A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias.

Phase 2

Active, not recruiting

• Conditions: Ventricular Tachycardia
• Interventions: Drug: Dantrolene/Ryanodex; Drug: Placebo

• Registration Number: NCT04134845
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

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.

Detailed Description

The hypothesis to be tested is that RyR2 hyperactivity in patients with structural heart disease drives proarrhythmic changes in refractoriness and conduction, and decreases cardiac contractility, which promotes VT/VF. Dantrolene, a currently available drug that inhibits RyR2, but has no Na or K channel activity, will be used as a tool to study RyR2 modulation. The investigators propose a randomized controlled trial of dantrolene versus placebo in patients with structural heart disease referred for VT ablation to evaluate electrophysiologic, hemodynamic, and arrhythmia prevention endpoints. Dantrolene's inhibition of RyR1 will also be studied to define its effect on muscle and respiratory strength in this clinical population, which will be important if dantrolene is to be considered for repurposing as an antiarrhythmic drug.

The two aims are:

Aim 1: To conduct a randomized, placebo-controlled trial of dantrolene to study the effect of RyR inhibition on cardiac electrophysiology, hemodynamics, arrhythmia inducibility, muscle strength, and respiratory mechanics in patients with structural heart disease referred for VT ablation.

Aim 2: To explore the pharmacokinetic/pharmacodynamic relationship of I.V. dantrolene and its short-term effect on cardiac electrophysiology, hemodynamics, and muscle and respiratory strength.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-10-10
• Study First Submitted QC: 2019-10-18
• Study First Posted: 2019-10-22
• Study Start: 2020-08-21
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-18
• Primary Completion: 2025-03
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dantrolene/Ryanodex	Dantrolene/Ryanodex	Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose
Placebo	Placebo	controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose

Primary Outcome Measures

Name	Time	Method
Inducibility of sustained VT/VF by standardized ventricular stimulation protocol	10 minutes post drug infusion	Post drug ventricular stimulation with RV ventricular catheter in the RV apex with increasing extra stimuli with planned decrement stimuli by 10 ms to ERP. Outcome is measured as Ventricular inducibility yes/no.

Secondary Outcome Measures

Name	Time	Method
Stage of inducibility by standardized ventricular stimulation protocol of the sustained VT/VF	10 minutes post drug infusion	measured as ordinal variable for stage of ventricular stimulation protocol;specific step by step V-stim research protocol will be followed with single extra stimuli up to six extra stimuli added to VERP. What stage of Inducible VT will be recorded.

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States