EMPA-ESUS. a Randomised Control Trial to Investigate the Impact of Empagliflozin on Left Atrial Function in Patients with Embolic Stroke of Undetermined Source

NCT06715449 | Recruiting Phase 2

• 1 other identifier: IRAS: 318615
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) is the most common heart rhythm problem in the adult population. There is a five-fold increase in stroke risk in patients with AF. Whilst there has been considerable advances in AF management including improvement in ablation therapy, preventing AF remains an unmet need. One promising avenue is a group of medications called Sodium Glucose Cotransporter 2 (SGLT2) inhibitors, which has been studied in people with diabetes, kidney disease and weak heart muscle. These medicines were consistently found to lower the risk of developing AF. This can be promising for patients who have suffered a stroke for unclear reasons, where a significant proportion are subsequently found to have short periods of AF. Often prior to AF development, patients may have changes in the structure or function of the top chambers of their heart (the atria). This may provide a useful marker for us to understand whether SGLT2i impacts AF risk. Aim of research study: The aim of this study is to investigate whether the use of the drug empagliflozin, an SGLT2 inhibitor, prevents changes in the left atrium associated with future AF development. Using advanced imaging techniques and continuous rhyth monitoring we intend to study the effect of SGLT2 inhibitors on left atrial function and arrhythmia occurence. Study design: Patients who are undergoing an implantable loop recorder insertion, to detect AF following a stroke, will be invited for participation. Eligible consenting patients will have a baseline assessment with echocardiography, electrocardiogram and anthropometric measures. They will then be randomised to receive either the SGLT2i alongside usual stroke care for 6 months, or usual stroke care alone. All patients will be monitored remotely via their loop recorder, and will undergo repeat electrocardiogpahic, echocardiographic and anthropometric assessment at 6 months. This way, we aim to investigate whether the SGLT2 inhibitor causes changes in atrial parameters that may be associated with future AF development.

Conditions

Embolic Stroke of Undetermined Source; Atrial Fibrillation New Onset

Keywords

Atrial strain

Outcome Measures

Primary Outcomes (1)

• Change in left atrial reservoir strain

  The left atrial reservoir strain (LArs) (expressed in %) will be assessed from the echocardiogram at baseline and at 6 months follow-up

  6 months

Secondary Outcomes (5)

• Difference in ILR-detected AF burden

  6 months

• Difference in time to first AF episode

  6 months

• Change in P-wave terminal force

  6 months

• Change in P-wave axis

  6 months

• Change in LA volume

  6 months

Study Arms (2)

Intervention group: Empagliflozin + usual stroke care

EXPERIMENTAL

Patients randomised in this group will be taking the SLGT2 inhibitor (empagliflozin 10mg OD) in addition to usual stroke care

Drug: Empagliflozin 10 MG

Control group: Usual stroke care alone

NO INTERVENTION

Patients randomised in this group will continue to have their guideline directed stroke care

Interventions

Empagliflozin 10 MG DRUG

Participants allocated in the Intervention Group will be taking empagliflozin 10mg once a day in addition to their usual stroke care.

Intervention group: Empagliflozin + usual stroke care

Eligibility Criteria

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

You may qualify if:

• Age over 18 years
• Patient has had an embolic stroke of undetermined source, defined as:
• Ischaemic stroke or transient ischaemic attack diagnosed clinically + supporting radiological features on CT or MRI imaging
• No clinically significant extracranial or intracranial atherosclerosis found on neck imaging
• No evidence of prevalent cardioembolic source of embolism - atrial dysrhythmia, cardiac thrombus, prosthetic valve, cardiac tumours, mitral stenosis, recent MI, LVEF\<35%, valvular vegetations, or infective endocarditis
• AND
• No other specific stroke aetiology identified (pro-thrombotic states, arteritis, dissection, drug abuse)
• Patient has been referred for an implantable loop recorder implant to investigate possible atrial dysrhythmia
• Ability to give written, informed consent

You may not qualify if:

• Prevalent atrial fibrillation or atrial flutter
• Subsequent demonstration of a cardio-emoblic source
• Pre-existent indication for SGLT2i including heart failure with a reduced ejection fraction and Type 1 or Type 2 diabetes mellitus
• Contraindication to the commencement of SGLT2i including a history of, or risk factors for diabetic ketoacidosis, such as restricted food intake or a history of alcohol abuse
• Hypersensitivity to the active substance or to any of the excipients of empagliflozin
• Presence of alternate implantable cardiac devices such as a pacemaker or defibrillator, that would make ILR utilisation redundant
• Any condition that may confound the results or interfere with participation such as dementia
• An unwillingness to participate

Sponsors & Collaborators

• University of East Anglia: lead
• Addenbrookes Hospital, Cambridge: collaborator

Study Sites (1)

Addenbrookes Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

MeSH Terms

Interventions

empagliflozin

Central Study Contacts

Vassilios S Vassiliou, PhD

CONTACT

01603592534; V.Vassiliou@uea.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel-group prospective randomised open-label blinded endpoint (PROBE) controlled trial

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 4, 2024
• Study Start: November 22, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)