Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Authorised, recruiting
Participants planned
10
Countries
1
Sites
1
Andersen-Tawil syndrome
The objective of this study is to investigate the efficacy of flecainide monotherapy as compared with combination therapy of flecainide and beta-blockers or calcium channel blockers in patients with ATS and MEPPC. For MEPPC patients, quinidine will be compared with flecainide monotherapy in phase 2.
Key facts
- Sponsor
- Amsterdam UMC
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 13 Aug 2025 → ongoing
- Decision date (initial)
- 2024-06-10
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-510682-42-01
- WHO UTN
- U1111-1302-8267
- ClinicalTrials.gov
- NCT06205550
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
The objective of this study is to investigate the efficacy of flecainide monotherapy as compared with combination therapy of flecainide and beta-blockers or calcium channel blockers in patients with ATS and MEPPC.
For MEPPC patients, quinidine will be compared with flecainide monotherapy in phase 2.
Conditions and MedDRA coding
Andersen-Tawil syndrome
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-510682-42-00 | Optimal drug therapy for the suppression of ventricular arrhythmias in Andersen-Tawil syndrome and multifocal ectopic Purkinje-related premature contractions: a series of N-of-1 trials | Amsterdam UMC |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- One of the following two primary diagnostic criteria A. Clinical diagnosis of ATS. Genetically confirmed diagnosis (i.e. class 4 or 5 KCNJ2 variant) is not required B. Clinical diagnosis of MEPPC and carrier of associated class 4 or 5 SCN5A variant
- 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)
- Is currently treated with a stable (at least 3 months) dose of flecainide
- Age ≥ 18 years
Exclusion criteria 11
- Pregnancy
- Contra-indication to study medication
- 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)
- Suspicion or definitive diagnosis of another (heritable) arrhythmia syndrome, e.g. Brugada syndrome, early repolarization syndrome or catecholaminergic polymorphic ventricular tachycardia
- Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT interval on the resting ECG at baseline
- History of therapy refractory ventricular arrhythmia or intolerable side-effects on an adequate dose of any study medication, as determined by the treating cardiologist
- Serious known comorbid disease with a life expectancy of less than two years
- 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
- Circumstances that prevent follow-up
- Inability to take orally administered tablets
- Inability to provide informed consent
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The ventricular ectopy burden per 24-hour period.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 8
—
SCP1068778 · ATC
- Route of administration
- ORAL
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 16800 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C08DA01 — VERAPAMIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
—
SCP189696 · ATC
- Route of administration
- ORAL
- Max daily dose
- 1200 mg milligram(s)
- Max total dose
- 42000 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C01BA01 — QUINIDINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1160479 · ATC
- Active substance
- Atenolol
- Substance synonyms
- 2-[4-[2-HYDROXY-3-(PROPAN-2-YLAMINO)PROPOXY]PHENYL]ACETAMIDE
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 3500 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C07AB03 — ATENOLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1126442 · ATC
- Active substance
- Bisoprolol Fumarate
- Substance synonyms
- BUT-2-ENEDIOIC ACID: 1-(PROPAN-2-YLAMINO)-3-[4-(2-PROPAN-2-YLOXYETHOXYMETHYL)PHENOXY]PROPAN-2-OL
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 350 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C07AB07 — BISOPROLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1159601 · ATC
- Active substance
- Metoprolol Succinate
- Substance synonyms
- BUTANEDIOIC ACID, 1-[4-(2-METHOXYETHYL)PHENOXY]-3-(PROPAN-2-YLAMINO)PROPAN-2-OL
- Route of administration
- ORAL
- Max daily dose
- 250 mg milligram(s)
- Max total dose
- 8750 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C07AB02 — METOPROLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP129860 · ATC
- Active substance
- Propranolol Hydrochloride
- Substance synonyms
- PROPRANOLOLI HYDROCHLORIDUM, PROPRANOLOL HYDROCHLORIIDE, 1-NAPHTHALEN-1-YLOXY-3-(PROPAN-2-YLAMINO)PROPAN-2-OL HYDROCHLORIDE
- Route of administration
- ORAL
- Max daily dose
- 160 mg milligram(s)
- Max total dose
- 5600 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C07AA05 — PROPRANOLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP13264491 · ATC
- Active substance
- Flecainide
- Route of administration
- ORAL
- Max daily dose
- 250 mg milligram(s)
- Max total dose
- 17500 mg milligram(s)
- Max treatment duration
- 10 Week(s)
- Authorisation status
- Authorised
- ATC code
- C01BC04 — FLECAINIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1150567 · ATC
- Active substance
- Nebivolol
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 350 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- C07AB12 — NEBIVOLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Amsterdam UMC
- Sponsor organisation
- Amsterdam UMC
- Address
- De Boelelaan 1117
- City
- Amsterdam
- Postcode
- 1081 HV
- Country
- Netherlands
Scientific contact point
- Organisation
- Amsterdam UMC
- Contact name
- dr. C. van der Werf
Public contact point
- Organisation
- Amsterdam UMC
- Contact name
- dr. C. van der Werf
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Authorised, recruiting | 10 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Amsterdam UMC
Cardiology, De Boelelaan 1117, 1081 HV, Amsterdam
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 |
|---|---|---|---|---|---|
| Netherlands | 2025-08-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-510682-42-01 | 1.2 |
| Protocol (for publication) | D1_Protocol 2024-510682-42-01_SoC | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC atenolol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC bisoprolol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC flecainide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC metoprolol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC nebivolol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC propranolol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC quinidine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC verapamil | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis dutch 2024-510682-42-01 | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-04 | Netherlands | Acceptable with conditions 2024-06-03
|
2024-06-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-06-27 | Netherlands | Acceptable 2024-07-12
|
2024-07-12 |