Aortic StenosisPhase 2RELIEF-ASNCT07539259
Regression in Left Ventricular Hypertrophy and Fibrosis in Aortic Stenosis
A Phase 2 study testing Dapagliflozin (DAPA), Spironolactone (drug) and Spironolactone + Dapagliflozin in people with Aortic Stenosis, run by University College, London.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis
- What is being tested?
- Dapagliflozin (DAPA), Spironolactone (drug) and Spironolactone + Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 445 participants
- Where
- No sites listed yet
- Study dates
- Dec 2026to 28 Feb 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
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- 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.
- 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 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.
- 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).
- As evidenced by features of decompensated cirrhosis e.g. hepatic encephalopathy, ascites, jaundice or markedly deranged liver blood tests e.g. elevated bilirubin, serum albumin <30 or deranged clotting
About this study
Official title: 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.
Read more
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
- Being tested
- Dapagliflozin (DAPA), Spironolactone (drug), Spironolactone + Dapagliflozin, Epleronone
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin (DAPA)Drug
One tablet of Dapagliflozin once a day for the duration of the trial - 12 months (52 weeks).
Spironolactone (drug)Drug
One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
Spironolactone + DapagliflozinDrug
One tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
EplerononeDrug
If a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Active comparator | One tablet of Dapagliflozin once a day for the duration of the trial - 12 months Receives: Drug: Dapagliflozin (DAPA) |
| Spironolactone | Active comparator | One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks). Receives: 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). Receives: Drug: Spironolactone + Dapagliflozin; Drug: Epleronone |
| Standard of care | No intervention | Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2026
- Study startDec 2026 (estimated)
- Primary completionAug 2029 (estimated)
- Study completion28 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 445 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07539259
- Sponsor's protocol ID
- 181443
- Other IDs
- NIHR170907
- Acronym
- RELIEF-AS
- Status last verified
- Sep 2026
- First submitted
- 13 Apr 2026
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regression in Left Ventricular Hypertrophy and Fibrosis in Aortic Stenosis - a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT07539259
- Acronym / sponsor ID
- RELIEF-AS / 181443
- Conditions
- Aortic Stenosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 445 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Dec 2026 (estimated)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- 28 Feb 2030 (estimated)
- First posted
- 20 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Active comparator | Drug: Dapagliflozin (DAPA)One tablet of Dapagliflozin once a day for the duration of the trial - 12 months |
| Spironolactone | Active comparator | Drug: Spironolactone (drug), Drug: EplerononeOne tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks). |
| Dapagliflozin and Spironolactone | Active comparator | Drug: Spironolactone + Dapagliflozin, Drug: Eplerononeone tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks). |
| Standard of care | No intervention | –Standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin (DAPA)One tablet of Dapagliflozin once a day for the duration of the trial - 12 months (52 weeks). | Drug | Dapagliflozin |
| Spironolactone (drug)One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks). | Drug | Spironolactone |
| Spironolactone + DapagliflozinOne tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks). | Drug | Dapagliflozin and Spironolactone |
| EplerononeIf a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care. | Drug | Dapagliflozin and Spironolactone, Spironolactone |
Primary outcome
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/m^2.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
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Intravascular Lithotripsy in High Risk Calcified Iliac Anatomy for Transfemoral TAVR
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NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin (DAPA), Spironolactone (drug) and Spironolactone + Dapagliflozin in people with Aortic Stenosis, run by University College, London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the left ventricular mass indexed from pre Aortic Valve Replacement (AVR) to 12 months post AVR (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.