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Aortic StenosisPhase 2/3DAPASNCT05241431

Effect of Dapagliflozin on Myocardial and Renal Function Following Aortic Valve Stenosis Intervention

A Phase 2/3 study testing SGLT2 inhibitor in people with Aortic Stenosis and Left Ventricle Hypertrophied, run by University of Aarhus at 1 site in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Randomized, double-blinded, placebo-controlled study in AS patients with subclinical or clinical heart failure undergoing treatment with TAVR. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Aortic Stenosis, Left Ventricle Hypertrophied
What is being tested?
SGLT2 inhibitor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
106 participants
Where
1 siteDenmark
Study dates
12 Feb 2022to 1 Apr 2024
Phase
Phase 2/3
Are there results?
None posted in the registry

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 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent
  • Scheduled TAVR for significant symptomatic AS according to current guidelines
  • Age ≥ 18 years and < 85 years.
  • *
  • LVEF ≥ 40% and ≤ 50 % or LVEF ≥ 50% with at least one of the following:
  • LV GLS ≤ 15% by TTE
Show all 9Show fewer
  • LV septum or posterior wall thickness ≥ 12mm by TTE or LV mass index ≥108/131 g/m2 for females/males (mild LVH)
  • LVEF ≥ 50 % and Nt-proBNP > 600/900 ng/l (sinus rhythm/atrial fibrillation)
  • eGFR > 30 mL/min/1.73 m2

Who cannot join

  • Medically treated type 1 or type 2 diabetes mellitus
  • Ongoing treatment with an SGLT2-inhibitor or intolerance to SGLT2-inhibitors
  • Life expectancy < 12 months
  • Symptomatic hypotension or persistent SBP < 100 mmHg
  • Contraindications to CMRI
  • HF due to restrictive or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis or hypertrophic obstructive cardiomyopathy
Show all 12Show fewer
  • Additional other untreated severe valvular disease
  • Liver failure
  • Women who are pregnant or plan to be within the study period.
  • Allergy to any substance in the project medicine, both placebo and active medicine.
  • Previous renal transplantation.
  • Chronic dialysis treatment.

Trial locations and contacts

1 site in 1 country.

Anders Lehmann Dahl Pedersen, MD contact

0045 2785 2009

anlepe@rm.dk

Denmark1 site, 1 recruiting

  • Aarhus University Hospital

    Aarhus, 8200

    Anders Lehmann Dahl Pedersen, MD

    Recruiting

Other trials in Denmark

About this study

Randomized, double-blinded, placebo-controlled study in AS patients with subclinical or clinical heart failure undergoing treatment with TAVR.

Read the detailed description

This is a randomized, double-blinded, placebo-controlled study in AS patients with subclinical or clinical heart failure undergoing treatment with TAVR. It evaluates the effect of Dapagliflozin versus placebo, given once daily in addition to background standard medical therapy. Patients who are scheduled for TAVR at Aarhus University Hospital (AUH) will be informed about the project and invited to participate if they fulfill the inclusion criteria prior to the TAVR procedure.

Patients will be randomized 1:1 in blocks of 6 patients to either Dapagliflozin 10 mg daily or placebo within 1 months prior to the scheduled TAVR therapy.

The total treatment period is 13 months with 6 scheduled outpatient clinic visits at baseline (before TAVR) and at 1, 3, 6, 9, 12 months after TAVR.

Cardiac magnetic resonance imaging (CMRI) is performed at baseline and 12 months follow-up. Echocardiography is performed at baseline, 1- and 12 months. 24-hour ambulatory blood pressure is measured at baseline and 12-months post-TAVR. Clinical status, HF questionnaire and blood samples will be performed at each visit. Drug accountability and adherence to the protocol is evaluated at each visit.

A sub study in 40 of the included patients (20 treated with Dapagliflozin and 20 placebo) is planned. This will include additional endomyocardial biopsies taken at baseline and 12-months follow-up for high resolution respirometry (mitochondrial function) and electron microscopy (mitochondrial structure and interstitial fibrosis) supplemented by right heart catherization (RHC) for hemodynamic assessment.

Being tested
SGLT2 inhibitor, Placebo
Medical subject headings
Aortic Valve Stenosis, Hypertrophy, Left Ventricular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SGLT2 inhibitorDrug

    10 mg orally once daily in addition to standard medical treatment.

  • PlaceboDrug

    Placebo tablets similar to active treatment.

Study groups in NCT05241431
Study groupRoleWhat they receive
Intervention groupActive comparator10 mg (oral) SGLT-2 inhibitor once daily
Receives: Drug: SGLT2 inhibitor
Control groupPlacebo comparatorPlacebo tablet encapsulated as the active treatment.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite endpoint of changes in LV mass, systolic function, eGFR, and serum Nt-proBNP

    Changes from baseline to 12 months of follow-up in at least 2 out of 4 well-known parameters is required to reach the primary endpoint:

    • LVMi (grams) reduction of 10 % point (by CMRI)
    • LV GLS (percent) absolute increase of 2.0 % point (by TTE)
    • A decrease in serum Nt-proBNP (ng/L) of more than 25%
    • Relative increase of 10% in eGFR (ml/min/1.73m^2) If 2 or more of the 4 outcome measures are reached at 12-months follow-up, the patient has fulfilled the primary end-point.

    Measured: Baseline assesment to 12-months follow-up post-TAVR

Secondary outcomes (17)

  1. Difference in the change in eGFR

    Difference between active treatment and placebo at 12-months follow-up

    Measured: baseline to 12-months

  2. Difference in eGFR

    Difference between active treatment and placebo at 12-months follow-up

    Measured: 12-months

  3. The number of patients with a relative difference of 10 % of myocardial interstitial fibrosis evaluated by the biomarker extracellular volume (ECV) by late enhancement gadolinium by CMR

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months

  4. The number of patients with a >10% decrease in cardiac fibrosis when assessed by histology and quantified by stereology (sub study)

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months

  5. The number of patients with an increase in the respiratory control ratio (RCR) by ≥10% measured by High Resolution Respirometry (HRR) (sub study)

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months

  6. Composite endpoint of worsening HF with hospitalization or urgent outpatient clinical visit due to HF, and all-cause mortality.

    Difference between active treatment and placebo in the incidence rate of hospitalization due to worsening heart failure or urgent clinical visit due to heart failure and all-cause mortality (using dates of the events to assess the incidence rates in the two groups: active treatment and placebo.

    Measured: 12-months post-TAVR

  7. All-cause mortality

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months post-TAVR

  8. Worsening HF with hospitalization or urgent outpatient clinical visit due to HF

    Difference between active treatment and placebo.

    Measured: 12-months post-TAVR

  9. Difference in the change in urinary albumin/creatinine ratio

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months

  10. Difference in ACR at 12-months follow-up

    Difference between active treatment and placebo.

    Measured: 12-months follow-up

  11. 24-hour ambulatory blood pressure changes

    Difference between active treatment and placebo in both systolic and diastolic blood pressure.

    Measured: baseline to 12 months

  12. Change from baseline to 12-months follow-up in the Kansas City Cardiomyopathy questionnaire

    Change from baseline in KCCQ will be reported. The KCCQ is a 23-item, self-administered questionnaire with score range of 0 to 100, and higher scores indicating better health. Difference in score for active treatment vs. placebo.

    Measured: Baseline to 12-months

  13. Change from baseline to 12-months follow-up in New York Heart Association-class (NYHA)

    The NYHA functional classification categorizes the extent of heart failure by placing subjects in one of four (I, II, III, IV) categories based on how much they are limited during physical activity and symptoms of shortness of breath and/or angina. Shift in NYHA-class between active treatment group and placebo.

    Measured: baseline to 12-months.

  14. LVMi reduction of 10 % point (by CMRI)

    Difference between active treatment and placebo.

    Measured: baseline to 12-months.

  15. LV GLS absolute increase of 2.0 % point (by TTE)

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months follow-up

  16. A decrease in serum Nt-proBNP of more than 25% follow-up

    Difference between active treatment and placebo.

    Measured: baseline to 12-months follow-up.

  17. Relative increase of 10% in eGFR

    Difference between active treatment and placebo.

    Measured: Baseline to 12-months follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2022
  2. Study start12 Feb 2022
  3. Primary completion1 Mar 2024 (estimated)
  4. Study completion1 Apr 2024 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
106 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05241431
Sponsor's protocol ID
DAPAS
Acronym
DAPAS
Status last verified
Jan 2022
First submitted
18 Jan 2022
Last updated
15 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing SGLT2 inhibitor in people with Aortic Stenosis and Left Ventricle Hypertrophied, run by University of Aarhus at 1 site in Denmark.

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 9 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 15 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Anders Lehmann Dahl Pedersen, MD (0045 2785 2009, anlepe@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite endpoint of changes in LV mass, systolic function, eGFR, and serum Nt-proBNP (time frame: Baseline assesment to 12-months follow-up post-TAVR). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05241431.

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 15 Feb 2022.

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