HYDrochlorothiazidE compared to valsartan to treat arterial hypertension in patients with Hypertrophic obstructive CardioMyopathy – the HYDE-HCM Trial

Prior treatment

• Initiation or change in myosin-inhibitor therapy 52 weeks prior to randomization or planned initiation during the active study period
• Completed a study with an investigational device or drug <30 days or 5 half-lives to screening.
• Enrolled in another study and receiving any investigational treatment (device or drug).
• Current treatment or treatment within 2 weeks prior to randomization with either a thiazide diuretic or an angiotensin receptor blocker
• Change in antihypertensive therapy within 2 weeks prior to randomization and up to the day of randomization.
• Invasive septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) within 6 months prior to screening or planned invasive septal reduction therapy during the study.

Other illness

• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM, such as amyloidosis, Fabry disease, Noonan syndrome, or other HCM-phenocopies.
• Known allergy to HCT or valsartan or their constituents, or to medications with a similar chemical structure
• Any other serious condition that in the opinion of the investigator could prevent participation in the study.

Lab values

• Any other contraindication for treatment with either HCT or valsartan, including: • eGFR <30mL/min and/or serum creatinine >1.8mg/100mL • acute glomerulonephritis • severe hepatic zirrhosis or failure, hepatic precoma/coma • systolic blood pressure <90mmHg • heart rate <50bpm • sodium <130mmol/L • total calcium >2.65mmol/L • gout • second and third trimester of pregnancy
• Concomitant use of Aliskiren in patients with diabetes mellitus or renal disease (estimated glomerular filtration rate [eGFR] <60mL/min).

Other

• Women who are breastfeeding or pregnant

• Diagnosis of HCM consistent with the current Guidelines of the European Society of Cardiology and American College of Cardiology Foundation/American Heart Association: presence of increased left ventricular wall thickness (≥15mm or ≥13mm with positive family history of HCM) in any myocardial segment that is not explained solely by loading conditions
• SAM-associated LVOTO, defined as peak LVOT pressure gradient ≥ 30mmHg at rest assessed 30 to 60 minutes after standardized meal intake
• Fasting office blood pressure ≥ 135/85 mmHg (either systolic or diastolic BP increased), measured as standardized office blood pressure after at least six hours of fasting
• Treatment with cardioselective betablocker in maximally tolerated dose or intolerance/contraindication to betablocker
• Age ≥ 18 years
• Female participants are eligible to participate if they are not pregnant or breastfeeding, and at least 1 of the following conditions applies: o is not a women of childbearing potential (WOCBP) or o is a WOCBP and using a contraceptive method that is highly effective (failure rate <1% per year) during the intervention period
• No additional contraceptive measures are required to be used for male participants
• Willingness and ability to provide signed written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines.