DAPAGLIFLOZIN for Aortic stenosis

Inclusion criteria

• {"criterion_text":"- 1. Signed informed consent\n- 2. Scheduled TAVR for significant symptomatic AS according to current guidelines\n- 3. Age < 18 years and < 85 years.\n- 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)\n- 5. eGFR > 30 mL/min/1.73 m2"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- 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: •\tLVMi reduction of 10 % point (by CMRI) •\tLV GLS absolute increase of 2.0 % point (by TTE) •\tA decrease in serum Nt-proBNP of more than 25% •\tRelative increase of 10% in eGFR","definition_or_measurement_approach":"Change from baseline to 12 months. LVMi measured by CMRI (CMR). LV GLS measured by transthoracic echocardiography (TTE). Serum Nt-proBNP measured by blood test. eGFR measured by standard renal function tests."}

Secondary endpoints

• {"endpoint_text":"- 1.\tDifference in the change in eGFR from baseline to 12-months","definition_or_measurement_approach":"Change in eGFR measured from baseline to 12 months."}
• {"endpoint_text":"- 2.\tDifference in eGFR at 12-months.","definition_or_measurement_approach":"eGFR measured at 12 months."}
• {"endpoint_text":"- 3.\tThe 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","definition_or_measurement_approach":"Myocardial interstitial fibrosis assessed by extracellular volume (ECV) using late gadolinium enhancement CMR; outcome is number of patients with ≥10% relative difference."}
• {"endpoint_text":"- 4.\tThe number of patients with a >10% decrease in cardiac fibrosis when assessed by CMR using native T1-mapping.","definition_or_measurement_approach":"Cardiac fibrosis assessed by native T1-mapping on CMR; outcome is number of patients with >10% decrease."}
• {"endpoint_text":"- 5.\tComposite endpoint of worsening HF with hospitalization or urgent outpatient clinical visit due to HF, and all-cause mortality","definition_or_measurement_approach":"Composite clinical events endpoint including HF hospitalization or urgent HF outpatient visit and all-cause mortality."}
• {"endpoint_text":"- 6.\tAll-cause mortality","definition_or_measurement_approach":"All-cause mortality recorded during follow-up."}
• {"endpoint_text":"- 7.\tWorsening HF with hospitalization or urgent outpatient clinical visit due to HF","definition_or_measurement_approach":"Clinical event of worsening heart failure leading to hospitalization or urgent outpatient visit."}
• {"endpoint_text":"- 8.\tDifference in the change in urinary albumin/creatinine ratio (ACR) from baseline to 12-months.","definition_or_measurement_approach":"Change in urinary ACR from baseline to 12 months."}
• {"endpoint_text":"- 9.\tDifference in ACR at 12-months.","definition_or_measurement_approach":"Urinary ACR measured at 12 months."}
• {"endpoint_text":"- 10.\t24-hour ambulatory blood pressure changes from baseline to 12 months.","definition_or_measurement_approach":"24-hour ambulatory blood pressure monitoring change from baseline to 12 months."}
• {"endpoint_text":"- 11.\tChange from baseline to 12-months follow-up in the KCCQ Total Symptom Score","definition_or_measurement_approach":"Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score change from baseline to 12 months."}
• {"endpoint_text":"- 12.\tChange from baseline to 12-months follow-up in NYHA-class","definition_or_measurement_approach":"Change in New York Heart Association (NYHA) class from baseline to 12 months."}
• {"endpoint_text":"- 13.\tLVMi reduction of 10 % point (by CMRI) from baseline to 12-months follow-up","definition_or_measurement_approach":"Left ventricular mass index (LVMi) measured by CMRI; outcome is 10% reduction from baseline at 12 months."}
• {"endpoint_text":"- 14.\tLV GLS absolute increase of 2.0 % point (by TTE) from baseline to 12-months follow-up","definition_or_measurement_approach":"Left ventricular global longitudinal strain (LV GLS) measured by TTE; outcome is absolute increase of 2.0 percentage points from baseline to 12 months."}
• {"endpoint_text":"- 15.\tA decrease in serum Nt-proBNP of more than 25% from baseline to 12-months follow-up","definition_or_measurement_approach":"Serum Nt-proBNP measured by blood test; outcome is >25% decrease from baseline to 12 months."}
• {"endpoint_text":"- 16.\tRelative increase of 10% in eGFR measured at baseline and 12-months","definition_or_measurement_approach":"eGFR measured at baseline and at 12 months; outcome is relative increase of 10%."}

Denmark

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

06-03-2025

Processing Time Days

259

Number Of Sites

1

Number Of Participants

76

Primary sponsor

Full Name

Region Midtjylland

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Educational Institution"}