A Randomised Controlled Trial 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 Than Standard-of-care Therapy Alone.

NCT07539259 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 181443NIHR170907
• Study Type: interventional
• Target: 445
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial aims to improve the heart health of people with a narrowed aortic valve called aortic stenosis (AS) who have their valve replaced through aortic valve replacement (AVR) by assessing the change in the mass of the left ventricle. In many patients even after an AVR, the heart still is 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 patients having an AVR recover better. It will assess two drugs, dapagliflozin and spironolactone, that have been shown to help patients with heart failure who do not have AS. We hope that 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.

Conditions

Aortic Stenosis

Outcome Measures

Primary Outcomes (1)

• 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/m2.

  12 months

Study Arms (4)

Dapagliflozin

ACTIVE COMPARATOR

One tablet of Dapagliflozin once a day for the duration of the trial - 12 months

Drug: Dapagliflozin (DAPA)

Spironolactone

ACTIVE COMPARATOR

One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).

Drug: Spironolactone (drug); Drug: Epleronone

Dapagliflozin and Spironolactone

ACTIVE COMPARATOR

one tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).

Drug: Spironolactone + Dapagliflozin; Drug: Epleronone

Standard of care

NO INTERVENTION

Standard of care

Interventions

Dapagliflozin (DAPA) DRUG

One tablet of Dapagliflozin once a day for the duration of the trial - 12 months (52 weeks).

Dapagliflozin

Spironolactone (drug) DRUG

One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).

Spironolactone

Spironolactone + Dapagliflozin DRUG

One tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).

Dapagliflozin and Spironolactone

Epleronone DRUG

If a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care.

Dapagliflozin and Spironolactone; Spironolactone

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• University College, London: lead

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

dapagliflozin; Spironolactone; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: April 20, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): February 28, 2030
• Last Updated: April 20, 2026

Record last verified: 2026-04