The Role of SGLT2i in Management of Moderate AS

NCT ID: NCT06469645

Last Updated: 2024-06-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-30
• Study Completion Date: 2026-02-28

Brief Summary

Background:

The aortic valve is like a door in the heart that lets blood flow out to the body. Over time, this valve can get worn out and become too narrow, leading to a condition called aortic stenosis. When this happens, the heart has to work extra hard to push blood through the narrow valve to supply the body with what it needs. This extra effort can cause the heart muscle to become abnormally thick or to have fibrosis. For people with aortic stenosis, this can lead to more problems like feeling out of breath, chest pain, and even needing to go to the hospital. It also increases the risk of dying from heart issues. There is a type of medication called Sodium Glucose Cotransporter 2 (SGLT2) inhibitors, which has been studied in people with weak heart muscle. These medicines were found to help the heart work better and improve the pumping of blood around the body. This can be promising for patients with aortic stenosis because it might make the heart muscle stronger and protect it from damage.

Aim of research study:

The aim of this study is to investigate whether the use of the drug empagliflozin, an SGLT2 inhibitor, prevents the formation of fibrosis or the abnormal thickening of the heart muscle in patients with aortic stenosis. Using advanced imaging techniques (such as echocardiography and cardiovascular magnetic resonance), we intend to study their effect on the heart muscle of patients with aortic stenosis.

Study design:

Patients with moderate aortic stenosis will be invited for participation. Eligible consenting patients will have a baseline assessment with cardiac MRI scan, echocardiography, cardiopulmonary exercise test and validated quality of life questionnaires. They will then be randomised to receive either the SGLT2i for 6 months, or standard of care. All patients will undergo the same tests at 6 months. This way, we aim to investigate the potential changes in the heart muscle and whether the SGLT2 inhibitor prevents fibrosis or hypertrophy.

Detailed Description

Background:

Aortic stenosis represents one of the commonest valvular heart diseases in the Western World. Studies have shown that as the valvular narrowing progresses, pathological left ventricular (LV) hypertrophy and fibrosis develop. This maladaptive left ventricular remodelling is associated with adverse events and worse long-term prognosis. Currently, there is no available medication to slow down or prevent these pathological processes occurring in aortic stenosis. Evidence from recent large randomised controlled trials have demonstrated that SGLT2 inhibitors have a significant positive impact on quality of life and cardiovascular outcomes of patients with heart failure. This is a result of complex mechanisms such as attenuation of cardiac myofibroblast activity and collagen remodelling. These could be proved to be very beneficial for patients with aortic stenosis since the left ventricular pathological changes occurring in aortic stenosis share similar pathways and mechanisms with heart failure.

Study aims and objectives:

The aims of this study are to assess if:

• SGLT2 inhibitors can prevent or decelerate adverse myocardial remodelling and fibrosis.
• SGLT2 inhibitors can improve the exercise tolerance and functional capacity of patients with aortic stenosis.

Methods:

Given that the use of SGLT2 inhibitors in aortic stenosis has not been investigated before, we aim to investigate the hypotheses with an early stage randomised controlled trial. For this, patients with moderate aortic stenosis identified in the outpatient cardiology clinic will be invited to participate. Management of moderate aortic stenosis is conservative with a 'watchful waiting' approach. The participants will be randomised either to usual conservative management or to the intervention group (use of SGLT2 inhibitor on top of regular medications). They will be assessed at baseline and at 6-months following initiation of the medication. Both appointments will include evaluation of symptoms (with the use of validated questionnaire) and functional capacity (cardiopulmonary exercise test), electrocardiogram and blood tests. An echocardiogram, a scan performed routinely on a yearly basis for all patients with moderate aortic stenosis, will also be performed at baseline and at completion of the 6 months' follow-up period to evaluate for myocardial hypertrophy and remodelling. Additionally, a cardiopulmonary exercise test and a cardiac magnetic resonance scan will be performed in these two timepoints to assess for myocardial remodelling and fibrosis.

Conditions

Moderate Aortic Valve Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Intervention Group

Patients randomised in this group will be taking the SLGT2 inhibitor (empagliflozin) on top of their regular medications for 6 months.

Group Type: EXPERIMENTAL

Empagliflozin 10 MG

Intervention Type: DRUG

Participants allocated in the Intervention Group will be taking empagliflozin 10mg once a day on top of their regular medications.

Control Group

Patients randomised in this group will continue to have their guideline directed conservative management with no changes in their regular medications.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Empagliflozin 10 MG

Participants allocated in the Intervention Group will be taking empagliflozin 10mg once a day on top of their regular medications.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Moderate aortic stenosis (aortic valve peak velocity ≥ 3m/s or mean gradient 20-40mmHg, or Aortic valve area 1.0-1.5cm2)

2. Age over 18 years

Exclusion Criteria

1. Severe aortic stenosis (aortic valve peak velocity ≥ 4m/s or mean > 40mmHg or Aortic valve area < 1.0cm2) or planned cardiac surgery or likely need for surgery within 6 months.

2. Previous valve replacement

3. Severe hypertension (systolic >180mmHg or diastolic >100mmHg)

4. Acute pulmonary oedema or cardiogenic shock

5. Coexisting other valvular lesion of more than moderate severit.

6. Coexisting hypertrophic cardiomyopathy or amyloidosis with cardiac involvement

7. Any contraindications to MRI scanning including eGFR <30ml/min/1.73m2

8. Pregnancy or breast-feeding

9. Concomitant SGLT2 inhibitor therapy

10. Inability to receive SGLT2 inhibitor therapy

11. History of diabetes type 1 or 2

12. Severe peripheral vascular disease or non-healed leg ulcers

13. Severe liver disease

14. Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)

OTHER

Sponsor Role: collaborator

University of East Anglia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vassilios S. Vassiliou, PhD

Role: PRINCIPAL_INVESTIGATOR

University of East Anglia

Locations

Norfolk and Norwich University Hospital

Norwich, Norfolk, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Vassilios S. Vassiliou, PhD

Role: CONTACT

v.vassiliou@uea.ac.uk

01603592534

Facility Contacts

Vassilios S. Vassiliou, PhD

Role: primary

v.vassiliou@uea.ac.uk

0160592534

Other Identifiers

R212199

Identifier Type: -

Identifier Source: org_study_id