bisoprolol fumarate, hydrochlorothiazide for Non-obstructive hypertrophic cardiomyopathy

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Maximal wall thickness ≥ 15 mm unrelated to hypertension, valve diseases or storage diseases."}
• {"criterion_text":"- And one of the following: 1. New York Heart Association – functional class (NYHA) ≥ II 2. A history of NYHA class ≥ II before treatment with BB or CCB 3. Pro-BNP>300 ng/l/35>nmol/l or BNP >100ng/l/>29nmol/l 4. Non-sustained VT (>120 min-1, ≥3 cycles) documented within the last 2 years of screening"}

Exclusion criteria

• {"criterion_text":"- Left ventricular ejection fraction < 50%"}
• {"criterion_text":"- Significant liver failure, severe valvular disease, bradycardia (40bpm) or hypotension (systolic <100mmHg), other significant comorbidity or risks associated with discontinuation of BB or CCB after individual judgement by the investigators."}
• {"criterion_text":"- Unable to understand patient information intellectually or linguistically"}
• {"criterion_text":"- Unable to perform exercise test."}
• {"criterion_text":"- Unable to speak and/or understand Danish."}
• {"criterion_text":"- Additional exclusion criteria for CMRI sub-study: 1.Implantable cardioverter defibrillator (any kind): 2.Pacemaker (any kind): 3.Metal implants like to affect image quality: 4.Metal implants that poses a risk during CMRI: 5.Inability to cope with being in the scanner."}
• {"criterion_text":"- LVOT gradient >30 mmHg at rest or during Valsalva maneuver after discontinuation of BB or CCB respectively"}
• {"criterion_text":"- History of LVOT gradient >30 mmHg at rest, during exercise or during Valsalva maneuver."}
• {"criterion_text":"- Permanent atrial fibrillation"}
• {"criterion_text":"- Permanent right ventricular pacing"}
• {"criterion_text":"- Previous intolerance for Bisoprolol (BB) or Verapamil (CCB)"}
• {"criterion_text":"- Known present obstructive coronary disease (previous percutaneous coronary intervention is accepted)"}
• {"criterion_text":"- eGFR < 40 ml/min"}
• {"criterion_text":"- Fertile women (<50 years) who are pregnant (Positive Plasma-HCG), breastfeeding or not using anticonceptions."}

Primary endpoints

• {"endpoint_text":"- Phase 1: The maximal oxygen consumption (VO2 max) is different (ΔVO2 max ≥1 ml/kg/min) between treatments in non-obstructive HCM patients","definition_or_measurement_approach":"Difference in maximal oxygen consumption (ΔVO2 max ≥1 ml/kg/min) between treatments (VO2 max measured as stated in endpoint)."}
• {"endpoint_text":"- Phase 2: The left ventricular enddiastolic volume (LVvol) is different (ΔLVvol ≥3 ml) between treatments in non-obstructive HCM patients.","definition_or_measurement_approach":"Difference in left ventricular end-diastolic volume (ΔLVvol ≥3 ml) between treatments."}
• {"endpoint_text":"- Phase 3: The incidence of non-sustained ventricular tachycardia (NSVT) is different (Hazard ratio ≥ 0.5) between treatments in non-obstructive HCM patients.","definition_or_measurement_approach":"Incidence of NSVT compared between treatments with target effect expressed as Hazard ratio ≥ 0.5."}

Secondary endpoints

• {"endpoint_text":"- Sex specific analyses of effect parameters","definition_or_measurement_approach":""}
• {"endpoint_text":"- Kansas City Cardiomyopathy Questionnaire (KCCQ) score","definition_or_measurement_approach":"KCCQ standardized patient-reported outcome score (questionnaire)."}
• {"endpoint_text":"- New York Heart Association (NYHA) functional classification","definition_or_measurement_approach":"NYHA functional class assessment."}
• {"endpoint_text":"- Canadian Cardiovascular Society (CCS)","definition_or_measurement_approach":"CCS angina classification."}
• {"endpoint_text":"- Tolerable dose","definition_or_measurement_approach":""}
• {"endpoint_text":"- Pro-BNP/BNP","definition_or_measurement_approach":"Blood measurement of Pro-BNP/BNP biomarkers."}
• {"endpoint_text":"- High sensitive Troponin I/Troponin T","definition_or_measurement_approach":"Blood measurement of high-sensitivity troponin I or T."}
• {"endpoint_text":"- Recovery time during CPET","definition_or_measurement_approach":"Measured during cardiopulmonary exercise testing (CPET)."}
• {"endpoint_text":"- VO2 max at anaerobic threshold during CPET","definition_or_measurement_approach":"Measured during CPET at anaerobic threshold."}
• {"endpoint_text":"- Percent predicted VO2 max during CPET","definition_or_measurement_approach":"Measured during CPET as percent predicted VO2 max."}
• {"endpoint_text":"- Ventilatory equivalent for carbon dioxide VE/VCO2 during CPET","definition_or_measurement_approach":"Measured during CPET (VE/VCO2)."}
• {"endpoint_text":"- Metabolic equivalent of task (METs) during CPET","definition_or_measurement_approach":"Measured during CPET (METs)."}
• {"endpoint_text":"- Left ventricular end-diastolic dimension during echocardiography","definition_or_measurement_approach":"Measured by echocardiography."}
• {"endpoint_text":"- Myocardial deformation imaging (Strain) during echocardiography","definition_or_measurement_approach":"Echocardiographic strain imaging."}
• {"endpoint_text":"- Left ventricular outflow tract time velocity intergral (VTI) during echocardiography","definition_or_measurement_approach":"Measured by echocardiography (VTI)."}
• {"endpoint_text":"- Left atrial dimension during echocardiography","definition_or_measurement_approach":"Measured by echocardiography."}
• {"endpoint_text":"- Left ventricular systolic function during CMRI","definition_or_measurement_approach":"Measured by cardiac MRI (CMRI)."}
• {"endpoint_text":"- Right ventricular dimensions during CMRI","definition_or_measurement_approach":"Measured by CMRI."}
• {"endpoint_text":"- Right ventricular systolic function during CMRI","definition_or_measurement_approach":"Measured by CMRI."}
• {"endpoint_text":"- Stroke volume (Aortic flow) during CMRI","definition_or_measurement_approach":"Measured by CMRI (aortic flow measurement)."}
• {"endpoint_text":"- Coronary sinus flow during CMRI","definition_or_measurement_approach":"Measured by CMRI."}
• {"endpoint_text":"- Dimension of inferior and superior caval vein during CMRI","definition_or_measurement_approach":"Measured by CMRI."}
• {"endpoint_text":"- Left atrial dimension during CMRI","definition_or_measurement_approach":"Measured by CMRI."}
• {"endpoint_text":"- Atrial fibrillation (Ambulatory ECG monitoring)","definition_or_measurement_approach":"Assessed via ambulatory ECG monitoring."}
• {"endpoint_text":"- Estimation of ventricular ectopic beats (Ambulatory ECG monitoring)","definition_or_measurement_approach":"Assessed via ambulatory ECG monitoring."}

Denmark

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

04-07-2024

Processing Time Days

14

Number Of Sites

4

Number Of Participants

140

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":"sponsor duties code 1","organisation_type":"Educational Institution"}