Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy

Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy - A Randomized, Double-Blind, Placebo-Controlled, Crossover, Multicenter Trial

This study aims to evaluate the safety and effectiveness of Enavogliflozin 0.3 mg, an SGLT2 inhibitor, in patients with amyloid cardiomyopathy. Participants will take both the study drug and a placebo in two separate periods, with a wash-out period in between. The goal is to determine whether Enavogliflozin is safe and effective for treating amyloid cardiomyopathy.

Patients with a confirmed diagnosis of cardiac amyloidosis and symptomatic heart failure (NYHA class II-III) will be recruited.

Participants will be randomized to receive either the study drug or placebo and will undergo baseline and 12-week assessments, including the Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-minute walk test, and cardiopulmonary exercise testing. Following a 4-week washout period, participants will cross over to the alternate treatment arm (study drug or placebo) and repeat the same assessments at baseline and 12 weeks.

The primary endpoint will be the change in KCCQ Clinical Summary Score (KCCQ-CSS).

Inclusion Criteria:

1. Adults aged 19 years or older
2. Diagnosed with amyloid cardiomyopathy confirmed by cardiac biopsy or non-invasive imaging
3. Presence of heart failure symptoms corresponding to NYHA functional class II-III
4. Patients on stable oral diuretic use, without dose changes exceeding 50% of the previous dose, for at least 2 weeks prior to study enrollment
5. Ambulatory (able to walk)
6. Able to provide written informed consent for study participation

Exclusion Criteria:

1. Pregnant or breastfeeding women
2. Active infection
3. Major cardiovascular events (e.g., myocardial infarction, stroke) within the past 6 months
4. Scheduled for coronary revascularization, CRT-D implantation, atrial flutter/fibrillation ablation, or valve surgery
5. History of heart transplantation
6. Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² (calculated by CKD-EPI formula)
7. No history of cancer within the past 5 years at screening (except borderline cancers without recurrence for 2-3 years; multiple myeloma with cardiac involvement is classified as cardiac amyloidosis and is exempt)
8. Heart failure primarily caused by severe left sided valvular disease or ischemic heart disease (except if valvular disease is corrected)
9. Type 1 diabetes mellitus or insulin-dependent diabetes
10. History of ketoacidosis, complicated urinary or genital infections, or kidney stones
11. Systolic blood pressure < 80 mmHg or symptomatic hypotension
12. Major surgery within 90 days prior to enrollment
13. Known hypersensitivity or allergic reaction to the study drug or its components
14. Moderate to severe liver impairment
15. Chronic alcohol or substance abuse
16. Residing in long-term care facilities (e.g., nursing homes)
17. Unable to understand or comply with study drug, procedures, or follow-up, or who are deemed by the investigator to be unlikely to complete the study