A Randomized Controlled Trial of RyR2 Inhibition With Dantrolene and Susceptibility to Ventricular Arrhythmias in Patients With Structural Heart Disease.

190797

This is a randomized, placebo controlled trial of Dantrolene (N= 84 participants) to demonstrate the feasibility of using I.V. dantrolene to study the effect of RyR2 inhibition on cardiac electrophysiology, hemodynamics and ventricular arrhythmia inducibility in patients with structural heart disease referred for VT ablation. The investigators will also explore the pharmacokinetic/pharmacodynamic relationship of I.V. dantrolene and it short-term effect on specific cardiac electrophysiologic and hemodynamic parameters.

2020-08-21

2024-06-01

2024-06-01

Active (not recruiting)

Early phase I

84

Inclusion Criteria: * Greater than or equal to 18 years of age * Able to give written informed consent * Referred for catheter-based VT ablation * Structural heart disease (cardiomyopathy or RV/LV scar) * Permanent pacemaker or implantable cardioverter defibrillator Exclusion Criteria: * Mechanical ventricular support (e.g. LVAD, ECMO) * NYHA class IV heart failure * LVEF \< 20% * Morbid obesity (BMI \> 40 kg/m2) * Severe renal insufficiency (GFR\<30 mL/min) * Chronic liver disease (Child Pugh class A-C) * Current use of calcium channel blockers * Neuromuscular disorder (e.g. muscular dystrophy) * Chronic obstructive pulmonary disease or restrictive lung disease requiring oxygen * Therapy or history of intubation * Pregnant or nursing * History of dysphagia

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '84 participants will be randomly assigned in a 2:1 ratio to treatment (dantrolene) or control (placebo). A computer-generated randomization list will be prepared by the study statistician using the stratified permuted block randomization, where block size varies randomly from 4 or 6 to ensure overall balance across treatment arms. Randomization will be stratified by 1) documented CAD with prior infarct, 2) amiodarone use within the past 21 days defined as chronic oral use or \\>5 grams cumulative, 3) LVEF \\<35%. Enrollment will be evenly distributed across the two study arms by the stratification factors', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': "The study statistician will generate the allocation schedule but will remain blinded to the treatment assignment as well as the study staff physician's. The research clinician will not be blinded.", 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 84, 'type': 'ESTIMATED'}}

2024-02-15