Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000355875
Ethics application status
Approved
Date submitted
23/02/2021
Date registered
30/03/2021
Date last updated
2/03/2022
Date data sharing statement initially provided
30/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised trial of Empagliflozin and Left ventricular diastolic function in Acute Coronary Syndrome and Type 2 Diabetes (RELACS-T2D)
Scientific title
Randomised trial of Empagliflozin and Left ventricular diastolic function in adults with Acute Coronary Syndrome and Type 2 Diabetes (RELACS-T2D)
Secondary ID [1] 303536 0
None
Universal Trial Number (UTN)
Trial acronym
RELACS-T2D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes mellitus 320870 0
Acute coronary syndrome 320871 0
Condition category
Condition code
Cardiovascular 318691 318691 0 0
Coronary heart disease
Metabolic and Endocrine 319027 319027 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following an acute coronary syndrome (ACS), participants with diabetes will be randomised 1:1 to one of the following two groups:
1) Empagliflozin (Jardiance®) 10 mg daily (open-label) orally for 6 months.
2) No sodium-glucose co-transporter 2 (SGLT2) inhibitor treatment (control).

The design allows clinicians to consider other glucose-lowering therapies as part of usual care if glycaemic control is suboptimal. Empagliflozin, a commonly used medication, is approved by the Therapeutic Goods Administration (TGA) and is Pharmaceutical Benefits Scheme (PBS) subsidised for patients with type 2 diabetes and HbA1c >7% despite treatment with either metformin or a sulfonylurea. Adherence to medications will be monitored at the follow-up and may involve checking with the participant's pharmacy for dispensing record. At the 6-month follow-up visit, participants not randomised to empagliflozin will be commenced on a SGLT2 inhibitor if eligible based on PBS criteria as part of usual care.
Intervention code [1] 319820 0
Treatment: Drugs
Comparator / control treatment
Following an ACS, participants with diabetes will be randomised 1:1 to one of the following two groups:
1) Empagliflozin (Jardiance®) 10 mg daily (open-label).
2) No sodium-glucose co-transporter 2 (SGLT2) inhibitor treatment (control) - these participants will be treated using other glucose-lowering medications.
Control group
Active

Outcomes
Primary outcome [1] 326632 0
Left ventricular diastolic function (mitral valve peak E-wave and A-wave velocities, mitral valve early diastolic deceleration time, septal and lateral annular early diastolic (e’) velocities, left atrial volume and diastolic functional reserve) as measured by echocardiography
Timepoint [1] 326632 0
Baseline and 6 months
Primary outcome [2] 326932 0
Left ventricular mass indexed to body surface area as measured by echocardiography
Timepoint [2] 326932 0
Baseline and 6 months
Secondary outcome [1] 392213 0
Left ventricular systolic function (ejection fraction and global longitudinal strain) as measured by echocardiography
Timepoint [1] 392213 0
Baseline and 6 months
Secondary outcome [2] 393171 0
Exercise time and metabolic equivalents (METs) as measured by stress testing
Timepoint [2] 393171 0
Baseline and 6 months
Secondary outcome [3] 393172 0
Biomarkers (N-terminal pro B-type natriuretic peptide, glycated haemoglobin, inflammation) as measured by plasma analysis
Timepoint [3] 393172 0
Baseline and 6 months

Eligibility
Key inclusion criteria
• Type 2 diabetes already on metformin and/or sulfonylurea therapy unless contraindicated.
• Admission to hospital for ACS, defined as ST-segment myocardial infarction, non-ST-segment elevation myocardial infarction or unstable angina, and undergoing coronary.
Minimum age
20 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of diabetic ketoacidosis.
• Baseline HbA1c <7% or >10%.
• Current SGLT2 inhibitor or glucagon-like peptide-1 agonist use or prior use within the last 6 months.
• Atrial fibrillation or other serious cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation or complete heart block).
• Moderate or severe valvular heart disease or previous valve surgery.
• Renal impairment with an estimated glomerular filtration rate of <45 ml/min/1.73m2.
• Hospital re-admission for a cardiac-related event during the trial, such as myocardial infarction, arrhythmia, heart failure, myocarditis, endocarditis, pericarditis or cardiac procedure/surgery.
• Unstable ACS.
• Active foot ulcer or gangrene.
• Planned coronary intervention or bypass grafting during time of follow-up.
• Unable to perform supine bicycle stress echocardiography.
• Hypertension (systolic blood pressure >200 and/or diastolic blood pressure >110 mmHg).
• Inability to provide informed consent.
• Pregnant or breastfeeding women.
• Known hypersensitivity to empagliflozin.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/04/2021
Actual
13/10/2021
Date of last participant enrolment
Anticipated
31/03/2022
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
80
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 307959 0
Charities/Societies/Foundations
Name [1] 307959 0
Diabetes Research WA
Country [1] 307959 0
Australia
Primary sponsor type
Hospital
Name
Fiona Stanley Hospital
Address
11 Robin Warren Dr, Murdoch WA 6150
Country
Australia
Secondary sponsor category [1] 308675 0
None
Name [1] 308675 0
None
Address [1] 308675 0
None
Country [1] 308675 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307954 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 307954 0
South Metropolitan Health Service Executive
Level 2, Education Building, Fiona Stanley Hospital
14 Barry Marshall Parade
MURDOCH Western Australia 6150
Ethics committee country [1] 307954 0
Australia
Date submitted for ethics approval [1] 307954 0
09/01/2021
Approval date [1] 307954 0
26/03/2021
Ethics approval number [1] 307954 0

Summary
Brief summary
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce heart failure hospitalisation in patients with type 2 diabetes (T2D) at high cardiovascular risk and in patients with heart failure (HF) with reduced ejection fraction without or without diabetes. However, the mechanisms by which SGLT2 inhibitors reduce the risk of HF remains unclear. Previous studies have demonstrated that SGLT2 inhibitors can reduce left ventricular (LV) mass and improve LV diastolic function in stable outpatients with T2D and in patients with HF with reduced ejection fraction. We recently performed the first study to assess the effects of empagliflozin (an SGLT2 inhibitor) on LV function following an acute coronary syndrome (ACS) in patients with T2D. The observational study found that empagliflozin reduces LV mass and improves LV diastolic function in this cohort, which means that empagliflozin could potentially improve the heart’s pumping function after a heart attack or an angina episode. This had led to the design of the Randomised trial of Empagliflozin and Left Ventricular diastolic function in Acute Coronary Syndrome and Type 2 Diabetes (RELACS-T2D).

Following an ACS, 80 participants with T2D at Fiona Stanley Hospital (FSH) will be randomised 1:1 in this open-label trial to either 1) Empagliflozin or 2) no SGLT2 inhibitor therapy. Diastolic stress echocardiography (DSE) using supine bicycle will be performed at baseline and at 6 months follow-up. Echocardiography will be performed by certified sonographers and reported by a consultant Cardiologist who are both blinded to treatment allocation. Results at follow-up will be compared to baseline by a blinded investigator to assess for significant changes in LV function between groups. Non-fasting blood samples will be collected at baseline and follow-up and analysed to detect significant associations. We hypothesise that empagliflozin treatment can reduce adverse LV remodelling and improve LV diastolic function following an ACS in patients with T2D.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109026 0
Prof Girish Dwivedi
Address 109026 0
Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150
Country 109026 0
Australia
Phone 109026 0
+61 861524130
Fax 109026 0
Email 109026 0
[email protected]
Contact person for public queries
Name 109027 0
Nick Si Rui Lan
Address 109027 0
Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150
Country 109027 0
Australia
Phone 109027 0
+61 861522222
Fax 109027 0
Email 109027 0
[email protected]
Contact person for scientific queries
Name 109028 0
Nick Si Rui Lan
Address 109028 0
Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150
Country 109028 0
Australia
Phone 109028 0
+61 861522222
Fax 109028 0
Email 109028 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.