Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects

NCT03485092 | Completed Phase 4

• 1 other identifier: GN15CA580
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesise that empagliflozin 10mg daily will have haemodynamic, cardiac, and renal benefits compared to placebo over 36 weeks in heart failure patients with type 2 diabetes (or pre-diabetes), leading to measurable improvements in clinical measures of cardiac structure and function (LVESVI, and LV strain) as well as renal blood flow.

Conditions

Heart Failure; Diabetes Mellitus

Keywords

heart failure; diabetes mellitus; empagliflozin; Randomised, placebo controlled trial

Outcome Measures

Primary Outcomes (2)

• Left Ventricular End Systolic Volume Index (LVESVI)

  Cardiac structure measured by left ventricular end-systolic volume index measured by cardiac magnetic resonance imaging as mL/m2

  36 weeks

• left ventricular global longitudinal strain (GLS)

  Cardiac structure measured by left ventricular global longitudinal strain measured by cardiac magnetic resonance imaging GLS%

  36 weeks

Secondary Outcomes (16)

• Left ventricular end diastolic volume index (LVEDVI)

  36 weeks

• Left ventricular ejection fraction (LVEF)

  36 weeks

• Left ventricular mass index (LVMI)

  36 weeks

• Left ventricular global function index (LVGFI)

  36 weeks

• Left atrial volume index (LAVI)

  36 weeks

Other Outcomes (10)

• Left ventricular global longitudinal strain (GLS)

  36 weeks

• Left ventricular global circumferential strain (GCS)

  36 weeks

• Left ventricular global radial strain (GRS)

  36 weeks

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Empagliflozin 10mg tablets for oral self-administration once daily

Drug: Empagliflozin 10 MG

Placebo Oral Tablet

PLACEBO COMPARATOR

placebo tablets for oral self-administration once daily

Drug: Placebo Oral Tablet

Interventions

Empagliflozin 10 MG DRUG

Empagliflozin 10mg tablets for oral self administration once a day

Empagliflozin

Placebo Oral Tablet DRUG

placebo tablets for oral self administration once a day

Placebo Oral Tablet

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Male or female, aged ≥18 years age
• Type 2 DM (diet-controlled or on stable treatment) or prediabetes
• Stable treatment defined as no change in oral therapy agents or doses for diabetes mellitus and (where applicable) \<10% change in average total daily insulin dose over last 6 weeks
• HbA1c ≤97 mmol/mol (11%) (routine available data from medical records, recorded in the last year)
• Prediabetes defined as HbA1c 39-47 mmol/mol (5.7-6.4%) at the time of screening (specifically for the prediabetes group, HbA1c will be repeated at the time of screening if there are no recent results within the last 3 months, in order to confirm the diagnosis of prediabetes)
• Heart failure (as defined by the presence of typical signs and symptoms of heart failure with documented reduced ejection fraction (ref SIGN and ESC guidelines))
• NYHA class II-IV
• LVEF ≤40%
• On stable doses of ACEI, ARB or ARNI for 4 weeks prior to randomisation unless contraindicated or not tolerated. They should also be taking a beta-blocker at a stable dose for 4 weeks unless contraindicated or not tolerated
• Women of childbearing potential (WOCBP) must be currently adhering to, or be willing to use, highly effective birth control methods for study treatment duration including:
• Combined hormonal contraception (oestrogen and progestogen containing medication) either orally, intravaginally, or transdermally
• Progesterone only hormonal contraception either orally, injected, or implanted
• Intrauterine device (IUD)
• Intrauterine hormone release system (IUS)

You may not qualify if:

• Type 1 DM
• History of hospital admission with a diagnosis of diabetic ketoacidosis (DKA)
• Insulin use within 1 year of diagnosis of diabetes
• History of acute or chronic pancreatitis
• eGFR \<30 ml/min/1.73m2 (derived using CKD EPI)
• Persistent/permanent atrial fibrillation/flutter (conditions which significantly impede MRI image interpretability)
• Acute coronary syndrome, stroke or surgery within 1 month (small type 2 MI in the context of acute HF does not apply)
• BMI \>52 kg/m2
• Liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal (ULN) during screening
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
• Any condition outside the cardiovascular and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator's clinical judgement
• Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma, adjuvant hormonal therapy for breast cancer and hormone therapy for prostate cancer)
• Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia)
• Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
• Any uncontrolled endocrine disorder except Type 2 DM

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator

Study Sites (1)

Queen Elizabeth University Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Related Publications (3)

• 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

• Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.

  PMID: 34693515 DERIVED

• Lee MMY, Brooksbank KJM, Wetherall K, Mangion K, Roditi G, Campbell RT, Berry C, Chong V, Coyle L, Docherty KF, Dreisbach JG, Labinjoh C, Lang NN, Lennie V, McConnachie A, Murphy CL, Petrie CJ, Petrie JR, Speirits IA, Sourbron S, Welsh P, Woodward R, Radjenovic A, Mark PB, McMurray JJV, Jhund PS, Petrie MC, Sattar N. Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF). Circulation. 2021 Feb 9;143(6):516-525. doi: 10.1161/CIRCULATIONAHA.120.052186. Epub 2020 Nov 13.

  PMID: 33186500 DERIVED

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

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

Study Officials

• Naveed Sattar, PhD

  Glasgow University and NHS GGC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, placebo controlled trial

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: April 2, 2018
• Study Start: March 16, 2018
• Primary Completion: March 28, 2020
• Study Completion: March 28, 2020
• Last Updated: September 18, 2020

Record last verified: 2020-09

Locations

GB (1)