A Randomized Crossover Pilot Study of Quinidine Versus Verapamil in Patients with Short-Coupled Idiopathic Ventricular Fibrillation
- Trial ID
- 2024-511190-30-00
- Sponsor
- Amsterdam UMC Stichting
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the QUEEN-IVF trial is to evaluate the advisability and feasibility of conducting a definitive randomized controlled trial (RCT) to compare **quinidine** with **verapamil** in patients diagnosed with short-coupled **Idiopathic Ventricular Fibrillation** (IVF). This study aims to assess the safety and efficacy of these treatments concerning arrhythmic events. The clinical relevance of this objective lies in determining the most effective therapeutic approach for managing arrhythmic events in this patient population, potentially improving patient outcomes and guiding future treatment protocols.
Participants
The clinical trial involves participants diagnosed with **Short-coupled Idiopathic Ventricular Fibrillation**. The study population includes both male and female subjects aged 18 years and older. The trial does not involve a vulnerable population. Participants were selected based on specific diagnostic criteria, including documentation of polymorphic ventricular tachycardia or ventricular fibrillation initiated by a premature ventricular contraction with a coupling interval of less than 350 milliseconds. Additionally, participants must have a functioning transvenous or subcutaneous implantable cardioverter-defibrillator and have experienced sudden cardiac arrest, syncope, or appropriate ICD shock within the past two years. Genetic testing is initiated for participants, although results are not required at the time of inclusion. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified. The trial aims to assess the safety and efficacy of quinidine compared to verapamil in managing arrhythmic events in this patient population.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and **efficacy** of quinidine compared to verapamil in patients with short-coupled idiopathic ventricular fibrillation. This study is structured as an open-label, randomized crossover pilot trial, with a primary focus on assessing sustained ventricular arrhythmia using a severity scoring system. The trial is expected to span from October 2022 to September 2027, with participant involvement lasting up to 18 months. The trial will include a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific diagnostic criteria, such as the presence of a functioning ICD and a history of sudden cardiac arrest or arrhythmogenic syncope.
Participants will undergo two treatment periods, each involving the administration of either verapamil or quinidine, with the sequence of treatments being randomized. The study will include follow-up visits to monitor the occurrence of arrhythmic events and to ensure participant safety. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary endpoint. Participants may be withdrawn from the study if they experience adverse events that compromise their safety or if they fail to comply with the study protocol. The trial's design ensures that all participants receive both treatments, allowing for a comprehensive comparison of the two medications' effects on the targeted condition.
Treatment
The clinical trial involves the administration of **VERAPAMIL**, a chemical compound classified under the ATC code C08DA01. The pharmaceutical form of VERAPAMIL is denoted as PHF00209MIG, and it is administered orally. The maximum daily dose is set at 480 mg, with a total maximum dose of 262,800 mg over the course of the study. The treatment period is limited to 18 months. VERAPAMIL is utilized as a test medication in this trial, and its administration is monitored to ensure participant compliance with the dosing schedule.
**QUINIDINE** is employed as a comparator treatment in this study, classified under the ATC code C01BA01. Similar to VERAPAMIL, QUINIDINE is administered in the pharmaceutical form PHF00209MIG and is taken orally. The maximum daily dose for QUINIDINE is 1200 mg, with a total maximum dose of 657,000 mg over the 18-month treatment period. The study aims to evaluate the safety and efficacy of QUINIDINE in comparison to VERAPAMIL, focusing on arrhythmic events in patients with short-coupled idiopathic ventricular fibrillation. Compliance with the dosing regimen is closely monitored throughout the trial.
Efficacy
Efficacy in the clinical trial titled "The QUEEN-IVF trial: Quinidine versus verapamil in short-coupled idiopathic ventricular fibrillation" will be assessed primarily through the evaluation of sustained ventricular arrhythmia. This will be measured using a severity scoring system, with each subject being scored in each treatment period according to the system established by the ECC. The highest applicable score during the treatment period will be utilized to determine efficacy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- At least one of the following 3 principal diagnostic criteria for short-coupled IVF: A. Diagnosis of short-coupled IVF, based on any documentation (i.e., ECG, Holter monitor, device electrogram (EGM), or telemetry) of PVT of ≥3 consecutive beats or VF initiated by a PVC with a coupling interval <350 ms B. Isolated PVCs with a coupling interval <350 ms during the index admission after SCA based on a shockable rhythm or (presumed) arrhythmogenic syncope C. DPP6 haplotype carrier
- Functioning transvenous or subcutaneous ICD in place
- Sudden cardiac arrest, (near)syncope, appropriate ICD shock or nonsustained PVT documented by the ICD at least once in the past 2 years
- Genetic testing has been initiated. Results are not required to be known at the time of inclusion. In subjects who are family members of DPP6 carrying index patients, genes other than DPP6 are not required to be tested
- Willing to undergo two assigned treatment periods with verapamil and quinidine
- Age ≥ 18 years
Exclusion Criteria
- Pregnancy or lactation
- Current treatment with class 1 antiarrhythmic medication (other than quinidine), class 3 antiarrhythmic medication, or digoxin, unless this medication is discontinued; patients who are currently treated with amiodarone will not be included due to the long elimination half-life of amiodarone, unless amiodarone was only administered intravenously for a short period of time
- Patients with a history of therapy refractory ventricular arrhythmia on an adequate dose of verapamil or quinidine, as determined by the treating cardiologist.
- Contra-indication to quinidine or verapamil (see section 7.6)
- Significant structural heart disease (left ventricular ejection fraction <50%, suspicion or definitive diagnosis of cardiomyopathy, moderate/severe pulmonary, mitral, or aortic valve stenosis or 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
- Presence of a pathogenic or likely-pathogenic ryanodine receptor 2 (RYR2) mutation
- Presence of ischemia-induced short-coupled ventricular arrhythmia in patient with documented coronary spasm
- Presence of pause-dependent torsade de pointes [preceding R–R interval prior to the trigger PVC >1500 ms in individuals without pacemaker/ICD or >1300 ms in individuals with pacemaker/ICD] following a stable baseline rhythm. Initiation of ventricular arrhythmia by short-long-short cycles (R–R cycles <1300 ms) with a shortcoupled trigger PVC is allowed
- Significant coronary artery disease (≥50% narrowing of the diameter of the lumen of the left main coronary artery or ≥70% narrowing of the diameter of the lumen of the left anterior descending coronary artery, left circumflex artery or right coronary artery)
- Reversible metabolic or pharmacological/toxicological conditions that may cause electrophysiological findings similar to short-coupled IVF
- Patients who are considered electrically unstable, at physician’s discretion, due to active electrical storm or very frequent nonsustained episodes of short-coupled IVF requiring intravenous or invasive therapy
- Successful radiofrequency ablation of the PVC initiating short-coupled IVF and absence of documented (non)sustained episodes of short-coupled PVT/VF afterwards. The patient will, however, be eligible to participate in the study if ≥ 1 episode of short-coupled PVT/VF is documented after the ablation procedure
- Intention to perform radiofrequency ablation of the PVC initiating short-coupled IVF during the course of the study
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 01 Oct 2022 | — |
| Netherlands | — | — | 24 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VERAPAMIL | Test | PHF00209MIG | ORAL | 480 | 18 | SCP1068778 |
QUINIDINE | Comparator | PHF00209MIG | ORAL | 1200 | 18 | SCP189696 |