The QUEEN-IVF trial: Quinidine versus verapamil in short-coupled idiopathic ventricular fibrillation: An open-label, randomized crossover pilot trial

Overview

Sponsor-declared trial summary

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

25 Nov 2024 → ongoing

Decision date (initial)

2024-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-511190-30-00

EudraCT number

2021-005688-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The objective of this study is to determine the advisability and feasibility of a definitive RCT that will assess quinidine as compared with verapamil in patients with short-coupled IVF in terms of the safety and efficacy with regard to arrhythmic events.

Conditions and MedDRA coding

Short-coupled Idiopathic Ventricular Fibrillation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. Functioning transvenous or subcutaneous ICD in place
3. Sudden cardiac arrest, (near)syncope, appropriate ICD shock or nonsustained PVT documented by the ICD at least once in the past 2 years
4. 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
5. Willing to undergo two assigned treatment periods with verapamil and quinidine
6. Age ≥ 18 years

Exclusion criteria 20

1. Pregnancy or lactation
2. 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
3. Patients with a history of therapy refractory ventricular arrhythmia on an adequate dose of verapamil or quinidine, as determined by the treating cardiologist.
4. Contra-indication to quinidine or verapamil (see section 7.6)
5. 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)
6. Suspicion or definitive diagnosis of another (heritable) arrhythmia syndrome, e.g. Brugada syndrome, early repolarization syndrome or catecholaminergic polymorphic ventricular tachycardia
7. Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT interval on the resting ECG at baseline
8. Presence of a pathogenic or likely-pathogenic ryanodine receptor 2 (RYR2) mutation
9. Presence of ischemia-induced short-coupled ventricular arrhythmia in patient with documented coronary spasm
10. 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
11. 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)
12. Reversible metabolic or pharmacological/toxicological conditions that may cause electrophysiological findings similar to short-coupled IVF
13. 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
14. 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
15. Intention to perform radiofrequency ablation of the PVC initiating short-coupled IVF during the course of the study
16. Serious known comorbid disease with a life expectancy of less than two years
17. 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
18. Circumstances that prevent follow-up
19. Inability to take orally administered tablets
20. Inability to provide informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is sustained ventricular arrhythmia, assessed using the severity scoring system. A subject will be scored in each treatment period according to the scoring system by the ECC. The highest applicable score will be used

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

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

Christian van der Werf

Public contact point

Organisation

Amsterdam UMC

Contact name

Christian van der Werf

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications