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Effect of Ertugliflozin on Cardiac Function in Diabetes (ERTU-GLS)

Primary Purpose

Type2 Diabetes, Heart Failure

Status

Completed

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Ertugliflozin

Placebo

About this trial

This is an interventional treatment trial for Type2 Diabetes focused on measuring type 2 diabetes, heart failure, ertugliflozin, Global longitudinal strain (GLS)

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Seoul National University Bundang Hospita;

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ertugliflozin

Control group

Arm Description

Ertugliflozin 5 mg in addition to their preexisting metformin and/or DPP4 inhibitor

Placebo in addition to their preexisting metformin and/or DPP4 inhibitor

Outcomes

Primary Outcome Measures

Global Longitudinal Strain (GLS)

Change of GLS after 24 weeks' treatment

Secondary Outcome Measures

E/e' ratio

Change of E/e' after 24 weeks' treatment

Ejection fraction (EF)

Change of EF after 24 weeks' treatment

Left ventricle mass

Change of LV mass after 24 weeks' treatment

Glycated hemoglobin

Change of HbA1c mass after 24 weeks' treatment

Body weight

Change of body weight mass after 24 weeks' treatment

Body Fat Mass

Change of body fat mass after 24 weeks' treatment

Full Information

NCT ID

NCT03717194

First Posted

October 22, 2018

Last Updated

August 10, 2023

Sponsor

Soo Lim

Collaborators

MSD Korea Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03717194

Brief Title

Effect of Ertugliflozin on Cardiac Function in Diabetes

Acronym

ERTU-GLS

Official Title

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, to Evaluate the Effect of Ertugliflozin on Cardiac Function in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control and Stage B Heart Failure

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

June 1, 2019 (Actual)

Primary Completion Date

December 31, 2022 (Actual)

Study Completion Date

April 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Soo Lim

Collaborators

MSD Korea Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type2 Diabetes, Heart Failure

Keywords

type 2 diabetes, heart failure, ertugliflozin, Global longitudinal strain (GLS)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

102 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ertugliflozin

Arm Type

Experimental

Arm Description

Ertugliflozin 5 mg in addition to their preexisting metformin and/or DPP4 inhibitor

Arm Title

Control group

Arm Type

Placebo Comparator

Arm Description

Placebo in addition to their preexisting metformin and/or DPP4 inhibitor

Intervention Type

Drug

Intervention Name(s)

Ertugliflozin

Other Intervention Name(s)

Steglatro

Intervention Description

Ertugliflozin as add-on to Metformin and/or DPP4 inhibitors in patients with inadequately controlled type 2 diabetes

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo as add-on to Metformin and/or DPP4 inhibitors in patients with inadequately controlled type 2 diabetes

Primary Outcome Measure Information:

Title

Global Longitudinal Strain (GLS)

Description

Change of GLS after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

Secondary Outcome Measure Information:

Title

E/e' ratio

Description

Change of E/e' after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

Title

Ejection fraction (EF)

Description

Change of EF after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

Title

Left ventricle mass

Description

Change of LV mass after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

Title

Glycated hemoglobin

Description

Change of HbA1c mass after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

Title

Body weight

Description

Change of body weight mass after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

Title

Body Fat Mass

Description

Change of body fat mass after 24 weeks' treatment

Time Frame

Baseline, week 12, week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Soo Lim, MD, PhD

Organizational Affiliation

Seoul National University Bundang Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seoul National University Bundang Hospita;

City

Seongnam-si

State/Province

Gyeonggi-do

ZIP/Postal Code

13620

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

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26378978

Citation

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Citation

Krishnasamy R, Isbel NM, Hawley CM, Pascoe EM, Burrage M, Leano R, Haluska BA, Marwick TH, Stanton T. Left Ventricular Global Longitudinal Strain (GLS) Is a Superior Predictor of All-Cause and Cardiovascular Mortality When Compared to Ejection Fraction in Advanced Chronic Kidney Disease. PLoS One. 2015 May 15;10(5):e0127044. doi: 10.1371/journal.pone.0127044. eCollection 2015.

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Effect of Ertugliflozin on Cardiac Function in Diabetes

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