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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Graz

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

7 Jan 2026 → ongoing

Decision date (initial)

2025-12-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Austrian Society of Cardiology

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess if in patients with HOCM and arterial hypertension, low dose HCT increases peak LVOT gradient at rest to a significantly lesser extent than valsartan

Secondary objectives 1

1. Evaluate the effect of low dose HCT compared to valsartan on: • Provocative LVOT obstruction • Left ventricular systolic pressure • Quality of life • Laboratory parameters • Exercise capacity (CPET sub-study)

Conditions and MedDRA coding

Hypertrophic cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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
2. SAM-associated LVOTO, defined as peak LVOT pressure gradient ≥ 30mmHg at rest assessed 30 to 60 minutes after standardized meal intake
3. 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
4. Treatment with cardioselective betablocker in maximally tolerated dose or intolerance/contraindication to betablocker
5. Age ≥ 18 years
6. 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
7. No additional contraceptive measures are required to be used for male participants
8. Willingness and ability to provide signed written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines.

Exclusion criteria 12

1. Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM, such as amyloidosis, Fabry disease, Noonan syndrome, or other HCM-phenocopies.
2. Women who are breastfeeding or pregnant
3. Any other serious condition that in the opinion of the investigator could prevent participation in the study.
4. Completed a study with an investigational device or drug <30 days or 5 half-lives to screening.
5. Enrolled in another study and receiving any investigational treatment (device or drug).
6. Current treatment or treatment within 2 weeks prior to randomization with either a thiazide diuretic or an angiotensin receptor blocker
7. Change in antihypertensive therapy within 2 weeks prior to randomization and up to the day of randomization.
8. Concomitant use of Aliskiren in patients with diabetes mellitus or renal disease (estimated glomerular filtration rate [eGFR] <60mL/min).
9. 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.
10. Initiation or change in myosin-inhibitor therapy 52 weeks prior to randomization or planned initiation during the active study period
11. Known allergy to HCT or valsartan or their constituents, or to medications with a similar chemical structure
12. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in absolute change of peak LVOT gradient at rest from before to after the treatment period between the two interventions

Secondary endpoints 12

1. Difference of absolute changes between the two intervention groups of Peak LVOT gradient after Valsalva-Maneuver
2. Difference of absolute changes between the two intervention groups of left ventricular systolic pressure calculated from brachial blood pressure and LVOT gradient
3. Difference of absolute changes between the two intervention groups of Kansas City Cardiomyopathy Questionnaire (KCCQ-23 Score)
4. Difference of absolute changes between the two intervention groups of EQ5D5L score
5. Difference of absolute changes between the two intervention groups of NT-proBNP
6. Difference of absolute changes between the two intervention groups of High-sensitive Troponin T/I
7. Difference of absolute changes between the two intervention groups of Interleukin-6
8. Difference of absolute changes between the two intervention groups of pVO2 during CPET (CPET sub-study)
9. Difference of absolute changes between the two intervention groups of mean systolic postprandial office blood pressure
10. Difference of absolute changes between the two intervention groups of mean diastolic postprandial office blood pressure
11. Number of serious adverse events (SAEs)
12. Difference of absolute changes between the two intervention groups of NYHA class

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Graz

Sponsor organisation

Medical University Of Graz

Address

Neue Stiftingtalstrasse 6

City

Graz

Postcode

8010

Country

Austria

Scientific contact point

Organisation

Medical University Of Graz

Contact name

Prof. Nicolas Verheyen

Public contact point

Organisation

Medical University Of Graz

Contact name

Prof. Nicolas Verheyen

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications