The Role of SGLT2i in Management of Moderate AS

NCT06469645 | Recruiting Phase 2

• 1 other identifier: R212199
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

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.

Conditions

Moderate Aortic Valve Stenosis

Keywords

Aortic Valve Stenosis; Valvular Heart Disease; Myocardial Fibrosis; Empagliflozin; Echocardiography; Cardiac Magnetic Resonance Scan; Cardio-pulmonary Exercise Test; Sodium Glucose Cotransporter 2 Inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in indexed extracellular volume (iECV)

  The indexed extracellular volume (iECV) (expressed in ml/m2) will be assessed from the Cardiac Magnetic Resonance Scan at baseline and at 6 months follow-up

  6 months

Secondary Outcomes (7)

• Change in left ventricular ejection fraction

  6 months

• Change in left ventricular diastolic function as assessed by the E/A ratio

  6 months

• Change in indexed left ventricular mass

  6 months

• Change in percentage of myocardial uptake of late gadolinium enahncement (LGE)

  6 months

• Change in cardiac markers (N-terminal pro b-type natriuretic peptide and high sensitivity troponin)

  6 months

Study Arms (2)

Intervention Group

EXPERIMENTAL

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

Drug: Empagliflozin 10 MG

Control Group

NO INTERVENTION

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

Interventions

Empagliflozin 10 MG DRUG

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

Intervention Group

Eligibility Criteria

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

You may qualify if:

• Moderate aortic stenosis (aortic valve peak velocity ≥ 3m/s or mean gradient 20-40mmHg, or Aortic valve area 1.0-1.5cm2)
• Age over 18 years

You may not qualify if:

• 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.
• Previous valve replacement
• Severe hypertension (systolic \>180mmHg or diastolic \>100mmHg)
• Acute pulmonary oedema or cardiogenic shock
• Coexisting other valvular lesion of more than moderate severit.
• Coexisting hypertrophic cardiomyopathy or amyloidosis with cardiac involvement
• Any contraindications to MRI scanning including eGFR \<30ml/min/1.73m2
• Pregnancy or breast-feeding
• Concomitant SGLT2 inhibitor therapy
• Inability to receive SGLT2 inhibitor therapy
• History of diabetes type 1 or 2
• Severe peripheral vascular disease or non-healed leg ulcers
• Severe liver disease
• Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption

Sponsors & Collaborators

• University of East Anglia: lead
• Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK): collaborator

Study Sites (1)

Norfolk and Norwich University Hospital

Norwich, Norfolk, United Kingdom

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis; Heart Valve Diseases

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Vassilios S. Vassiliou, PhD

  University of East Anglia

  PRINCIPAL INVESTIGATOR

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: June 5, 2024
• First Posted: June 21, 2024
• Study Start: May 30, 2024
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: June 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)