To Establish Whether Dapagliflozin and Spironolactone in Patients With Severe Aortic Stenosis Undergoing Aortic Valve Replacement, Result in Better Left Ventricular Mass Regression, Myocardial Health and Patient Reported Outcomes (RELIEF-AS)

Regression in Left Ventricular Hypertrophy and Fibrosis in Aortic Stenosis - a Randomised Controlled Trial

This trial aims to improve the heart health of people with a narrowed aortic valve called aortic stenosis (AS) who then have aortic valve replacement (AVR) by assessing the change in the mass of the left ventricle.

Even after an AVR in many patients the heart is still unable to pump as well and can lead to heart failure.

This study will assess if medication used in other causes of heart failure can help participants having an AVR recover better. Researchers will compare two drugs, dapagliflozin and spironolactone, that have been shown to help patients with heart failure who do not have AS, to see if taking one or both medicines together will help patients with AS.

There will be four treatment arms: dapagliflozin, spironolactone, dapagliflozin and spironolactone together, and standard of care. These will be taken as one tablet of each IMP per day for 12 months.

Participants will have approximately four follow up visits, dependent on the treatment arm - those in an arm with spironolactone will have an extra safety follow up visit.

These medicines might help patients after AVR by reducing heart muscle thickness and scarring.

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Stenosis
• Intervention / Treatment: Drug: Dapagliflozin (DAPA); Drug: Spironolactone (drug); Drug: Epleronone; Drug: Spironolactone + Dapagliflozin

• Study Type: Interventional
• Enrollment (Estimated): 445
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants ≥ 18 years
• LVEF ≥40%.

• Diagnosed with severe symptomatic AS by the clinical care team.

  o Severe AS defined according to international guideline criteria, namely at least one out of: effective orifice area [EOA] <1.0 cm2, indexed EOA of 0.6 cm2/m2, peak velocity >4.0 m/s or mean gradient >40 mmHg.

• Referred for surgical or transcatheter AVR (SAVR or TAVI).
• Able to provide informed consent and comply with study procedures.

Exclusion Criteria:

• Current use or intolerance or hypersensitivity to MRAs or SGLT2-inhibitors.
• Hyperkalaemia (K>4.5 mmol/L)
• Significant renal impairment (eGFR < 45 mL/min/1.73m²)
• Severe hepatic insufficiency

• Contraindications to MRAs including:

  • Addison's disease.
  • Acute porphyrias.
  • Receiving potassium-sparing diuretics, potassium supplements or strong inhibitors of CYP 3A4 (for example. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone).

• Contraindications to SGLT2-inhibitors including:

  • Active urinary tract infections.
  • At risk of diabetic ketoacidosis (e.g. Type 1 diabetes mellitus)
• Concomitant diagnosis affecting trial participation or life expectancy of less than two years.
• History of significant arrhythmias or other cardiac conditions that would interfere with the trial outcomes.
• Contraindications to MRI (e.g. non-conditional cardiac pacemaker, severe claustrophobia, inability to lie flat: participants who do not meet local safety rules for MRI). NB: Conditional pacemakers/ICDs, if implanted after the baseline scan, are not an exclusion, depending on local expertise.
• Ongoing participation in another interventional clinical trial.
• Significant comorbidities that would contraindicate participation, including uncontrolled hypertension, or recent myocardial infarction (within 3 months prior to screening).
• Pregnancy or breastfeeding, or females of childbearing potential not using an effective method of contraception.
• Any other medical or psychiatric condition that would interfere with participation or compliance with study procedures as determined by the Principal Investigator (PI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care
Active Comparator: Dapagliflozin; One tablet of Dapagliflozin once a day for the duration of the trial - 12 months	Drug: Dapagliflozin (DAPA); One tablet of Dapagliflozin once a day for the duration of the trial - 12 months (52 weeks).
Active Comparator: Spironolactone; One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).	Drug: Spironolactone (drug); One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).; Drug: Epleronone; If a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care.
Active Comparator: Dapagliflozin and Spironolactone; one tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).	Drug: Epleronone; If a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care.; Drug: Spironolactone + Dapagliflozin; One tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the left ventricular mass indexed from pre Aortic Valve Replacement (AVR) to 12 months post AVR	Left ventricular mass indexed (LVMi) measured by cardiac MRI in g/m^2.	12 months

Collaborators and Investigators

• Sponsor: University College, London

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Organic Chemicals; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Lactones; Pregnenes; Spironolactone; dapagliflozin; Pharmaceutical Preparations
• Other Study ID Numbers: 181443; NIHR170907 (Other Grant/Funding Number: NIHR EME Programme)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No