Dantrolene for Ventricular Arrhythmias

Overseen By Ben M Shoemaker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vanderbilt University Medical Center

Must not be taking: Calcium channel blockers

Disqualifiers: Mechanical support, NYHA IV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Dantrolene, administered through an IV, to determine its effectiveness in managing heart rhythm problems in individuals with certain heart conditions. The primary focus is on those with structural heart disease undergoing treatment for Ventricular Tachycardia, a type of irregular heartbeat. Participants will receive either Dantrolene or a placebo to compare effects. This study suits individuals with a pacemaker or defibrillator who are scheduled for a specific heart procedure. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group.

Do I need to stop taking my current medications for the trial?

The trial requires that you do not use calcium channel blockers. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dantrolene, the treatment under study in this trial, is generally safe for people. A previous study found that dantrolene reduced the risk of ventricular tachycardia, a fast heart rhythm, in high-risk patients, with most experiencing no significant side effects.

Another study demonstrated positive results regarding the safety of RYANODEX® (a form of dantrolene) in patients with heart issues, suggesting the treatment is likely safe for most people. While more research is needed, current evidence supports its use with a good safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ventricular arrhythmias, which typically include medications like beta-blockers and antiarrhythmic drugs, Dantrolene/Ryanodex offers a novel approach by targeting the ryanodine receptor. This receptor plays a crucial role in calcium regulation within heart cells, and Dantrolene/Ryanodex works to stabilize its function, potentially reducing abnormal heart rhythms. Researchers are excited about this treatment because it offers a unique mechanism of action that could be more effective in cases where traditional therapies fall short. Additionally, its rapid intravenous administration could provide quick relief during acute episodes.

What evidence suggests that Dantrolene might be an effective treatment for ventricular arrhythmias?

In this trial, participants will receive either Dantrolene/Ryanodex or a placebo. Research has shown that dantrolene can significantly reduce the risk of ventricular tachycardia (VT), a type of irregular heartbeat. One study found that dantrolene lowered the occurrence of VT by 66%, while the placebo had no effect. This suggests that dantrolene might help manage abnormal heart rhythms by affecting a protein involved in heart muscle contraction. Additionally, animal studies found that dantrolene improved survival rates and reduced irregular heart signals. These findings indicate that dantrolene holds promising potential for treating heart rhythm problems in humans. ^{3 6 7 8 9}

Who Is on the Research Team?

William Stevenson, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with a rapid heartbeat condition called ventricular tachycardia, who are referred for VT ablation and have structural heart disease. They must be able to consent and not have severe heart failure, morbid obesity, major kidney or liver issues, neuromuscular disorders, severe lung disease requiring oxygen, or be on certain medications like calcium channel blockers.

Inclusion Criteria

I have a heart condition involving the heart muscle or scarring.

You have a permanent pacemaker or implantable cardioverter defibrillator.

I have a heart condition involving the heart muscle or scarring.

Exclusion Criteria

Pregnant or nursing

I am currently taking calcium channel blockers.

I have been intubated or am currently on a breathing machine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intravenous administration of Dantrolene or placebo to study the effect on cardiac electrophysiology and hemodynamics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including various physiological measurements

2-4 hours post-procedure

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dantrolene/Ryanodex
• Placebo

Trial Overview The study tests if Dantrolene can affect cardiac electrophysiology and reduce the inducibility of ventricular arrhythmias in patients with heart structure problems. It's a randomized trial where half the participants will receive Dantrolene while the other half will get a placebo.

How Is the Trial Designed?

Group I: Dantrolene/Ryanodex Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Cardiac safety pharmacology is crucial for assessing the risk of potentially lethal heart-related side effects from new drugs, particularly focusing on the risk of torsades de pointes (TdP) linked to changes in the QT interval on ECG.

The current paradigm for cardiac safety assessment, guided by ICH S7A and S7B, emphasizes the use of advanced non-clinical models and methods, including in vitro assays and biomarkers, to predict and monitor cardiac risks associated with new chemical entities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysics and Molecular Biology of Cardiac Ion Channels for the Safety Pharmacologist. Pugsley, MK., Curtis, MJ., Hayes, ES.[2015]

A comprehensive database of 396,985 drug-related cardiac adverse effects (AEs) linked to 1,632 approved drugs was created, revealing significant clusters of AEs affecting heart function, such as arrhythmias and heart failure.

The study identified that cardiac AEs are highly correlated with drugs targeting cardiovascular functions and specific mechanisms of action, including interactions with various receptors like alpha- and beta-adrenergic receptors, which may help predict and understand these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence. Matthews, EJ., Frid, AA.[2013]

The review highlights the importance of assessing the cardiac safety profile of antiemetic drugs, particularly 5HT3 receptor antagonists, used in cancer patients to prevent chemotherapy-induced nausea and vomiting.

Most antiemetic drugs were approved before the implementation of ICHE14 guidelines, meaning their cardiotoxicity was primarily evaluated through post-marketing surveillance rather than controlled studies, indicating a need for ongoing monitoring of their cardiac effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of antiemetic drugs in oncology: An overview of the current state of the art. Barni, S., Petrelli, F., Cabiddu, M.[2022]

Citations

1. medrxiv.org medrxiv.org/content/10.1101/2025.08.17.25333868v1

Ryanodine Receptor Inhibition with Dantrolene Prevents ... Dantrolene reduced inducible VT by 66% whereas placebo had no effect (odds ratio 0.23, 95% CI 0.06-0.90, P=0.034). Dantrolene had no significant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04134845

NCT04134845 | A Clinical Trial Utilizing Dantrolene in ... A Randomized Controlled Trial of RyR2 Inhibition With Dantrolene and Susceptibility to Ventricular Arrhythmias in Patients With Structural Heart Disease.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8183840/

Chronic dantrolene treatment attenuates cardiac dysfunction ... Dantrolene treatment has been shown to improve survival after ventricular fibrillation in a pig model and suppress spontaneous focal discharge in an ovine ...

4. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)02095-8/fulltext

PO-CES-06 RYANODINE RECEPTOR-2 (RYR2) ... Dantrolene reduced inducible VT from 41% to 14% vs. 46% to 41% in the placebo group (odds ratio 0.23, 95% CI 0.06-0.90, P=0.034). Dantrolene did not alter ...

5. journal-of-cardiology.com journal-of-cardiology.com/article/S0914-5087(19)30282-5/fulltext

A multicenter, randomized, double-blind, controlled study ... The results of this trial will clarify the efficacy and safety of dantrolene for ventricular arrhythmia, as well as mortality and morbidity ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40894163/

Ryanodine Receptor Inhibition with Dantrolene Prevents ... We conclude that Dantrolene reduced VT inducibility in high-risk patients with a favorable safety profile.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0914508719302825

A multicenter, randomized, double-blind, controlled study ... The results of this trial will clarify the efficacy and safety of dantrolene for ventricular arrhythmia, as well as mortality and morbidity in patients with ...

8. investor.eagleus.com investor.eagleus.com/news-releases/news-release-details/eagle-pharmaceuticals-reports-successful-outcomes-safety-and

News Details Positive results from a recently-completed study evaluating the safety and efficacy of RYANODEX® (dantrolene sodium for injectable suspension) for the ...

9. jacc.org jacc.org/doi/10.1016/j.jacep.2018.08.001

Safety of Chronic Cardiac Ryanodine Receptor Modulation Furthermore, dantrolene enhanced cardiac function in failing hearts (5) and improved short-term survival in ventricular arrhythmia (2). However, much needed ...