Regression in Left Ventricular Hypertrophy and Fibrosis in Aortic Stenosis

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 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.

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/m\^2.

  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

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

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

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
• Left Ventricular Ejection Fraction (LVEF) ≥40%.
• Diagnosed with severe symptomatic aortic stenosis\* by a cardiologist or cardiac surgeon.
• o Severity of AS follows international guideline criteria \[38\], 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. \* including severe low flow low gradient AS
• 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
• Concomitant severe other valve lesion (severe MR, MS or AR)
• 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 or with a history of diabetic ketoacidosis
• Type 1 or Type 2 Diabetes on insulin.
• Concomitant diagnosis affecting trial participation or life expectancy of less than two years as evaluated by the treating clinician.
• Ongoing participation in another CTIMP interventional clinical trial (i.e. drug trial), will not be permitted. Participation in any other trial will need to be discussed with the trial investigators.

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: September 11, 2026

Record last verified: 2026-09