Electrical Stimulation for Critically Ill Covid-19 Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Electrical Stimulation for Critically Ill Covid-19 Patients (NCT04685213), a randomized phase 1 study. The primary outcome is Change in Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation.

2. Clinical Question

The study was framed as a feasibility and proof-of-concept randomized controlled trial. Its rationale was that maintaining muscle activity with electrical stimulation might be practical when conventional mobility programs are challenging in intensive care. That rationale is not itself evidence of benefit: the clinical question is whether the posted outcome summaries distinguish the active and sham groups, and how much uncertainty surrounds that distinction. The registry record does not report a formal test or interval estimate for the primary comparison, so the summaries alone cannot answer that inferential question.

3. Trial Design

The registry identifies this study as a Phase I, randomized, double-masked, parallel-group trial. Its title describes electrical stimulation therapy for preventing hospital-acquired weakness in critically ill patients with COVID-19. The record lists Baylor College of Medicine as sponsor and marks the study completed. Enrollment was 19. The registry dates the start to 2020-12-22 and primary completion to 2021-03-18.

Participants were assigned to active E-Stim or sham E-Stim. The stated treatment schedule for both groups was 1 hour of device wear daily for up to two weeks or until hospital discharge, whichever came first. Although the record labels masking as double, it does not specify which people involved in the trial were masked or how the sham device differed from the active device. Allocation concealment and the randomization procedure are not reported in the registry record.

The primary outcome was change in gastrocnemius muscle endurance, measured in millivolts and described as sustained contraction in response to electrical stimulation. The listed timeframe was an average of 2 weeks in Phase I. The outcome description says that endurance in response to 5 minutes of stimulation would be assessed with surface electromyography using a validated, non-invasive device. The record does not give additional details about measurement timing, assessor procedures, or how change was calculated.

The posted primary-outcome summaries list 8 participants in each group: the active group has a mean of 352.0 millivolts and a standard deviation of 37.0, while the sham group has a mean of 323.0 millivolts and a standard deviation of 18.0. The relationship between these outcome summaries and the enrollment figure of 19 is not explained in the registry record. It does not identify the analysis population or explain whether any participants lacked an outcome measurement.

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.

Overall Study

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 Change in Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation, measured over an average of 2 weeks (Phase I).

The primary endpoint concerns gastrocnemius muscle endurance, described as sustained contraction in response to electrical stimulation. The registry reports the outcome as a continuous measure in millivolts. Its stated assessment uses surface electromyography, a method for recording electrical activity from muscle through surface sensors. The registry describes assessment during a 5-minute stimulation procedure and gives an average of 2 weeks in Phase I as the outcome timeframe.

A continuous measurement can retain information about the magnitude of a recorded response rather than reducing each participant’s result to a category. For that reason, the group mean can describe the average measured response, while the standard deviation describes how spread out the observed measurements are around that mean. These summaries do not, on their own, indicate how precisely the group means estimate the underlying values or whether a difference between groups is compatible with chance variation.

Muscle endurance is relevant to the trial’s stated concern about muscle deconditioning and hospital-acquired weakness. However, the measured endpoint is a physiological outcome, not a direct report of functional status after discharge. The registry also lists change in plantar tissue oxygen saturation or consumption as a secondary outcome. It does not report an inferential analysis connecting the primary muscle measure to later function, hospital-acquired weakness, or other patient-centered outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome summarized by a mean and standard deviation. Understanding what these statistics describe helps separate the recorded data from the conclusions that would require an inferential analysis.

What does the mean describe?

A mean is the arithmetic average of the measurements in a group. Here, the reported means are 352.0 millivolts for active E-Stim and 323.0 millivolts for sham E-Stim. A mean provides a compact description of the group’s measured values. It does not show the full distribution: different patterns of individual observations can produce the same average.

The mean is also not automatically an estimate of a treatment effect. A treatment contrast requires comparing groups under a defined analysis, with a specified approach to the outcome and the randomized assignment. The posted group means are useful descriptive information, but the registry record does not report a formal estimate or test of the between-group contrast.

What does the standard deviation describe?

The standard deviation describes the spread of the observed measurements around their group mean. The reported standard deviations are 37.0 millivolts for active E-Stim and 18.0 millivolts for sham E-Stim. A larger standard deviation indicates more dispersion in the observations relative to that group’s mean; it does not say whether the mean difference is statistically persuasive. A standard deviation is not the same as a confidence interval or standard error.

General statistical explanation: a confidence interval expresses uncertainty around an estimate using a procedure with stated assumptions. It helps readers assess both the range of effects compatible with the data and the precision of the estimate. No confidence interval for the primary comparison is reported in the registry record. As a result, the precision of the comparative result cannot be evaluated from the posted primary summaries alone.

Why does the analysis population matter?

The posted summaries list 8 participants for each group, while the study enrollment is 19. The record does not explain whether the outcome summaries include all randomized participants, only participants with measurements, or another defined population. It also does not state how missing measurements were handled. General statistical explanation: when outcomes are missing, the analysis can depend on why they are missing and on the assumptions made about unobserved measurements. A clear account of the analysis population and missing-data approach helps readers judge the potential for bias.

For a randomized trial, an analysis based on the assigned groups can preserve the benefits of random allocation, but the registry record does not say whether that approach was used. It does not report a per-protocol analysis or another analysis population either. The group summaries should therefore be interpreted as posted summaries, without assuming a particular population definition.

What can a test or interval add?

A test of a group contrast addresses whether the observed data are inconsistent with a specified null hypothesis under the test’s assumptions. A p-value is one part of that assessment; it does not measure the size or clinical importance of an effect. A confidence interval adds an estimate of the range and precision of a contrast. Neither a p-value nor a confidence interval is reported for the primary comparison. A test result would also not, by itself, establish that a measured difference is clinically meaningful.

General statistical explanation: small studies commonly yield imprecise estimates, because there is limited information with which to distinguish an underlying group difference from random variation. This is a general consideration, not a numerical estimate of uncertainty for this trial. The registry record gives no interval or standard error that would quantify that uncertainty for the primary endpoint.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also describes considering a stated fraction of the observed effect. Such an illustration is conditional on its assumptions; it is not the trial’s own design justification, and it is not observed power. No sample-size justification or detailed power plan is reported in the registry record. The posted record gives no basis for treating a planning illustration as evidence that the completed study had adequate precision.

General statistical explanation: planning calculations estimate the amount of information needed to detect a specified effect under chosen assumptions. They do not establish the probability that a completed study has found a true effect, and they cannot replace reporting an estimate and its uncertainty. The registry record does not report a formal inferential analysis for this outcome. It also does not report interim analyses or a detailed statistical plan, so neither should be presumed.

Why might over-dispersion matter?

General statistical explanation: over-dispersion occurs when variability in the data is greater than a model expects. If a model fails to account for that extra variability, its uncertainty estimates can be too small and its inferential results too confident. The primary outcome is continuous and summarized with a mean and standard deviation; the registry record does not report a model or an over-dispersion assessment. There is therefore no basis for claiming that over-dispersion affected this analysis. The broader point is that uncertainty estimates depend on whether the analysis method matches the data and design.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Active E-Stim (Phase I)", "Sham E-Stim (Phase I)")
n   <- c(8, 8)
m   <- c(352, 323)
sp  <- c(37, 18)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Active E-Stim (Phase I)  8  352.000  37.000  321.067  382.933
CARM  Sham E-Stim (Phase I)  8  323.000  18.000  307.952  338.048

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and names change in plantar tissue oxygen saturation or consumption as a secondary outcome. It does not report a multiplicity adjustment, a hierarchy among outcomes, or a plan for controlling the chance of false-positive findings across multiple comparisons. The record reports 0 analyses. This means no inferential analyses are posted in the registry record; it does not establish that no analyses were conducted outside the record.

The registry’s note says values are missing or not estimable for a two-arm comparison of the continuous endpoint. The primary arm summaries are nevertheless posted as means and standard deviations. No inferential two-arm comparison is reported. The record does not explain why a comparison was unavailable or not estimable, and it does not state whether other outcome measures were analyzed. Detailed results for the named secondary outcome are not reported in the registry record.

Missing-data methods and analysis populations are also not described. The record does not explain how the primary summaries relate to the enrollment of 19, or whether any participants lacked endpoint measurements. It does not report imputation, a complete-case approach, or sensitivity analyses. These details matter because the interpretation of a randomized comparison can depend on who is included and how unavailable measurements are treated.

The registry record does not describe a prespecified analysis plan, outcome-selection procedures, or how multiplicity would be handled. Without those details, readers cannot determine whether the posted results represent all planned analyses or how selective reporting was addressed. This uncertainty should not be resolved by assuming a particular protocol or analysis strategy.

12. 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.

For active E-Stim, the registry lists 9 participants at risk for serious adverse events and 0 affected; for sham E-Stim, it lists 10 at risk and 0 affected. For other adverse events, it likewise lists 9 at risk and 0 affected in the active group, and 10 at risk and 0 affected in the sham group. These are the registry’s reported counts. They should not be converted into rates or treated as a comparative safety analysis.

The death counts are listed separately: 1 in the active group and 3 in the sham group. The record does not explain the relationship between these death counts and the adverse-event counts, provide event timing, or report attribution to the intervention. It also does not provide an analysis comparing mortality between groups. The counts are therefore descriptive and do not show that electrical stimulation caused, prevented, or had no effect on deaths.

Safety data from a small Phase I trial can be useful for documenting what was recorded, but the absence of reported adverse events is not proof that an intervention is free of risk. The registry record does not provide detailed event descriptions or follow-up information. Readers should distinguish the adverse-event counts from the separate death counts and avoid interpreting either as a causal estimate.

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

The registry record establishes that this randomized Phase I study posted descriptive results for a continuous measure of gastrocnemius muscle endurance. The active-group mean was 352.0 millivolts, with a standard deviation of 37.0; the sham-group mean was 323.0 millivolts, with a standard deviation of 18.0. Each summary lists 8 participants. These values describe the recorded groups and the spread of their measurements.

They do not establish whether the groups differed statistically or how precisely a comparative effect was estimated. The registry does not report a confidence interval, p-value, or inferential estimate for the primary comparison. It also does not explain how the outcome summaries relate to the enrollment of 19. Without those details, the magnitude and uncertainty of a treatment contrast cannot be fully assessed.

The endpoint measures muscle electrical activity during an assessment, not the full clinical experience of patients with COVID-19. The record does not report a direct analysis of hospital-acquired weakness, post-discharge function, or a link between the primary outcome and those outcomes. The named secondary outcome concerns plantar tissue oxygen saturation or consumption, but no inferential result for it is reported.

The study’s proof-of-concept framing and completed status do not change these limits. The results do not establish that active stimulation prevents weakness, improves recovery, or has no effect. Nor do the adverse-event and death counts establish a comparative safety effect. The record is informative about what was posted, but its descriptive summaries and limited analysis do not support a definitive clinical conclusion.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction in biostatistics: reporting group summaries is not the same as reporting a comparative analysis. Means and standard deviations communicate the observed outcome levels and variability, but they do not quantify the uncertainty in a treatment contrast. Without an estimate, confidence interval, or test result, readers cannot assess the precision of the comparison using the registry record alone.

It also illustrates why a clear account of analysis populations matters. Enrollment is reported as 19, whereas the primary summaries list 8 participants in each group. The record does not explain the relationship between those figures. Without that explanation, readers cannot tell how the posted outcome summaries map to the enrolled or randomized population, or how missing measurements may have been handled.

The trial’s early-phase, proof-of-concept framing makes transparent reporting particularly useful. The intervention and sham schedules are described, and the primary physiological measure is identified. At the same time, the record does not provide the statistical plan, sample-size justification, multiplicity approach, or inferential results. Clear reporting of these elements would help readers distinguish exploratory description from evidence intended to support a comparative claim.

For clinical researchers, this record is a reminder to interpret the design, outcome, analysis, and safety information together. A randomized design is valuable, but randomization alone does not supply an estimate of effect or resolve uncertainty when the analysis is not reported. The study’s results are best understood as a limited descriptive contribution to an early research question, with substantial unanswered questions about comparative precision and interpretation.

15. 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 has important limitations specific to interpreting this trial. Although it reports randomized, double-masked, parallel-group design, it does not describe the randomization method, concealment, or which trial participants or staff were masked. The device schedules are described, but the record does not explain the sham device’s distinguishing features.

The primary endpoint is defined as a change in gastrocnemius muscle endurance, yet the record does not provide a detailed account of baseline and follow-up measurement procedures or how change was calculated. The stated timeframe is an average of 2 weeks in Phase I, while treatment could end at discharge. The record does not explain how varying observation periods were handled in the endpoint analysis.

Enrollment was 19, but each primary outcome summary lists 8 participants. The registry does not reconcile these figures, define the analysis population, or report how missing values were handled. It also does not report an inferential comparison, confidence interval, or p-value. Consequently, the descriptive summaries do not provide a quantified estimate of comparative uncertainty.

The record names one secondary outcome and lists 5 outcome measures, but does not report a multiplicity strategy or detailed results for that secondary outcome. It does not provide the statistical analysis plan, sample-size justification, interim-analysis information, or sensitivity analyses. The adverse-event record is also limited: it reports counts but not detailed event descriptions, timing, attribution, or a comparative safety analysis. These omissions constrain both statistical and clinical interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Electrical Stimulation for Critically Ill Covid-19 Patients — NCT04685213.
• Registry record last updated 2023-02-16; status last verified 2023-02.
• Results first posted 2022-01-18.
• 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.

19. Record Summary

The registry describes NCT04685213, a completed Phase I randomized, double-masked, parallel-group trial sponsored by Baylor College of Medicine. Enrollment was 19. The study compared active electrical stimulation with sham stimulation in critically ill patients with COVID-19, using a stated schedule of 1 hour daily for up to two weeks or until hospital discharge, whichever came first.

The primary outcome was change in gastrocnemius muscle endurance in millivolts, assessed using surface electromyography. Posted group summaries list 8 participants in each group. The active group mean was 352.0, with a standard deviation of 37.0; the sham group mean was 323.0, with a standard deviation of 18.0. No inferential comparison is reported in the registry record.

The record lists change in plantar tissue oxygen saturation or consumption as a secondary outcome. It reports no serious or other adverse events in either group and separately lists deaths of 1 in the active group and 3 in the sham group. These counts are descriptive. The registry does not report an analysis population, missing-data approach, confidence interval, p-value, or detailed statistical plan.