The effect of treatment with Dapagliflozin on heart and kidney function after catheter based aortic valve replacement for aortic stenosis

Effect of Dapagliflozin on myocardial and renal function following aortic valve stenosis intervention - DAPAS

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-004271-14-DK

Enrollment

104

Registered

2021-10-20

Start date

2021-12-06

Completion date

Unknown

Last updated

2024-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients with aortic stenosis undergoing trans catheter aortic valve replacement. MedDRA version: 20.0 Level: LLT Classification code 10058186 Term: Aortic valve stenosis and insufficiency System Organ Class: 100000004849

Interventions

Product Name: Forxiga Pharmaceutical Form: Tablet INN or Proposed INN: Dapagliflozin CAS Number: 461432-26-8 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10- Pha

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Signed informed consent 2. Scheduled TAVR for significant symptomatic AS according to current guidelines 3. Age > 18 years and /= 40% and 50% with LV GLS /= 12mm by echo 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90

Exclusion criteria

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.

Design outcomes

Primary

Measure	Time frame
Main Objective: The overall purpose of this study is to improve treatment of AS patients treated with TAVR. The study evaluates the effect of Dapagliflozin on mitochondrial function, myocardial fibrosis, LVH, systolic function, renal function, incidence of worsening HF and mortality. This will test the potential beneficial effects of Dapagliflozin on myocyte function, interstitial fibrosis, LVH, systolic dysfunction, renal dysfunction, incidence of worsening HF and mortality in AS patients treated with TAVR. ;Secondary Objective: Not applicable;Primary end point(s): A composite endpoint of changes in LV mass, systolic function, eGFR, and serum Nt-proBNP - all parameters related to HF and adverse outcome in the AS setting is planned. Changes from baseline to 12 months of follow-up in at least 2 out of 4 well-known parameters of performance in AS is required to reach the primary endpoint. The level of change, in percentage points (%P), is considered clinically significant based on existing litterature: •LVMi reduction of 10 % point (by CMRI) •LV GLS absolute increase of 2.0 % point (by TTE) •A decrease in serum Nt-proBNP of more than 25% •Relative increase of 10% in eGFR ;Timepoint(s) of evaluation of this end point: The timepoint of evaluation is 12-months after transcatheter aortic valve replacement (TAVR). The values assessed at 12-months follow-up will be compared to the baseline measures (1-month before TAVR) to evaluate whether the patients meet the primary endpoint.	—

Measure

Time frame

Main Objective: The overall purpose of this study is to improve treatment of AS patients treated with TAVR. The study evaluates the effect of Dapagliflozin on mitochondrial function, myocardial fibrosis, LVH, systolic function, renal function, incidence of worsening HF and mortality. This will test the potential beneficial effects of Dapagliflozin on myocyte function, interstitial fibrosis, LVH, systolic dysfunction, renal dysfunction, incidence of worsening HF and mortality in AS patients treated with TAVR. ;Secondary Objective: Not applicable;Primary end point(s): A composite endpoint of changes in LV mass, systolic function, eGFR, and serum Nt-proBNP - all parameters related to HF and adverse outcome in the AS setting is planned. Changes from baseline to 12 months of follow-up in at least 2 out of 4 well-known parameters of performance in AS is required to reach the primary endpoint. The level of change, in percentage points (%P), is considered clinically significant based on existing litterature: •LVMi reduction of 10 % point (by CMRI) •LV GLS absolute increase of 2.0 % point (by TTE) •A decrease in serum Nt-proBNP of more than 25% •Relative increase of 10% in eGFR ;Timepoint(s) of evaluation of this end point: The timepoint of evaluation is 12-months after transcatheter aortic valve replacement (TAVR). The values assessed at 12-months follow-up will be compared to the baseline measures (1-month before TAVR) to evaluate whether the patients meet the primary endpoint.

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Secondary

Measure	Time frame
Secondary end point(s): 1. Difference in the change in eGFR from baseline to 12-months 2. Difference in eGFR at 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 4. The number of patients with a >10% decrease in cardiac fibrosis when assessed by histology and quantified by stereology (sub study) 5. The number of patients with an increase in the respiratory control ratio (RCR) by =10% measured by High Resolution Respirometry (HRR) (sub study) 6. Composite endpoint of worsening HF with hospitalization or urgent outpatient clinical visit due to HF, cardiovascular- and all-cause mortality 7. All-cause mortality 8. Worsening HF with hospitalization or urgent outpatient clinical visit due to HF 9. Difference in the change in urinary albumin/creatinine ratio (ACR) from baseline to 12-months. 10. Difference in ACR at 12-months. 11. 24-hour ambulatory blood pressure changes from baseline to 12 months. 12. Change from baseline to 12-months follow-up in the KCCQ Total Symptom Score 13. Change from baseline to 12-months follow-up in NYHA-class 14. LVMi reduction of 10 % point (by CMRI) from baseline to 12-months follow-up 15. LV GLS absolute increase of 2.0 % point (by TTE) from baseline to 12-months follow-up 16. A decrease in serum Nt-proBNP of more than 25% from baseline to 12-months follow-up 17. Relative increase of 10% in eGFR measured at baseline and 12-months Explorative endpoints. 1. Urinary excretion of fibrosis markers. 2. P-Pro Collagen III 3. P-PICP 4. P-Copeptin 5. Weight & body composition by Impedance measurement ;Timepoint(s) of evaluation of this end point: At 12-months follow-up after transcatheter aortic valve replacement.	—

Measure

Time frame

Secondary end point(s): 1. Difference in the change in eGFR from baseline to 12-months 2. Difference in eGFR at 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 4. The number of patients with a >10% decrease in cardiac fibrosis when assessed by histology and quantified by stereology (sub study) 5. The number of patients with an increase in the respiratory control ratio (RCR) by =10% measured by High Resolution Respirometry (HRR) (sub study) 6. Composite endpoint of worsening HF with hospitalization or urgent outpatient clinical visit due to HF, cardiovascular- and all-cause mortality 7. All-cause mortality 8. Worsening HF with hospitalization or urgent outpatient clinical visit due to HF 9. Difference in the change in urinary albumin/creatinine ratio (ACR) from baseline to 12-months. 10. Difference in ACR at 12-months. 11. 24-hour ambulatory blood pressure changes from baseline to 12 months. 12. Change from baseline to 12-months follow-up in the KCCQ Total Symptom Score 13. Change from baseline to 12-months follow-up in NYHA-class 14. LVMi reduction of 10 % point (by CMRI) from baseline to 12-months follow-up 15. LV GLS absolute increase of 2.0 % point (by TTE) from baseline to 12-months follow-up 16. A decrease in serum Nt-proBNP of more than 25% from baseline to 12-months follow-up 17. Relative increase of 10% in eGFR measured at baseline and 12-months Explorative endpoints. 1. Urinary excretion of fibrosis markers. 2. P-Pro Collagen III 3. P-PICP 4. P-Copeptin 5. Weight & body composition by Impedance measurement ;Timepoint(s) of evaluation of this end point: At 12-months follow-up after transcatheter aortic valve replacement.

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Countries

Denmark

Contacts

Public ContactDepartment of Cardiology

Aarhus University Hospital

Hjertesygdomme@auh.rm.dk4578 45 00 00

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026