Ventricular TachycardiaPhase 2/3NCT04134845
A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias.
A Phase 2/3 study testing Dantrolene/Ryanodex in people with Ventricular Tachycardia, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventricular Tachycardia
- What is being tested?
- Dantrolene/Ryanodex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Aug 2020to 29 Aug 2025
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: A Randomized Controlled Trial of RyR2 Inhibition With Dantrolene and Susceptibility to Ventricular Arrhythmias in Patients With Structural Heart Disease.
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.
Read the 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 Ventricular Tachycardia/Ventricular Fibrillation (VT/VF). Dantrolene, a currently available drug that inhibits RyR2, but has no Sodium (Na) or potassium (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 Ventricular Tachycardia (VT) ablation.
Aim 2: To explore the pharmacokinetic/pharmacodynamic relationship of IV dantrolene and its short-term effect on cardiac electrophysiology, hemodynamics, and muscle and respiratory strength.
- Conditions
- Ventricular Tachycardia
- Being tested
- Dantrolene/Ryanodex, Placebo
- Keywords
- Ventricul Tachycardia ablation
- Medical subject headings
- Tachycardia, Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dantrolene/RyanodexDrug
Also called Dantrium, Ryanodex
muscle relaxant
PlaceboDrug
Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
| Study group | Role | What they receive |
|---|---|---|
| Dantrolene/Ryanodex | Experimental | Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Receives: Drug: Dantrolene/Ryanodex |
| Placebo | Placebo comparator | controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
A standardized induction protocol is performed using programmed ventricular stimulation from the Right Ventricular apex which was done pre-drug/placebo and post drug/placebo. The induction is single, double or triple extra beats of stimulation.
Measured: 10 minutes post drug infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start21 Aug 2020
- Primary completion29 May 2025
- Study completion29 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ventricular TachycardiaStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William Stevenson, Vanderbilt University Medical Center
- Investigators
- William Stevenson, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04134845
- Sponsor's protocol ID
- 190797
- Status last verified
- Sep 2026
- First submitted
- 10 Oct 2019
- Last updated
- 8 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40894163
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of RyR2 Inhibition With Dantrolene and Susceptibility to Ventricular Arrhythmias in Patients With Structural Heart Disease.
- ClinicalTrials.gov ID
- NCT04134845
- Acronym / sponsor ID
- 190797
- Conditions
- Ventricular Tachycardia
- Keywords
- Ventricul Tachycardia ablation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 21 Aug 2020 (actual)
- Primary completion
- 29 May 2025 (actual)
- Study completion
- 29 Aug 2025 (actual)
- First posted
- 22 Oct 2019 (actual)
- Results
- Posted 15 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 Ventricular Tachycardia/Ventricular Fibrillation (VT/VF). Dantrolene, a currently available drug that inhibits RyR2, but has no Sodium (Na) or potassium (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 Ventricular Tachycardia (VT) ablation.
Aim 2: To explore the pharmacokinetic/pharmacodynamic relationship of IV dantrolene and its short-term effect on cardiac electrophysiology, hemodynamics, and muscle and respiratory strength.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Dantrolene/Ryanodex | Experimental | Drug: Dantrolene/RyanodexDantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose |
| Placebo | Placebo comparator | Drug: Placebocontrolled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dantrolene/RyanodexAlso: Dantrium, Ryanodexmuscle relaxant | Drug | Dantrolene/Ryanodex |
| PlaceboControlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose | Drug | Placebo |
Primary outcome
Number of Participants With Inducible Sustained Ventricular Tachycardia/ Ventricular Fibrillation (VT/VF) Utilizing Standardized Stimulation Protocol.
Time frame: 10 minutes post drug infusion
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.
1 secondary outcome
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo.
Time frame: 10 minutes post drug infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40894163El-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.
- Individual participant dataSharing planned: No
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Assessment of Combined CCM and ICD Device in HFrEF
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A Study Assessing Arrhythmia Mapping With a Multi-Electrode Mapping Catheter
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Stevenson, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dantrolene/Ryanodex in people with Ventricular Tachycardia, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Inducible Sustained Ventricular Tachycardia/ Ventricular Fibrillation (VT/VF) Utilizing Standardized Stimulation Protocol. (time frame: 10 minutes post drug infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04134845, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.