Regression in Left Ventricular Hypertrophy and Fibrosis in Aortic Stenosis - a Randomised Controlled Trial
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- University College, London
- Enrollment
- 445
- Primary Endpoint
- Change in the left ventricular mass indexed from pre Aortic Valve Replacement (AVR) to 12 months post AVR
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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.
Arms & Interventions
Dapagliflozin
One tablet of Dapagliflozin once a day for the duration of the trial - 12 months
Intervention: Dapagliflozin (DAPA) (Drug)
Standard of care
Standard of care
Spironolactone
One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
Intervention: Epleronone (Drug)
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).
Intervention: Epleronone (Drug)
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).
Intervention: Spironolactone + Dapagliflozin (Drug)
Spironolactone
One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
Intervention: Spironolactone (drug) (Drug)
Outcomes
Primary Outcomes
Change in the left ventricular mass indexed from pre Aortic Valve Replacement (AVR) to 12 months post AVR
Time Frame: 12 months
Left ventricular mass indexed (LVMi) measured by cardiac MRI in g/m2.
Secondary Outcomes
No secondary outcomes reported