Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes

NCT02998970 | Unknown Phase 4 DMC

• 1 other identifier: REB# 15-402
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects of Empagliflozin on cardiac structure, function and circulating biomarkers in patients with Type II diabetes. Empagliflozin (anti-hyperglycemic agent), approved by Health Canada and the FDA for the treatment of Type II diabetes, demonstrated a reduction in cardiovascular deaths and heart failure from a previous post-marketing clinical trial. The use of empagliflozin to treat patients with diabetes and heart disease has been approved by Health Canada. However, the process by which it may give this beneficial effect remains unclear and needs further investigation. Therefore, the aim of this study is to provide a fundamental understanding of the mechanistic basis by which Empagliflozin could provide its potential cardio-protective effects by employing the use of Cardiac Magnetic Resonance Imaging (CMRI).

Conditions

Diabetes; Cardiovascular Disease

Keywords

Cardiovascular Disease; Type 2 Diabetes; Cardiac Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Left Ventricular (LV) mass Changes

  Changes in Left Ventricular (LV) mass (indexed to BSA) at 6 months in patients with Type 2 diabetes who receive empagliflozin vs. placebo. This will be measured using CMRI.

  6 months

Secondary Outcomes (8)

• LV end-diastolic volume

  6 months

• End-systolic volume (indexed to BSA)

  6 months

• Left Ventricular Ejection Fraction (LVEF)

  6 months

• Regional LV diastolic function

  6 months

• Regional LV systolic function

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The placebo group acts as a control group. This is in order to objectively isolate empagliflozin's effect on cardiac structure and function as determined by CMR imaging.

Drug: Placebo

Empagliflozin

ACTIVE COMPARATOR

The study medication (Jardiance) is the only diabetes medication to show a significant reduction in both cardiovascular risk and cardiovascular death. The generic name is empagliflozin and will be provided by Boehringer-Ingelheim. If the patient is randomized into the study drug group patients will receive empagliflozin 10 mg tablets once daily for a duration of 6 months.

Drug: Empagliflozin

Interventions

Empagliflozin DRUG

single oral tablet once daily.

Also known as: Jardiance

Empagliflozin

Placebo DRUG

single oral tablet once daily.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects ≥40 and ≤ 80 years of age
• History of type 2 diabetes
• Haemoglobin A1C ≥6.5 and ≤10 % within 3 months of the Screening Visit
• Established cardiovascular disease, defined as previous myocardial infarction ≥ 6 months ago, or previous coronary revascularization ≥ 2 months ago
• Any background antihyperglycemic therapy (which has been stable for at least 2 months)
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

You may not qualify if:

• Female subjects who are pregnant, lactating or of child bearing potential, or pre-menopausal women. (Menopause will be determined by patient and physician history)
• Type 1 diabetes
• Subjects currently treated with SGLT2 inhibitors, Glucagon-like peptide-1 (GLP1) receptor agonist, or saxagliptin
• Frequent episodes (\>4/month) of moderate hypoglycaemia, as defined by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
• Any episode of severe hypoglycaemia within the past 12 months, as also defined by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
• Subjects in whom coronary revascularisation by either Percutaneous coronary intervention (PCI) or bypass surgery is being contemplated within 6 months, or who have undergone revascularisation in the prior 2 months
• Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)\< 60 ml/min/1.73 m2 at screening
• Significant allergy or known intolerance to SGLT2 inhibitors or any ingredient in the formulations
• Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, haematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease and psychiatric disease
• Any malignancy not considered cured (except basal cell carcinoma of the skin). A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening
• Blood donation within 4 weeks prior to screening, or stated intention to donate blood or blood products during the period of the study or within one month following completion of the study
• Subjects who have participated in studies of an investigational drug or device within 30 days prior to the screening visit
• Conditions preventing safe MRI imaging such as the subject's weight exceeding 500 lbs; maximum body dimension from side-to-side exceeding 70 cm and from back to front of torso exceeding 50 cm or the presence of metallic fragments, clips or devices
• LVEF \<30% on the most recent assessment within 6 months
• New York Heart Association (NYHA) Class IV or recent hospitalization for decompensated Heart Failure (HF) (\<3 months)

Sponsors & Collaborators

• Unity Health Toronto: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (6)

• Pourafkari M, Connelly KA, Verma S, Mazer CD, Teoh H, Quan A, Goodman SG, Rai A, Ng MY, Deva DP, Triverio P, Jiminez-Juan L, Yan AT, Ge Y. Empagliflozin and left atrial function in patients with type 2 diabetes mellitus and coronary artery disease: insight from the EMPA-HEART CardioLink-6 randomized clinical trial. Cardiovasc Diabetol. 2024 Aug 28;23(1):319. doi: 10.1186/s12933-024-02344-6.

  PMID: 39198860 DERIVED

• Barbour W, Wolff E, Puar P, Hibino M, Bakbak E, Krishnaraj A, Verma R, Verma M, Quan A, Yan AT, Connelly KA, Teoh H, Mazer CD, Verma S. Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial. BMC Cardiovasc Disord. 2023 Nov 15;23(1):557. doi: 10.1186/s12872-023-03549-5.

  PMID: 37964221 DERIVED

• Puar P, Ahmed S, Hibino M, Pasricha A, Pandey A, Bari A, Verma R, Quan A, Yan AT, Connelly KA, Teoh H, Mazer CD, Verma S. The association between anthropometric indicators of obesity and cardiac reverse remodelling with empagliflozin in patients with type 2 diabetes and coronary artery disease. Diabetes Obes Metab. 2023 Sep;25(9):2765-2769. doi: 10.1111/dom.15119. Epub 2023 May 29. No abstract available.

  PMID: 37246798 DERIVED

• Sarak B, Verma S, David Mazer C, Teoh H, Quan A, Gilbert RE, Goodman SG, Bami K, Coelho-Filho OR, Ahooja V, Deva DP, Garg V, Gandhi S, Connelly KA, Yan AT. Impact of empagliflozin on right ventricular parameters and function among patients with type 2 diabetes. Cardiovasc Diabetol. 2021 Oct 4;20(1):200. doi: 10.1186/s12933-021-01390-8.

  PMID: 34607574 DERIVED

• Mason T, Coelho-Filho OR, Verma S, Chowdhury B, Zuo F, Quan A, Thorpe KE, Bonneau C, Teoh H, Gilbert RE, Leiter LA, Juni P, Zinman B, Jerosch-Herold M, Mazer CD, Yan AT, Connelly KA. Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease. JACC Cardiovasc Imaging. 2021 Jun;14(6):1164-1173. doi: 10.1016/j.jcmg.2020.10.017. Epub 2021 Jan 13.

  PMID: 33454272 DERIVED

• Verma S, Mazer CD, Yan AT, Mason T, Garg V, Teoh H, Zuo F, Quan A, Farkouh ME, Fitchett DH, Goodman SG, Goldenberg RM, Al-Omran M, Gilbert RE, Bhatt DL, Leiter LA, Juni P, Zinman B, Connelly KA. Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. Circulation. 2019 Nov 19;140(21):1693-1702. doi: 10.1161/CIRCULATIONAHA.119.042375. Epub 2019 Aug 22.

  PMID: 31434508 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Cardiovascular Diseases; Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 21, 2016
• Study Start: January 1, 2017
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: August 15, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)