Aortic Stenosis
Conditions
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.
Interventions
One tablet of Dapagliflozin once a day for the duration of the trial - 12 months (52 weeks).
One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
One tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
DRUGEpleronone
If a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care.
Sponsors
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the left ventricular mass indexed from pre Aortic Valve Replacement (AVR) to 12 months post AVR | 12 months | Left ventricular mass indexed (LVMi) measured by cardiac MRI in g/m\^2. |
Outcome results
None listed