ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

RELACS-T2D

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Diabetes mellitus

Acute coronary syndrome

Condition category

Condition code

Cardiovascular

Coronary heart disease

Metabolic and Endocrine

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]

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]

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]

Baseline and 6 months

Primary outcome [2]

Left ventricular mass indexed to body surface area as measured by echocardiography

Timepoint [2]

Baseline and 6 months

Secondary outcome [1]

Left ventricular systolic function (ejection fraction and global longitudinal strain) as measured by echocardiography

Timepoint [1]

Baseline and 6 months

Secondary outcome [2]

Exercise time and metabolic equivalents (METs) as measured by stress testing

Timepoint [2]

Baseline and 6 months

Secondary outcome [3]

Biomarkers (N-terminal pro B-type natriuretic peptide, glycated haemoglobin, inflammation) as measured by plasma analysis

Timepoint [3]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Diabetes Research WA

Address [1]

Ainslie House, 48 Murray St, Perth WA 6000

Country [1]

Australia

Primary sponsor type

Hospital

Name

Fiona Stanley Hospital

Address

11 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South Metropolitan Health Service Human Research Ethics Committee

Ethics committee address [1]

South Metropolitan Health Service Executive
Level 2, Education Building, Fiona Stanley Hospital
14 Barry Marshall Parade
MURDOCH Western Australia 6150

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/01/2021

Approval date [1]

26/03/2021

Ethics approval number [1]

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

Prof Girish Dwivedi

Address

Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Phone

+61 861524130

Fax

girish.dwivedi@perkins.uwa.edu.au

Contact person for public queries

Name

Nick Si Rui Lan

Address

Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Phone

+61 861522222

Fax

nick.lan@health.wa.gov.au

Contact person for scientific queries

Name

Nick Si Rui Lan

Address

Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Phone

+61 861522222

Fax

nick.lan@health.wa.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.

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