Overview
Sponsor-declared trial summary
Non-obstructive hypertrophic cardiomyopathy
The overall clinical purpose and the purpose of this study is to reduce the symptomatic burden and arrhythmic complications in patients with HCM. We aim 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 v…
Key facts
- Sponsor
- Region Midtjylland
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 1 Aug 2022 → ongoing
- Decision date (initial)
- 2024-07-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Novo Nordisk Foundation · Danske Regioners medicin og behandlingspulje
External identifiers
- EU CT number
- 2024-515346-17-00
- EudraCT number
- 2021-006953-77
- ClinicalTrials.gov
- NCT05569382
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The overall clinical purpose and the purpose of this study is to reduce the symptomatic burden and arrhythmic complications in patients with HCM.
We aim 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.
Conditions and MedDRA coding
Non-obstructive hypertrophic cardiomyopathy
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- 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
Exclusion criteria 14
- Left ventricular ejection fraction < 50%
- LVOT gradient >30 mmHg at rest or during Valsalva maneuver after discontinuation of BB or CCB respectively
- 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: 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.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Phase 1: The maximal oxygen consumption (VO2 max) is different (ΔVO2 max ≥1 ml/kg/min) between treatments in non-obstructive HCM patients
- Phase 2: The left ventricular enddiastolic volume (LVvol) is different (ΔLVvol ≥3 ml) 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.
Secondary endpoints 25
- 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
- Pro-BNP/BNP
- High sensitive Troponin I/Troponin T
- Recovery time during CPET
- VO2 max at anaerobic threshold during CPET
- Percent predicted VO2 max during CPET
- Ventilatory equivalent for carbon dioxide VE/VCO2 during CPET
- Metabolic equivalent of task (METs) during CPET
- Left ventricular end-diastolic dimension during echocardiography
- Myocardial deformation imaging (Strain) during echocardiography
- Left ventricular outflow tract time velocity intergral (VTI) during echocardiography
- Left atrial dimension during echocardiography
- Left ventricular systolic function during CMRI
- Right ventricular dimensions during CMRI
- Right ventricular systolic function during CMRI
- Stroke volume (Aortic flow) during CMRI
- Coronary sinus flow during CMRI
- Dimension of inferior and superior caval vein during CMRI
- Left atrial dimension during CMRI
- Atrial fibrillation (Ambulatory ECG monitoring)
- Estimation of ventricular ectopic beats (Ambulatory ECG monitoring)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SCP1068778 · ATC
- Active substance
- Verapamil
- Route of administration
- ORAL
- Max daily dose
- 360 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 3 Week(s)
- Authorisation status
- Authorised
- ATC code
- C08DA01 — VERAPAMIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Capsulation
SCP1126442 · ATC
- Active substance
- Bisoprolol Fumarate
- Route of administration
- ORAL
- Max daily dose
- 7.5 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 3 Week(s)
- Authorisation status
- Authorised
- ATC code
- C07AB07 — BISOPROLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Capsulation
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Region Midtjylland
- Sponsor organisation
- Region Midtjylland
- Address
- Palle Juul-Jensens Boulevard 99
- City
- Aarhus N
- Postcode
- 8200
- Country
- Denmark
Scientific contact point
- Organisation
- Aarhus Universitetshospital
- Contact name
- Louise Bjerregaard
Public contact point
- Organisation
- Aarhus Universitetshospital
- Contact name
- Morten Steen Kvistholm Jensen
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Aarhus Universitet ORG-100028380
|
Aarhus N, Denmark | On site monitoring |
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 140 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2022-08-01 | 2022-08-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 3 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protokol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Placeholder | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Placeholder | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-13 | Denmark | Acceptable 2024-06-28
|
2024-07-04 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-02-13 | Denmark | Acceptable 2025-02-14
|
2025-02-14 |