Dapagliflozin in Patients With Non-Obstructive Hypertrophic Cardiomyopathy: A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Korábbi kezelés

• History of hypersensitivity to the investigational product.
• Presence of a cardiac implantable electronic device (CIED), except for an implantable cardioverter-defibrillator (ICD) implanted at least 3 months before informed consent.
• Severe aortic stenosis or mitral stenosis with a potential need for surgical intervention during the study period.
• Candidates for heart transplantation or recipients of a previous heart transplantation.
• Active malignancy receiving chemotherapy, radiation therapy, or surgical treatment, or life expectancy of less than 1 year.
• Participation in another investigational drug or medical device study, or participation in such a study within 30 days prior to screening.

Más betegség

• Uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg) or severe hypotension (systolic blood pressure <90 mmHg).
• Type 1 diabetes mellitus or history of diabetic ketoacidosis.
• New York Heart Association (NYHA) Class IV.

Laborértékek

• Current treatment with an SGLT2 inhibitor or use within 4 weeks prior to screening. (For participants with diabetes mellitus, use of glucose-lowering medications other than SGLT2 inhibitors is permitted.)
• End-stage renal disease requiring dialysis or chronic kidney disease with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m².
• AST or ALT >3 times the upper limit of normal, history of hepatic encephalopathy, esophageal varices, or portocaval shunt surgery.
• Conditions that may confound the assessment of heart failure symptoms, including severe anemia (hemoglobin <7 g/dL), uncontrolled arrhythmias, severe pulmonary disease, or other conditions judged by the investigator to interfere with study assessments.
• Hereditary intolerance to lactose anhydrous, including galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Egyéb

• Inability to perform cardiopulmonary exercise testing (CPET).
• Current pregnancy or breastfeeding.
• Untreated alcohol abuse or substance abuse.

• Able to understand the study protocol and provide written informed consent.
• Adults aged 19 to 80 years.
• Nondiabetic participants or participants with type 2 diabetes mellitus (HbA1c 6.5% to 10.5%).
• Patients with nonobstructive hypertrophic cardiomyopathy (HCM) documented by echocardiography performed within 3 months prior to screening, with no significant dynamic left ventricular outflow tract (LVOT) obstruction at rest, during the Valsalva maneuver, or with exercise provocation.
  • Nonobstructive HCM defined as a maximum LVOT pressure gradient <30 mmHg.
  • Maximum left ventricular wall thickness ≥15 mm in participants without a family history of HCM, or ≥13 mm in participants with a family history of HCM or a pathogenic HCM-associated genetic variant.
• Participants receiving medical therapy for HCM, including beta-blockers, non-dihydropyridine calcium channel blockers, loop diuretics, thiazide or thiazide-like diuretics, mineralocorticoid receptor antagonists, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors, must have been on a stable dose for at least 2 weeks prior to randomization and be expected to remain on a stable dose throughout the study period.
• Women of childbearing potential who agree to use effective contraception