The effect of Bisoprolol and Verapamil in non-obstructive hypertrophic cardiomyopathy

Treatment effects of Bisoprolol and Verapamil in symptomatic patients with non-obstructive hypertrophic cardiomyopathy - TEMPO II

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-006953-77-DK

Enrollment

140

Registered

2022-01-31

Start date

2022-04-11

Completion date

Unknown

Last updated

2024-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-obstructive Hypertrophic cardiomyopathy MedDRA version: 20.0 Level: PT Classification code 10007636 Term: Cardiomyopathy System Organ Class: 10007541 - Cardiac disorders MedDRA version: 20.0 Level: PT Classification code 10049813 Term: Non-obstructive cardiomyopathy System Organ Class: 10007541 - Cardiac disorders MedDRA version: 27.0 Level: PT Classification code 10020871 Term: Hypertrophic cardiomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA v

Interventions

Trade Name: Bisoprolol Pharmaceutical Form: Modified-release tablet INN or Proposed INN: BISOPROLOL CAS Number: 66722-44-9 Concentration unit: mg milligram(s) Concentration type: equal Concentration

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Informed consent - Age = 18 years - Maximal wall thickness = 15 mm unrelated to hypertension, valve diseases or storage diseases. - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40

Exclusion criteria

Exclusion criteria: - Left ventricular ejection fraction 30 mmHg at rest or during Valsalva maneuver after discontinuation of BB or CCB respectively - Previous history of LVOT gradient >30 mmHg at rest, during exercise or during Valsalva maneuver. - Permanent atrial fibrillation - Permanent right ventricular pacing - Previous intolerance for Bisoprolol (BB) or Verapamil (CCB) - Known present obstructive coronary disease (previous percutaneous coronary intervention is accepted) - eGFR < 40 ml/min - Fertile women (<50 years) who are pregnant (Positive Plasma-HCG), breastfeeding or not using anticonceptions. - 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. - Unable to understand patient information intellectually or linguistically - Unable to perform exercise test. - Unable to speak and/or understand Danish. Additional exclusion criteria for CMRI sub-study: - Implantable cardioverter defibrillator (any kind) - Pacemaker (any kind) - Metal implants like to affect image quality - Metal implants that poses a risk during CMR - Inability to cope with being in the scanner.

Design outcomes

Primary

Measure	Time frame
Main Objective: We want to quantify the effect of Bisoprolol and Verapamil on maximal oxygen consumption (VO2 max), left ventricular end diastolic volume and the incidence of non-sustained ventricular tachycardia in patients with non-obstructive hypertrophic cardiomyopathy. ;Secondary Objective: Not Applicable;Primary end point(s): - Phase 1: The maximal oxygen consumption (VO2 max) is different (?VO2 max =1 ml/kg/min) between treatments in non-obstructive HCM patients - Phase 2: The left ventricular end diastolic volume (LV vol) is different between treatments in non-obstructive HCM patients. - Phase 3: The incidence of non-sustained ventricular tachycardia (NSVT) is different (Hazard ratio = 0.5) between treatments in non-obstructive HCM patients. ;Timepoint(s) of evaluation of this end point: - Phase 1: The team may decide to unblind the treatment in patients, who are tested with CPX, after minimum 26 patients have completed all three treatment periods. Interim analyses of event rates in the ambulatory ECG monitoring (Phase three) will be performed and an adjusted sample size calculation for the arrhythmic endpoint may be applied (Ultimo 2024) - Phase 2: The team may decide to unblind the treatment in all patients after 30-50 patients have finished the CMRI in all three treatment periods. (Ultimo 2025) - Phase 3: The team may decide to unblind the remaining patients, after 82-140 patients have finished the study. A different sample size may be applied after interim analyses of event rates in phase one. (Ultimo 2026)	—

Measure

Time frame

Main Objective: We want to quantify the effect of Bisoprolol and Verapamil on maximal oxygen consumption (VO2 max), left ventricular end diastolic volume and the incidence of non-sustained ventricular tachycardia in patients with non-obstructive hypertrophic cardiomyopathy. ;Secondary Objective: Not Applicable;Primary end point(s): - Phase 1: The maximal oxygen consumption (VO2 max) is different (?VO2 max =1 ml/kg/min) between treatments in non-obstructive HCM patients - Phase 2: The left ventricular end diastolic volume (LV vol) is different between treatments in non-obstructive HCM patients. - Phase 3: The incidence of non-sustained ventricular tachycardia (NSVT) is different (Hazard ratio = 0.5) between treatments in non-obstructive HCM patients. ;Timepoint(s) of evaluation of this end point: - Phase 1: The team may decide to unblind the treatment in patients, who are tested with CPX, after minimum 26 patients have completed all three treatment periods. Interim analyses of event rates in the ambulatory ECG monitoring (Phase three) will be performed and an adjusted sample size calculation for the arrhythmic endpoint may be applied (Ultimo 2024) - Phase 2: The team may decide to unblind the treatment in all patients after 30-50 patients have finished the CMRI in all three treatment periods. (Ultimo 2025) - Phase 3: The team may decide to unblind the remaining patients, after 82-140 patients have finished the study. A different sample size may be applied after interim analyses of event rates in phase one. (Ultimo 2026)

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Secondary

Measure	Time frame
Secondary end point(s): Clinical - Sex specific analyses of effect parameters - Kansas City Cardiomyopathy Questionnaire (KCCQ) score - New York Heart Association (NYHA) functional classification - Canadian Cardiovascular Society (CCS) - Tolerable dose Biomarkers - Pro-BNP/BNP - High sensitive Troponin I/Troponin T Cardiopulmonary exercise test - Recovery time - VO2 max at anaerobic threshold - Percent predicted VO2 max - Ventilatory equivalent for carbon dioxide VE/VCO2 - Metabolic equivalent of task (METs) Echocardiography - Left ventricular end-diastolic dimension - Myocardial deformation imaging (Strain) - Left ventricular outflow tract time velocity intergral (VTI) - Left atrial dimension Cardiac magnetic resonance imaging sub-study (optional) - Left ventricular systolic function - Right ventricular dimensions - Right ventricular systolic function - Stroke volume (Aortic flow) - Coronary sinus flow - Dimension of inferior and superior caval vein - Left atrial dimension Ambulatory ECG recordings - Atrial fibrillation (Ambulatory ECG monitoring) - Estimation of ventricular ectopic beats (Ambulatory ECG monitoring) ;Timepoint(s) of evaluation of this end point: - Phase 1: The team may decide to unblind the treatment in patients, who are tested with CPX, after minimum 26 patients have completed all three treatment periods. Interim analyses of event rates in the ambulatory ECG monitoring (Phase three) will be performed and an adjusted sample size calculation for the arrhythmic endpoint may be applied (Ultimo 2024) - Phase 2: The team may decide to unblind the treatment in all patients after 30-50 patients have finished the CMRI in all three treatment periods. (Ultimo 2025) - Phase 3: The team may decide to unblind the remaining patients, after 82-140 patients have finished the study. A different sample size may be applied after interim analyses of event rates in phase one. (Ultimo 2026)	—

Measure

Time frame

Secondary end point(s): Clinical - Sex specific analyses of effect parameters - Kansas City Cardiomyopathy Questionnaire (KCCQ) score - New York Heart Association (NYHA) functional classification - Canadian Cardiovascular Society (CCS) - Tolerable dose Biomarkers - Pro-BNP/BNP - High sensitive Troponin I/Troponin T Cardiopulmonary exercise test - Recovery time - VO2 max at anaerobic threshold - Percent predicted VO2 max - Ventilatory equivalent for carbon dioxide VE/VCO2 - Metabolic equivalent of task (METs) Echocardiography - Left ventricular end-diastolic dimension - Myocardial deformation imaging (Strain) - Left ventricular outflow tract time velocity intergral (VTI) - Left atrial dimension Cardiac magnetic resonance imaging sub-study (optional) - Left ventricular systolic function - Right ventricular dimensions - Right ventricular systolic function - Stroke volume (Aortic flow) - Coronary sinus flow - Dimension of inferior and superior caval vein - Left atrial dimension Ambulatory ECG recordings - Atrial fibrillation (Ambulatory ECG monitoring) - Estimation of ventricular ectopic beats (Ambulatory ECG monitoring) ;Timepoint(s) of evaluation of this end point: - Phase 1: The team may decide to unblind the treatment in patients, who are tested with CPX, after minimum 26 patients have completed all three treatment periods. Interim analyses of event rates in the ambulatory ECG monitoring (Phase three) will be performed and an adjusted sample size calculation for the arrhythmic endpoint may be applied (Ultimo 2024) - Phase 2: The team may decide to unblind the treatment in all patients after 30-50 patients have finished the CMRI in all three treatment periods. (Ultimo 2025) - Phase 3: The team may decide to unblind the remaining patients, after 82-140 patients have finished the study. A different sample size may be applied after interim analyses of event rates in phase one. (Ultimo 2026)

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Countries

Denmark

Contacts

Public ContactMorten Steen Kvistholm Jensen

Aarhus University Hospital

004540145482

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026