A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias.

NCT04134845 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 190797
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Ventricular Tachycardia

Keywords

Ventricul Tachycardia ablation

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Inducible Sustained Ventricular Tachycardia/ Ventricular Fibrillation (VT/VF) Utilizing Standardized Stimulation Protocol.

  Post drug ventricular stimulation with Right Ventricle (RV) ventricular catheter in the Right Ventricle( RV) apex with increasing extra stimuli with planned decrement stimuli by 10 milliseconds (ms) to effective refractory period (ERP). Outcome is measured as Ventricular inducibility yes/no.

  10 minutes post drug infusion

Secondary Outcomes (1)

• Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo.

  10 minutes post drug infusion

Other Outcomes (25)

• Serial Heart Rate Measurements

  pre drug infusion, 1 minute, 5 minute, 10 minute and 20 minutes post infusion

• Number of Participants With a Change of Blood Pressure

  1 minute, 5 minute,10 minute, 15 minute and 20 minutes post infusion.

• Serial Arterial O2 Sats

  pre drug, post drug 1 minute, 5 minute, 10 minute and 20 minutes

Study Arms (2)

Dantrolene/Ryanodex

EXPERIMENTAL

Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose

Drug: Dantrolene/Ryanodex

Placebo

PLACEBO COMPARATOR

controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose

Drug: Placebo

Interventions

Placebo DRUG

Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose

Placebo

Dantrolene/Ryanodex DRUG

muscle relaxant

Also known as: Dantrium, Ryanodex

Dantrolene/Ryanodex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• El-Harasis MA, Yoneda ZT, Varghese B, Grauherr D, Crawford DM, Schmeckpeper J, Williams HL, Ye F, Sun L, Tandri H, Richardson T, Kanagasundram A, Davogustto G, Roden D, Mantinan M, Pretorius M, Billings FT, Siegrist K, Akers WS, Stevenson WG, Knollmann BC, Shoemaker MB. Ryanodine Receptor Inhibition with Dantrolene Prevents Ventricular Tachycardia Induction in Patients with Structural Heart Disease - A Randomized Controlled Trial. medRxiv [Preprint]. 2025 Aug 19:2025.08.17.25333868. doi: 10.1101/2025.08.17.25333868.

  PMID: 40894163 DERIVED

MeSH Terms

Conditions

Tachycardia, Ventricular

Interventions

Dantrolene

Condition Hierarchy (Ancestors)

Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. William Stevenson
• Organization: Vanderbilt University Medical Center

William.g.stevenson@vumc.org

615-322-2318

Study Officials

• William Stevenson, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: 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

Study Record Dates

• First Submitted: October 10, 2019
• First Posted: October 22, 2019
• Study Start: August 21, 2020
• Primary Completion: May 29, 2025
• Study Completion: August 29, 2025
• Last Updated: March 10, 2026
• Results First Posted: August 15, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)