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NCT Number: NCT06205550

N-of-1 in ATS and MEPPC

Rationale: Andersen-Tawil syndrome (ATS) is a very rare heritable cardiac arrhythmia syndrome that is characterized by the triad of periodic paralysis, physical dysmorphisms, and ventricular arrhythmias, including bidirectional ventricular tachycardia (VT), polymorphic VT, and frequent multifocal premature ventricular contractions (PVCs). Multifocal ectopic Purkinje-related premature contractions (MEPPC) is a very rare syndrome characterized by frequent multifocal PVCs with relatively narrow QRS width. In both conditions, patients most often present with palpitations, but syncope and sudden cardiac arrest have also been reported. Left untreated, the large burden of PVCs can lead to PVC-induced cardiomyopathy. A number of therapeutic strategies are suggested in these conditions, but there is a lack of high-quality evidence on their efficacy.

Objective: To investigate the efficacy of various therapeutic strategies for reducing ventricular ectopy burden in patients with ATS or MEPPC.

Study design: Aggregated series of randomized, open-label N-of-1 trials. Each N-of-1 trial will consist of at least 2 treatment sets, each of which comprise two 7-day periods of treatment with therapy A and B, in a semi-randomized, counterbalanced order.

Study population: Adult patients with ATS or MEPPC on flecainide therapy.

Intervention: For ATS, flecainide monotherapy will be compared with combination therapy of flecainide and a β-blocker or calcium channel blocker. For MEPPC, flecainide monotherapy will be compared with combination therapy of flecainide and a β-blocker or calcium channel blocker (phase 1), and flecainide will be compared with quinidine (phase 2).

Main study endpoint: Ventricular ectopy burden on electrocardiographic monitoring.

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Key information

Conditions

Andersen Tawil Syndrome Andersen Syndrome Arrhythmias, Cardiac Cardiac Conduction System Disease Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Heart Defects, Congenital Heart Diseases Long QT Syndrome Multifocal Ectopic Purkinje-related Premature Contractions Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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 flecainide
  • Age ≥ 18 years

Exclusion criteria

  • Pregnancy
  • Contra-indication to study medication (see section 7.4)
  • 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

Treatment and study plan

Flecainide

Drug

Flecainide monotherapy

Flecainide + beta-blocker

Drug

Flecainide + beta-blocker

Primary outcomes

  1. Ventricular ectopy burden

    Time frame: 5 24-hour periods per treatment period

Secondary outcomes

  1. Duration of longest ventricular tachycardia

    Time frame: 5 24-hour periods per treatment period

Study contacts

Contact information is provided by the study sponsor or research team.

Christian van der Werf, MD PhD

CONTACT

[email protected]

+31 020 566 9111

Sponsors and collaborators

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2025
Study completion
2025
First posted
Jan 16, 2024
Registry last updated
Jan 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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