A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias. (NCT04134845), a randomized phase 2, phase 3 study. The primary outcome is Number of Participants With Inducible Sustained Ventricular Tachycardia/ Ventricular Fibrillation (VT/VF) Utilizing Standardized Stimulation Protocol..

2. Clinical Question

The clinical question concerns an immediate electrophysiologic outcome, not a long-term clinical event. The primary outcome is assessed 10 minutes post drug infusion. The registry describes ventricular stimulation using a catheter in the right ventricular apex, with increasing extra stimuli and planned decrement stimuli to the effective refractory period. The result is recorded as inducibility yes or no.

The comparison therefore asks whether the posted number of participants with inducible sustained VT/VF differs between the randomized dantrolene and placebo groups at this assessment. The summary describes the study as evaluating feasibility and exploring electrophysiologic and hemodynamic effects, as well as pharmacokinetic/pharmacodynamic relationships. Those broader aims should not be mistaken for additional primary outcomes in the result.

The registry record does not report a detailed account of the participants who contributed to each outcome beyond the arm counts shown with the result. It also does not report more specific eligibility criteria in the material. Consequently, the result addresses this recorded population and procedure; it does not by itself describe effects in other patient groups or at other times.

3. Trial Design

The registry describes a randomized, double-masked, parallel-group, placebo-controlled study. It lists both PHASE2 and PHASE3. The intervention groups were dantrolene/Ryanodex and placebo. Both regimens were intravenous one-time doses described as 1 mg/kg over 3 minutes. The posted primary outcome is measured 10 minutes post drug infusion.

The registry record lists enrollment as 68. Its brief summary describes a planned study of dantrolene with N= 84 participants. These are different enrollment figures in the record. The primary-outcome result, in turn, lists 29 participants in the dantrolene group and 22 in the placebo group. Those outcome counts are the denominators accompanying the posted comparison; they should not be assumed to represent every enrolled participant or to explain the difference between the enrollment descriptions.

The study status is completed. The record gives a start date of 2020-08-21 and a primary completion date of 2025-05-29. Vanderbilt University Medical Center is listed as the sponsor. The study summary describes a focus on feasibility of using intravenous dantrolene to study RyR2 inhibition and its short-term effects on cardiac electrophysiology, hemodynamics, and ventricular arrhythmia inducibility.

One secondary outcome is posted: stage of inducibility of VT/VF by a standardized ventricular stimulation protocol before and after drug or placebo. The registry lists 27 outcome measures, but only one secondary outcome is identified in the information. It lists no analysis records. Detailed allocation procedures, masking procedures, follow-up beyond the stated assessment, and the protocol’s own sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 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.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Inducible Sustained Ventricular Tachycardia/ Ventricular Fibrillation (VT/VF) Utilizing Standardized Stimulation Protocol., measured over 10 minutes post drug infusion.

The primary endpoint is the number of participants with inducible sustained ventricular tachycardia or ventricular fibrillation using a standardized stimulation protocol. The recorded outcome is binary at the participant level: inducibility is classified as yes or no. The assessment is specified for 10 minutes post drug infusion.

The registry description places a ventricular catheter in the right ventricular apex and describes increasing extra stimuli, with planned decrement stimuli by 10 milliseconds to the effective refractory period. This procedure is intended to assess whether sustained VT/VF can be induced under the specified stimulation conditions. The posted result reports participant counts, rather than the number of stimulation attempts or the stage of inducibility.

As a statistical endpoint, a binary outcome allows the groups to be compared by the proportion of participants with the event, or by a contrast such as a risk difference. The event is inducibility, not spontaneous VT/VF during longer-term follow-up. The endpoint is therefore specific to a test conducted shortly after infusion; it does not directly summarize later arrhythmias, survival, symptoms, or other clinical outcomes. The registry record does not report a separate primary outcome for those measures in the result.

The endpoint is relevant to the stated electrophysiologic study question because it records whether the specified stimulation protocol induces sustained VT/VF. Interpretation should remain tied to that protocol, assessment time, and recorded participants.

7. Results Posted in the Registry

• Dantrolene/Ryanodex: 13.8% (4/29) versus 40.9% (9/22) on control; risk difference -27.1 percentage points (95% CI -51.2 to -3.0), risk ratio 0.34 (0.12–0.95); unadjusted two-proportion z-test p = 0.028.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: inducible sustained VT/VF is recorded as yes or no. A binary result can be summarized as the number of participants with the outcome and the number assessed in each group. The posted arm counts and event counts are displayed in the result tables. This form of summary keeps the outcome tied to participants rather than treating repeated stimulation attempts as independent observations. The registry record does not explain any further handling of repeated procedures or observations.

What does the risk difference express?

A risk difference compares the event proportion in one group with the event proportion in another. It is expressed on the probability scale. Here, the comparison names dantrolene/Ryanodex and reports a negative risk difference, corresponding to fewer recorded inducibility events in that arm than in placebo in the posted results. This is a descriptive direction for the particular outcome comparison; it does not, by itself, establish why the groups differ or how the result applies outside the study setting.

Other scales can describe binary comparisons. A risk ratio compares event proportions as a ratio, while an odds ratio compares event odds. These scales answer related but not identical questions and can have different numerical values. The registry posts risk-ratio and odds-ratio estimates as well as the risk-difference comparison. The accompanying tables allow readers to see the comparison on those scales without treating them as separate endpoints. The record does not state which scale was designated as the main inferential scale in the original analysis plan.

How should the p-value be understood?

In general, a p-value measures how unusual data at least as discrepant as those observed would be under a particular statistical model in which the null hypothesis holds. It depends on the model and test used. A small p-value is not the probability that the null hypothesis is true, and a p-value does not quantify the size or practical importance of a difference. The posted unadjusted p-value is 0.028. The exact test or model behind it is not reported in the registry record, so this page cannot verify its assumptions or reproduce it.

The word unadjusted indicates that the posted p-value is not labeled as adjusted. The record does not specify adjustment for covariates or multiplicity. Readers should therefore avoid assuming that an adjustment was or was not used elsewhere in the trial’s analysis. There are 27 outcome measures listed, while only one secondary outcome is identified. The registry does not report a multiplicity plan.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the method used to construct it, under repeated use of that method. It communicates estimation uncertainty in a way a single point estimate cannot. It is not a guarantee that the true effect lies in the particular interval, and its interpretation depends on the analysis method and assumptions. The posted risk-difference interval stays below zero, but the exact interval endpoints are not repeated. The registry record does not name the interval-construction method.

Precision depends on factors including the amount of information in the data, the frequency of the outcome, and the analysis method. When outcome counts are limited, estimates can be sensitive to small changes in the observed data. General statistical guidance is that an interval should be read for both its direction and the range of effects it allows, rather than as a simple pass/fail label. In this trial, the outcome counts and the posted interval are therefore important companions to the p-value.

Why can over-dispersion matter?

General statistical explanation: over-dispersion arises when observed variability is greater than a model expects. It can make standard errors too small if a model assumes less variability than the data contain, which can in turn make intervals look too narrow and tests look more decisive. Over-dispersion is particularly relevant to some count-data models. The primary endpoint is reported as a binary participant count, and the registry does not report a model or an over-dispersion assessment. This concept is not evidence that over-dispersion occurred in this trial.

The result should also be distinguished from the broader study aims. The summary describes exploration of pharmacokinetic/pharmacodynamic relationships and short-term electrophysiologic and hemodynamic parameters. The primary outcome is inducibility of sustained VT/VF, not a combined measure of those objectives. The registry lists one secondary outcome concerning stage of inducibility before and after drug or placebo. The methods used for that secondary outcome are not reported in the record.

10. Confidence Intervals and Precision

The posted risk-difference confidence interval is entirely below zero. In context, this means the reported interval does not include no difference on the risk-difference scale. The estimate is therefore directionally consistent with fewer inducibility events in the dantrolene/Ryanodex group in the recorded outcome data. The interval is not a statement that the effect is known exactly, and the range of values it permits remains relevant to interpretation.

The registry also posts risk-ratio and odds-ratio estimates with intervals. These alternative scales describe the same binary outcome contrast differently. They should not be read as independent confirmations, because they use the same outcome observations. A reader can compare their directions and uncertainty in the posted statistical displays, while remembering that ratios and differences have distinct interpretations.

General statistical explanation: a confidence interval reflects sampling uncertainty under the method used to calculate it. Its width is affected by the amount of information and the analysis assumptions. Small outcome datasets may yield estimates that are sensitive to the observed counts. The posted result has 4 events among 29 participants in the dantrolene group and 9 among 22 in placebo; the record does not supply detail about the interval method, missing outcomes, or analysis population.

The unadjusted p-value is 0.028, but a p-value does not communicate precision on its own. The confidence interval and the underlying counts provide complementary context. Because the registry record does not report the statistical procedure behind the comparison, the reader cannot evaluate the interval construction from this record alone. The displayed precision should be understood as the precision represented by the posted result, not as a complete account of all uncertainty about study design, conduct, or generalizability.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size table and curve are planning illustrations based on fractions of the observed effect, not a record of the trial’s original design calculations. The listed figures are participants per arm, not total events. The table gives planning values for detecting the observed effect and smaller fractions of it, with separate columns for 80% and 90% power. The record does not provide the trial’s own original sample-size assumptions or justification.

In general, power is the chance that a planned study will identify an effect of a specified size as statistically detectable under its assumptions. The 80% power column gives the planned number of participants per arm for an 80% chance under those assumptions; the 90% column gives the corresponding number per arm for a higher chance. The figures in the table are not observed power and do not describe the probability that this completed trial detected an effect.

The planning assumptions listed are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. These are assumptions for the illustration, not confirmed features of the trial’s original design. The curve provides a visual companion to the table; it should be read as reflecting the same planning exercise rather than as additional trial results.

The table shows that planning for 75% of the observed effect requires more participants per arm than planning for the full observed effect, and planning for 50% requires more again. This is the general relationship: smaller effects are harder to distinguish from random variation, so they require more information for the same power under otherwise similar assumptions. These projections depend on the observed effect used as their starting point and should not be treated as a guarantee of future study performance.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.409; treatment proportion p₁ = 0.138; average p̄ = 0.274.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6304 = 1.2356.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6005 = 0.5054.
4. n = (1.2356 + 0.5054)² / (-0.2712)² = 41.2, rounded up to 42 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.409090909090909                          # control proportion
p1 <- 0.137931034482759                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4134845)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 42 (80% power), 55 (90% power)
 75% of observed effect: n per arm = 80 (80% power), 107 (90% power)
 50% of observed effect: n per arm = 191 (80% power), 255 (90% power)
power.prop.test: 41.2 
Simulated power at n = 42 per arm: 0.818 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists 27 outcome measures and identifies one secondary outcome in the information. The primary outcome is the count of participants with inducible sustained VT/VF using the standardized stimulation protocol. The record does not report a multiplicity strategy, such as how the chance of false-positive findings across multiple outcomes or analyses was addressed. The posted p-value is labeled unadjusted, and it should be read as such rather than as a documented multiplicity-adjusted result.

In general, testing many outcomes can increase the chance of obtaining at least one apparently notable result by chance if each is considered separately. Prespecifying a primary outcome and a strategy for secondary outcomes can help clarify interpretation. The registry information does not establish what strategy was specified in the protocol, whether a statistical analysis plan existed, or whether additional analyses were conducted outside the registry results. Those details are not reported in the registry record.

The record lists no analysis records. It does not say how missing primary outcome data were handled, whether any participants were excluded from the analysis, or whether the outcome analysis followed an intention-to-treat or another population definition. The listed arm denominators are 29 and 22. The separate enrollment field says 68, while the brief summary says N= 84; the record does not explain the relationship between these figures or the outcome denominators.

These missing details matter because analysis populations and missing-data rules can affect which observations contribute to a comparison. They also affect how closely the posted result can be linked to the randomized groups as assigned. No particular missing-data method or analysis population should be inferred from the information shown. The result is best described as the comparison posted for the stated outcome and its listed arm counts, with the analysis details not reported in the registry record.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety display reports serious adverse event figures separately from other adverse events and deaths. In the dantrolene/Ryanodex group, 0 participants are listed with serious adverse events among 29 at risk, 5 with other adverse events among 29 at risk, and 0 deaths. In the placebo group, 0 are listed with serious adverse events among 22 at risk, 2 with other adverse events among 22 at risk, and 0 deaths.

No serious adverse event terms are listed in the record. The displayed figures should be read as the registry’s recorded counts for the groups and categories, not as a complete narrative of event timing, severity, or causality. The record does not report further definitions or details for the other adverse event category in the information.

These counts are descriptive. They do not establish that no unrecorded events occurred, and the group sizes and reporting details constrain interpretation. The safety display is distinct from the primary inducibility outcome and does not explain the efficacy comparison. It should not be used alone to draw broader conclusions about safety beyond the adverse event information posted for this trial.

15. What the Result Does, and Does Not, Mean

The posted primary outcome comparison shows fewer participants with inducible sustained VT/VF in the dantrolene/Ryanodex group than in the placebo group at the assessment 10 minutes post infusion. The counts are 4 among 29 and 9 among 22, respectively. The reported risk difference is negative, its posted confidence interval is below zero, and the unadjusted p-value is 0.028. Together, these describe the recorded short-term result and its statistical uncertainty.

The result does not establish an effect on spontaneous ventricular arrhythmias over time. The endpoint is inducibility under a specified stimulation protocol, not later clinical events or survival. Nor does this comparison establish effects on all electrophysiologic or hemodynamic parameters mentioned in the study summary. The registry record does not provide the results of those measures in the information.

The result also does not settle how applicable the findings are to people outside the study population. The registry describes patients with structural heart disease referred for VT ablation, but detailed eligibility criteria and a complete account of the analyzed population are not reported. The difference between the enrollment descriptions and outcome denominators is not explained.

Statistical evidence should not be equated with clinical importance. A p-value does not say how meaningful an effect is to patients, and the endpoint is a short-term procedural measure. The posted interval conveys uncertainty about the size of the risk difference under the analysis method, but the record does not give the method used to construct it. The data therefore support a description of this specific observed contrast, not a broad claim about treatment benefit, long-term outcomes, or safety.

16. Why This Trial Matters Statistically

This trial is statistically interesting because it places a randomized, placebo-controlled comparison around a clearly defined binary electrophysiologic endpoint. The primary result is based on whether sustained VT/VF was inducible under a standardized stimulation protocol shortly after infusion. That makes the outcome and assessment time concrete, while also limiting the scope of the conclusion to that procedure and time point.

The posted counts show why a point estimate should be read with its uncertainty. The risk difference is reported with a confidence interval, and the unadjusted p-value is shown alongside the group counts. Each conveys different information: counts describe the data, an effect estimate summarizes the contrast, an interval describes estimation uncertainty, and a p-value describes compatibility with a specified null model under the test used. None alone provides a complete interpretation.

The record also highlights practical issues in registry-based analysis. Enrollment is described differently in the enrollment field and brief summary, while the outcome result has its own listed arm counts. The registry does not explain how these figures relate. It also does not report the analysis procedure, missing-data handling, analysis population, or multiplicity plan. Such gaps make transparent reporting important for evaluating how results were generated.

Finally, the sample-size display is explicitly a planning illustration based on the observed effect, not the trial’s documented design calculation. It shows how planning assumptions and the effect size of interest shape required sample sizes. Keeping that distinction clear helps prevent a retrospective illustration from being mistaken for the trial’s original design rationale or for observed power.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several trial-specific uncertainties. The enrollment field lists 68, while the brief summary says N= 84, and the posted primary outcome lists 29 participants in the dantrolene group and 22 in placebo. The record does not reconcile these figures or explain the outcome denominators. It does not report detailed eligibility criteria, participant flow, or reasons participants may not appear in the outcome counts.

The analysis method for the primary comparison is not described. The record does not identify the test or model used for the unadjusted p-value, the method for constructing confidence intervals, whether covariates were considered, or the analysis population. It does not report missing-data procedures or the protocol’s multiplicity plan. No analysis records are listed, which limits the statistical detail available in the registry entry.

The primary endpoint is a short-term measure of inducibility assessed 10 minutes post infusion under a stimulation protocol. It is not a measure of spontaneous arrhythmia events over longer follow-up. The registry summary mentions broader electrophysiologic, hemodynamic, and pharmacokinetic/pharmacodynamic aims, but the results for these measures are not included in the information. Only one secondary outcome is identified despite the listing of 27 outcome measures.

The adverse event display is limited to counts for serious adverse events, other adverse events, and deaths. It does not provide event descriptions, timing, severity details, or causal assessments in the information. These limitations do not negate the posted findings; they define what can and cannot be concluded from this registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias. — NCT04134845.
• Registry record last updated 2026-10-08; status last verified 2026-09.
• Results first posted 2025-08-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry describes a completed randomized, double-masked, parallel-group trial comparing intravenous dantrolene/Ryanodex with saline placebo in patients with structural heart disease referred for VT ablation. The primary outcome is the number of participants with inducible sustained VT/VF using a standardized stimulation protocol 10 minutes post infusion.

The posted result lists 4 events among 29 participants in the dantrolene group and 9 among 22 in placebo. The risk-difference interval is reported zero, and the unadjusted p-value is 0.028. Serious adverse events and deaths are listed as 0 in both groups; other adverse events are listed for 5 dantrolene participants and 2 placebo participants.

The record lists enrollment as 68, while its brief summary says N= 84. The outcome denominators and the analysis details are not reconciled or fully described. The result is specific to the short-term inducibility endpoint and should be interpreted with the registry’s reporting limitations in view.