Trial Outcomes & Findings for A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias. (NCT NCT04134845)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

68 participants

Primary outcome timeframe

10 minutes post drug infusion

Results posted on

2025-10-28

Participant Flow

A member of the study team identified eligible subjects. Eligible subjects were identified if they were scheduled for a Ventricular Tachycardia (VT) ablation or a Premature Ventricular Contraction (PVC) ablation. The study coordinator then requested permission to contact them about research. If the patient agreed, a member of the study team would approach the patient in person in the Arrhythmia Clinic, Vanderbilt University Hospital, or by phone before ablation.

Sixty-eight subjects were enrolled. Fifty-one completed the protocol. 17 participants didn't receive either the drug or the placebo and were withdrawn. Nine due to a prolonged procedure, one developed hypotension, two had tachycardia, one had pulmonary concerns from anesthesia, one participant's eGFR was low, one had a drop in venous oxygen during procedure, one had safety concerns due to several cardioversion's during the procedure and one had a drop in ejection fraction.

Participant milestones

Participant milestones
Measure	Dantrolene/Ryanodex Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
Overall Study STARTED	41	27
Overall Study COMPLETED	29	22
Overall Study NOT COMPLETED	12	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Dantrolene/Ryanodex Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
Overall Study withdrawl by PI	12	5

Baseline Characteristics

17 participants did not receive either the drug or the placebo and were withdrawn from the RCT. Nine due to a prolonged procedure, one developed hypotension, two had tachycardia, one had pulmonary concerns from anesthesia, one participant's eGFR was low, one had a drop in venous oxygen during procedure, one had safety concerns due to several cardioversion's during the procedure and one had a drop in ejection fraction.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dantrolene/Ryanodex n=29 Participants Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo n=22 Participants controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose	Total n=51 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	15 Participants n=7 Participants	34 Participants n=5 Participants
Age, Continuous	68.2 years n=5 Participants	67.0 years n=7 Participants	67.8 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	21 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	20 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants • 17 participants did not receive either the drug or the placebo and were withdrawn from the RCT. Nine due to a prolonged procedure, one developed hypotension, two had tachycardia, one had pulmonary concerns from anesthesia, one participant's eGFR was low, one had a drop in venous oxygen during procedure, one had safety concerns due to several cardioversion's during the procedure and one had a drop in ejection fraction.	22 participants n=7 Participants • 17 participants did not receive either the drug or the placebo and were withdrawn from the RCT. Nine due to a prolonged procedure, one developed hypotension, two had tachycardia, one had pulmonary concerns from anesthesia, one participant's eGFR was low, one had a drop in venous oxygen during procedure, one had safety concerns due to several cardioversion's during the procedure and one had a drop in ejection fraction.	51 participants n=5 Participants • 17 participants did not receive either the drug or the placebo and were withdrawn from the RCT. Nine due to a prolonged procedure, one developed hypotension, two had tachycardia, one had pulmonary concerns from anesthesia, one participant's eGFR was low, one had a drop in venous oxygen during procedure, one had safety concerns due to several cardioversion's during the procedure and one had a drop in ejection fraction.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dantrolene/Ryanodex n=29 Participants Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo n=22 Participants controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
Number of Participants With Inducible Sustained Ventricular Tachycardia/ Ventricular Fibrillation (VT/VF) Utilizing Standardized Stimulation Protocol.	4 Participants	9 Participants

SECONDARY outcome

Timeframe: 10 minutes post drug infusion

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.

Outcome measures

Outcome measures
Measure	Dantrolene/Ryanodex n=29 Participants Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo n=22 Participants controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo. Single extra beats/ pre drug/placebo	0 Participants	1 Participants
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo. Triple extra beats/pre drug/placebo	10 Participants	5 Participants
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo. Triple extra beats/post drug/placebo	3 Participants	5 Participants
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo. Single extra beats/post drug/placebo	0 Participants	1 Participants
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo. Double extra beats/pre drug/placebo	2 Participants	4 Participants
Stage of Inducibility of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) by Standardized Ventricular Stimulation Protocol Pre and Post Drug/Placebo. Double extra beats/post drug/placebo	1 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

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

Heart rate measurement performed by standard heart rate monitors in the Electrophysiology lab.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

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

Change in serial blood pressure at specified time points.

Outcome measures

Outcome measures
Measure	Dantrolene/Ryanodex n=29 Participants Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo n=22 Participants controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
Number of Participants With a Change of Blood Pressure 1 minute	0 Participants	0 Participants
Number of Participants With a Change of Blood Pressure 5 minutes	0 Participants	0 Participants
Number of Participants With a Change of Blood Pressure 10 minutes	0 Participants	0 Participants
Number of Participants With a Change of Blood Pressure 15 minutes	0 Participants	0 Participants
Number of Participants With a Change of Blood Pressure 20 minutes	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

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

Hemodynamic monitoring for O2 sats will be performed during ablation with an arterial line and pulmonary artery (PA) catheter (aka. Swann-Ganz Catheter).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

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

Hemodynamic monitoring for mixed venous O2 sats will be performed during ablation with an arterial line and pulmonary artery (PA) catheter (aka. Swann-Ganz Catheter).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

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

PA- mmHg; Hemodynamic monitoring for PA will be performed during ablation with an arterial line and pulmonary artery (PA) catheter (aka. Swann-Ganz Catheter).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

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

Measuring the Pulmonary Capillary Wedge pressure by the hemodynamic pulmonary cathether

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: post drug infusion at 5 minutes,10 minutes,15 minutes, 20 minutes, 1-4 hours, 6-12 hours,16-24 hours and optional 28-36 hours

The pharmacokinetic measurement of the time it takes for the concentration of the drug in the body to decrease by half.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Post drug infusion at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 1-4 hours, 6-12 hours,16-24 hours and optional 28-36 hours

A pharmacokinetic measure to determine the highest concentration of the drug.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Post drug infusion at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 1-4 hours, 6-12 hours,16-24 hours and optional 28-36 hours

Tmax (h) Time to maximum concentration by plasma concentration.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: post drug infusion at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 1-4 hours, 6-12 hours,16-24 hours and optional 28-36 hours

A measurement of pharmacokinetics which is the area under the curve measured as a function of time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-drug infusion, post drug infusion at 5 minutes, 10 minutes,15 minutes and 20 minute post-drug

Ventricular effective refractory period measured via electrophysiology catheter.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure

Oxygen saturation measured by pulse oximeter, %

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure

Rate of respiration, respiration per minute

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: during procedure

Ventilator measured L/min of ventilation

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: during procedure

Volume of ventilated air, measured as L/breath

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure, two hours post procedure

Blood gas, obtained from arterial blood supply, pH measurement

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-procedure, during procedure, two hours post procedure

Blood gas, obtained from arterial blood supply, mmHg of O2 concentration

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure, two hours post procedure

Blood gas, obtained from arterial blood supply, mmHg of CO2 concentration

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure, two hours post procedure

Blood gas, obtained from arterial blood supply, mmHg of CO2 concentration

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, two hours post procedure

Handgrip strength using a dynamometer; measured in pounds of force

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: During procedure, post drug infusion at 0, 5, 10, 15, 20 minutes

Twitch amplitude; measured as a % of the baseline calibration twitch amplitude (unitless, % change)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure, and two hours post procedure

Bag/mask ventilation, CPAP, BiPAP, LMA, or tracheal intubation

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure and two hours post procedure

Measured by bedside breathing test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure, post drug infusion at 0, 5, 10, 15, 20 minutes, and continuous

Train of four stimulation test measured as a % of the fourth stimulation compared to the first (unitless, % change)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: pre-procedure, during procedure, two hours post procedure

Arterial blood concentrations of sodium, chloride, potassium, ionized calcium, bicarbonate, glucose, and lactate measured in SI ) international system of units.

Outcome measures

Outcome data not reported

Adverse Events

Dantrolene/Ryanodex

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Dantrolene/Ryanodex n=29 participants at risk Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose Dantrolene/Ryanodex: muscle relaxant	Placebo n=22 participants at risk controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose Placebo: Controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose
Cardiac disorders Intensive Care Unit	17.2% 5/29 • Number of events 5 • 24 hours post ablation	9.1% 2/22 • Number of events 2 • 24 hours post ablation

Additional Information

Dr. William Stevenson

Vanderbilt University Medical Center

Phone: 615-322-2318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place