Effect of Ertugliflozin on Cardiac Function in Diabetes

NCT03717194 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: B-2018-498-002
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes; Heart Failure

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Global Longitudinal Strain (LVGLS)

  Change in LVGLS after 24 weeks of treatment

  Baseline, Week 24

Secondary Outcomes (5)

• Left Ventricular Mass Index (LVMI)

  Baseline, Week 24

• Left Ventricular Ejection Fraction (LVEF)

  Baseline, Week 24

• E/e' Ratio

  Baseline, Week 24

• Left Atrium Ventricular Index (LAVI)

  Baseline, Week 24

• Left Ventricular End-diastolic Volume (LVEDV)

  Baseline, Week 24

Other Outcomes (4)

• N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)

  Baseline, Week 24

• Troponin-T

  Baseline, Week 24

• Angiotensin-converting Enzyme 2 (ACE2)

  Baseline, Week 24

Study Arms (2)

Ertugliflozin

EXPERIMENTAL

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

Drug: Ertugliflozin

Control group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ertugliflozin DRUG

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

Also known as: Steglatro

Ertugliflozin

Placebo DRUG

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

Control group

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Soo Lim: lead
• MSD Korea Ltd.: collaborator

Study Sites (1)

Seoul National University Bundang Hospita;

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Related Publications (13)

• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

  PMID: 26378978 BACKGROUND

• Neal B, Perkovic V, Matthews DR. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Nov 23;377(21):2099. doi: 10.1056/NEJMc1712572. No abstract available.

  PMID: 29166232 BACKGROUND

• 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.

  PMID: 25978372 BACKGROUND

• Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Jacobs AK, Hiratzka LF, Russell RO, Smith SC; American College of Cardiology; American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. J Heart Lung Transplant. 2002 Feb;21(2):189-203. doi: 10.1016/s1053-2498(01)00776-8. No abstract available.

  PMID: 11834347 BACKGROUND

• Kosmala W, Jellis CL, Marwick TH. Exercise limitation associated with asymptomatic left ventricular impairment: analogy with stage B heart failure. J Am Coll Cardiol. 2015 Jan 27;65(3):257-66. doi: 10.1016/j.jacc.2014.10.044. Epub 2014 Dec 19.

  PMID: 25533754 BACKGROUND

• Kramer DG, Trikalinos TA, Kent DM, Antonopoulos GV, Konstam MA, Udelson JE. Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a meta-analytic approach. J Am Coll Cardiol. 2010 Jul 27;56(5):392-406. doi: 10.1016/j.jacc.2010.05.011.

  PMID: 20650361 BACKGROUND

• Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986 Feb 15;57(6):450-8. doi: 10.1016/0002-9149(86)90771-x.

  PMID: 2936235 BACKGROUND

• Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005 Dec;18(12):1440-63. doi: 10.1016/j.echo.2005.10.005. No abstract available.

  PMID: 16376782 BACKGROUND

• Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009 Feb;22(2):107-33. doi: 10.1016/j.echo.2008.11.023. No abstract available.

  PMID: 19187853 BACKGROUND

• Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr. 2004 Jun;17(6):630-3. doi: 10.1016/j.echo.2004.02.011.

  PMID: 15163933 BACKGROUND

• Lima MSM, Villarraga HR, Abduch MCD, Lima MF, Cruz CBBV, Sbano JCN, Voos MC, Mathias W Junior, Tsutsui JM. Global Longitudinal Strain or Left Ventricular Twist and Torsion? Which Correlates Best with Ejection Fraction? Arq Bras Cardiol. 2017 Jul;109(1):23-29. doi: 10.5935/abc.20170085. Epub 2017 Jun 29.

  PMID: 28678927 BACKGROUND

• Medvedofsky D, Kebed K, Laffin L, Stone J, Addetia K, Lang RM, Mor-Avi V. Reproducibility and experience dependence of echocardiographic indices of left ventricular function: Side-by-side comparison of global longitudinal strain and ejection fraction. Echocardiography. 2017 Mar;34(3):365-370. doi: 10.1111/echo.13446. Epub 2017 Feb 9.

  PMID: 28185312 BACKGROUND

• Lim S, Bae JH, Oh H, Hwang IC, Yoon YE, Cho GY. Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial. Cardiovasc Diabetol. 2024 Oct 22;23(1):373. doi: 10.1186/s12933-024-02463-0.

  PMID: 39438942 DERIVED

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus, Type 2

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Soo Lim
• Organization: Seoul National University Bundang Hospital

limsoo@snu.ac.kr

+82-31-787-7035

Study Officials

• Soo Lim, MD, PhD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 24, 2018
• Study Start: June 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: April 30, 2023
• Last Updated: November 20, 2024
• Results First Posted: November 20, 2024

Record last verified: 2024-10

Locations

KR (1)