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

University of Aarhus

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Left Ventricle Hypertrophied; Aortic Stenosis

Treatments: Drug: SGLT2 inhibitor; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05241431

DAPAS

Details and patient eligibility

About

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

Full 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.

Enrollment: 106 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed informed consent

2. Scheduled TAVR for significant symptomatic AS according to current guidelines

3. Age ≥ 18 years and < 85 years.

4. *

   • LVEF ≥ 40% and ≤ 50 % or LVEF ≥ 50% with at least one of the following:
   • LV GLS ≤ 15% by TTE
   • 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)

5. eGFR > 30 mL/min/1.73 m2

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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106 participants in 2 patient groups, including a placebo group

Intervention group

Active Comparator group

Description:

10 mg (oral) SGLT-2 inhibitor once daily

Treatment:

Drug: SGLT2 inhibitor

Control group

Placebo Comparator group

Description:

Placebo tablet encapsulated as the active treatment.

Treatment:

Drug: Placebo