Clinical trial • Not applicable • Cardiology

PROPRANOLOL HYDROCHLORIDE for Andersen-Tawil syndrome|Multifocal ectopic Purkinje-related premature contractions

Not applicable trial of PROPRANOLOL HYDROCHLORIDE for Andersen-Tawil syndrome|Multifocal ectopic Purkinje-related premature contractions.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Andersen-Tawil syndrome|Multifocal ectopic Purkinje-related premature contractions
Trial Stage
Not applicable
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
04-03-2024
First CTIS Authorization Date
10-06-2024

Trial design

Flecainide monotherapy compared with combination therapy of flecainide plus beta-blockers or calcium channel blockers; for MEPPC patients, quinidine compared with flecainide in phase 2. Specific arm doses/schedules not specified in the CTIS record.-controlled Not applicable trial across 1 site in Netherlands.

Comparator
Flecainide monotherapy compared with combination therapy of flecainide plus beta-blockers or calcium channel blockers; for MEPPC patients, quinidine compared with flecainide in phase 2. Specific arm doses/schedules not specified in the CTIS record.
Biomarker Stratified
True; SCN5A class 4 or 5 variant carrier (MEPPC inclusion criterion)
Target Sample Size
10

Eligibility

Recruits 10 No vulnerable populations selected. Minimum age ≥ 18 years; 'Inability to provide informed consent' is listed as an exclusion..

Pregnancy Exclusion
Pregnancy
Vulnerable Population
No vulnerable populations selected. Minimum age ≥ 18 years; 'Inability to provide informed consent' is listed as an exclusion.

Inclusion criteria

  • {"criterion_text":"- One of the following two primary diagnostic criteria A.\tClinical diagnosis of ATS. Genetically confirmed diagnosis (i.e. class 4 or 5 KCNJ2 variant) is not required B.\tClinical diagnosis of MEPPC and carrier of associated class 4 or 5 SCN5A variant"}
  • {"criterion_text":"- Has demonstrated a disease phenotype of ATS or MEPPC including ventricular arrhythmia burden at any point during follow-up on Holter monitor or other rhythm monitoring device (i.e. loop recorder, ECG patch)"}
  • {"criterion_text":"- Is currently treated with a stable (at least 3 months) dose of flecainide"}
  • {"criterion_text":"- Age ≥ 18 years"}

Exclusion criteria

  • {"criterion_text":"- Pregnancy"}
  • {"criterion_text":"- Inability to take orally administered tablets"}
  • {"criterion_text":"- Inability to provide informed consent"}
  • {"criterion_text":"- Contra-indication to study medication"}
  • {"criterion_text":"- Significant structural heart disease (left ventricular ejection fraction <50%, history or signs of coronary ischemia, suspicion or definitive diagnosis of cardiomyopathy, or moderate/severe valve regurgitation)"}
  • {"criterion_text":"- Suspicion or definitive diagnosis of another (heritable) arrhythmia syndrome, e.g. Brugada syndrome, early repolarization syndrome or catecholaminergic polymorphic ventricular tachycardia"}
  • {"criterion_text":"- Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT interval on the resting ECG at baseline"}
  • {"criterion_text":"- History of therapy refractory ventricular arrhythmia or intolerable side-effects on an adequate dose of any study medication, as determined by the treating cardiologist"}
  • {"criterion_text":"- Serious known comorbid disease with a life expectancy of less than two years"}
  • {"criterion_text":"- Ongoing medical condition that is deemed by the principal investigator to interfere with the conduct or assessments of the study or safety of the subjects"}
  • {"criterion_text":"- Circumstances that prevent follow-up"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The ventricular ectopy burden per 24-hour period.","definition_or_measurement_approach":"Measured as ventricular ectopy burden per 24-hour period using 24-hour electrocardiographic monitoring (Holter or ECG patch); standard 12-lead ECG also performed per protocol."}

Recruitment

Planned Sample Size
10
Recruitment Window Months
13
Consent Approach
Informed consent must be provided by participants; minimum age is ≥ 18 years. 'Inability to provide informed consent' is an exclusion. No details on assent, age-specific documents, or languages are provided.

Geography

Total Number Of Sites
1
Total Number Of Participants
10

Netherlands

Earliest CTIS Part Ii Submission Date
11-05-2024
Latest Decision Or Authorization Date
10-06-2024
Processing Time Days
30
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Amsterdam UMC
Department Name
Cardiology
Principal Investigator Name
Christian van der Werf
Principal Investigator Email
c.vanderwerf@amsterdamumc.nl
Contact Person Name
Christian van der Werf
Contact Person Email
c.vanderwerf@amsterdamumc.nl
Number Of Participants
10

Sponsor

Primary sponsor

Full Name
Amsterdam UMC
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Netherlands

Investigational products

Investigational Product Name
PROPRANOLOL
Active Substance
PROPRANOLOL HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
160 mg
Investigational Product Name
ATENOLOL
Active Substance
ATENOLOL, CHLORTALIDONE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
100 mg
Investigational Product Name
NEBIVOLOL
Active Substance
NEBIVOLOL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
10 mg
Investigational Product Name
VERAPAMIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
480 mg
Investigational Product Name
METOPROLOL
Active Substance
METOPROLOL SUCCINATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
250 mg
Investigational Product Name
BISOPROLOL
Active Substance
BISOPROLOL FUMARATE, HYDROCHLOROTHIAZIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
10 mg
Investigational Product Name
FLECAINIDE
Active Substance
FLECAINIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
250 mg
Investigational Product Name
QUINIDINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
1200 mg
Combination Treatment
Yes

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