratory at Screening (Visit 1), and confirmed (>15 mmol/L [>270 mg/dL]) by a repeat test before randomization
  • Treated with insulin and/or GLP-1R agonist within 12 weeks preceding the Screening Visit.
  • Women of childbearing potential with no effective contraceptive method
  • History of gastric surgery including history of gastric banding within 3 years before the Screening Visit
  • History of diabetic ketoacidosis or nonketotic hyperosmolar coma prior to the Screening Visit
  • Mean blood pressure after 3 separate measurements >180 mmHg in systolic blood pressure (SBP) or >95 mmHg in diastolic blood pressure (DBP)
  • Patients with current or prior symptoms of HF.
  • Patients with severe anemia, severe respiratory, hepatic, neurological, psychiatric disorders or active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult
  • Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN)
  • Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome)
  • Use of systemic glucocorticoids (excluding topical or ophthalmic, application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit
  • Patient who has taken other investigational drugs or prohibited therapy for this study within 3 months

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control groupPlaceboPlacebo in addition to their preexisting metformin and/or DPP4 inhibitor
ErtugliflozinErtugliflozinErtugliflozin 5 mg in addition to their preexisting metformin and/or DPP4 inhibitor
Primary Outcome Measures
NameTimeMethod
Left Ventricular Global Longitudinal Strain (LVGLS)Baseline, Week 24

Change in LVGLS after 24 weeks of treatment

Secondary Outcome Measures
NameTimeMethod
Left Ventricular End-diastolic Volume (LVEDV)Baseline, Week 24

Change in LVEDV after 24 weeks of treatment

Left Atrium Ventricular Index (LAVI)Baseline, Week 24

Change in LVVI after 24 weeks of treatment

Left Ventricular Mass Index (LVMI)Baseline, Week 24

Change in LVMI after 24 weeks of treatment

Left Ventricular Ejection Fraction (LVEF)Baseline, Week 24

Change in LVEF after 24 weeks of treatment

E/e' RatioBaseline, Week 24

Change in E/e' ratio after 24 weeks of treatment

Trial Locations

Locations (1)

Seoul National University Bundang Hospita;

🇰🇷

Seongnam-si, Gyeonggi-do, Korea, Republic of

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