E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-obstructive Hypertrophic cardiomyopathy |
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E.1.1.1 | Medical condition in easily understood language |
Hypertrophic cardiomyopathy (HCM) is a condition in which a portion of the heart becomes thickened without an obvious cause. This results in the heart being less able to pump effectively. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007636 |
E.1.2 | Term | Cardiomyopathy |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049813 |
E.1.2 | Term | Non-obstructive cardiomyopathy |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020871 |
E.1.2 | Term | Hypertrophic cardiomyopathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061029 |
E.1.2 | Term | Cardiomyopathy primary |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We want to quantify the effect of Bisoprolol and Verapamil on myocardial function, hemodynamics and symptoms in patients with non-obstructive hypertrophic cardiomyopathy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal exclusion criteria |
- Left ventricular ejection fraction < 50% - LVOT gradient >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 < 60 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 CMR 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- The incidence of non-sustained ventricular tachycardia (NSVT) is different (Hazard ratio ≥ 0.5) between treatments in non-obstructive HCM patients. - The left ventricular outflow tract (LVOT) time velocity integral (VTI) is different (ΔVTI ≥1 cm) between treatments in non-obstructive HCM patients. - The maximal oxygen consumption (VO2 max) is different (ΔVO2 max ≥1 ml/kg/min) between treatments in non-obstructive HCM patients
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The randomization codes will be unblinded when more than 57 patients tested with CPX has finished full trial participation. This, in order to analyze the hemodynamic and functional endpoints and to perform interim analyses of event rates in the ambulatory ECG monitoring. Final endpoint evaluation is estimated to about 24 months after the first patient have been enrolled. |
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E.5.2 | Secondary end point(s) |
- Kansas City Cardiomyopathy Questionnaire (KCCQ) score - New York Heart Association (NYHA) class - Canadian Cardiovascular Society (CCS) Klassifikation til vurdering af brystsmerter - Pro-BNP/BNP - High sensitive Troponin I/Troponin T - Metabolic equivalent of task (METs) - Recovery time - Anaerobe threshold - Left ventricular end-diastolic dimension (Echocardiography) - Strain in hypertrophied segment (Echocardiography) - Strain in non-hypertrophied segment (Echocardiography) - Left atrial dimension (Echocardiography) - Atrial fibrillation (Ambulatory ECG monitoring) - Estimation of ventricular ectopic beats (Ambulatory ECG monitoring)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The randomization codes will be unblinded when more than 57 patients tested with CPX has finished full trial participation. This, in order to analyze the hemodynamic and functional endpoints and to perform interim analyses of event rates in the ambulatory ECG monitoring. Final endpoint evaluation is estimated to about 24 months after the first patient have been enrolled. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |