A Phase 2/3 interventional study of Empagliflozin 10 MG in Embolic Stroke of Undetermined Source and Atrial Fibrillation New Onset, sponsored by University of East Anglia. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-04.
Sponsored by University of East Anglia · Phase 2/3, Interventional, and Prevention
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.
Background:
Individuals who suffer an embolic stoke of undermined source represent 17% of all ischaemic stroke patients. When they undergo continuous cardiac rhythm monitoring with a loop recorder, a large portion of the population have been noted to develop atrial fibrillation (AF). In our own centre, 48.6% of patients have found to develop AF. This is considerably more than the proportion seen in patients undergoing ILR implantation for other reasons.
What remains unclear is whether this AF may have been responsible for the initial stroke, or is a reflection of an underlying atrial cardiopathy. Moreover, it is felt that this device detected AF is an important risk factor for stroke recurrence. Recent trials have suggested that whilst anticoagulation for device detected AF reduces future stroke, this is at the expense of a significant bleeding risk. Thus far, there have been no therapies that prevent the occurrence of AF, even in groups at high risk of AF development. Obviously such a strategy would negate the risk of bleeding associated with anticoagulation use. Such a strategy would reflect a paradigm shift in AF management.
Whilst studies have tried to explore the significance of abnormal atrial function in ESUS, generally crude assessments such as P-wave terminal force in V1 and brain natriuretic peptide had been utilised. Our group deep phenotyped over 300 ESUS patients. This work highlighted an important predictive role of left atrial strain for future device detected AF.
Left atrial strain has shown great promise as a marker of atrial dysfunction. There is growing evidence that sodium glucose 2 co-transporter inhibitors, such as empagliflozin, may prevent the development of AF. There have been over a dozen metaanalyses of the safety data from the large SGLT2i outcome trials, which have consistently shown that the SGLT2i arm was associated with lower incident AF compared to the control arm.
Similar results were seen in cohort studies including in Taiwan and the Food and Drug Association's adverse events reporting system. It is this finding that prompted the interest in utilising empagliflozin as the intervention in the trial.
Study aims and objectives:
The aims of this study are to assess if:
SGLT2 inhibitors can prevent adverse changes in left atrial function in patients who are felt to have an increased chance of AF development.
A nested MRI substudy will be used to try and provide mechanistic insight into how SGLT2 inhibitors may exert an antiarrhythmic effect.
Methods:
Given that the use of SGLT2 inhibitors to prevent atrial change has not been investigated before, we aim to investigate the hypotheses with an early stage randomised controlled trial.
For this, patients undergoing implantable loop recorder insertion for AF detection following an embolic stroke of undetermined source will be invited to participate. The participants will be randomised either to usual stroke care or to the intervention arm (use of SGLT2 inhibitor in addition to usual stroke care). They will be assessed at baseline and at 6-months following initiation of the medication. Both appointments will include echocardiography, electrocardiography and anthropometric assessments such as weight and grip strength.
From each arm, 10 patients will under also undergo advanced MRI imaging including MR spectroscopy, to try and investigate possible mechanisms for any effect of the SGLT2 inhibitor.
4,009 studies on the registry are indexed under Atrial Fibrillation; 961 are open to participants now.
This study's planned enrollment of 100 is below the median of 150 across 2,476 interventional studies indexed under Atrial Fibrillation.
Browse Atrial Fibrillation studies →University of East Anglia is the lead sponsor of 79 studies on the registry; 4 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patient has had an embolic stroke of undetermined source, defined as:
AND
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients randomised in this group will be taking the SLGT2 inhibitor (empagliflozin 10mg OD) in addition to usual stroke care
Drug: Empagliflozin 10 MG
Patients randomised in this group will continue to have their guideline directed stroke care
Participants allocated in the Intervention Group will be taking empagliflozin 10mg once a day in addition to their usual stroke care.
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
Time frame: 6 months
Difference in ILR-detected AF burden
AF will be detected via the implantable loop recorder
Time frame: 6 months
Difference in time to first AF episode
Time to first AF episode will be measured from time of ILR implantation to time of first AF detection
Time frame: 6 months
Change in P-wave terminal force
P-wave terminal force will be measured using the V1 lead on 12-lead ECG
Time frame: 6 months
Change in P-wave axis
P-wave axis will be measured using a 12-lead ECG
Time frame: 6 months
Change in LA volume
Indexed LA volume will be measured using apical 2 and apical 4 chamber views from transthoracic echocardiography
Time frame: 6 months
Plan to share: No
No publications or documents are linked to this record.
Started Nov 2024 (actual). Primary completion is estimated for Jul 2026, 20 months after the start.
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Studies of the drug tested here: Empagliflozin
University of East Anglia