Breath Synchronized Abdominal Muscle Stimulation to Facilitate Ventilator Weaning: a Pilot Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Breath Synchronized Abdominal Muscle Stimulation to Facilitate Ventilator Weaning: a Pilot Study (NCT03019107), a randomized phase not stated study. The primary outcome is Change in Maximum Expiratory Pressure From Baseline to Extubation.

2. Clinical Question

3. Trial Design

The study, NCT03019107, was titled Breath Synchronized Abdominal Muscle Stimulation to Facilitate Ventilator Weaning: a Pilot Study. It was registered as a randomized, triple-masked, parallel-group pilot study sponsored by Liberate Medical. The listed interventions were breath-synchronized abdominal NMES and sham breath-synchronized abdominal NMES, under the arm names VentFree Stimulation and Sham Stimulation. These are descriptions of the intended comparison; the posted primary outcome record indicates that the sham arm enrolled no patients.

The registry lists enrollment of 2 and a study start date of 2017-02-22. Primary completion is recorded as 2017-04-06, and the study status is TERMINATED. The record does not state why the study was terminated, and a reason should not be inferred from the status or the enrollment pattern. The primary outcome was change in maximum expiratory pressure from baseline to extubation. Secondary outcomes covered abdominal muscle thickness, diaphragm thickness, weaning success, days taken to wean, and cough peak flow.

The arm-level primary results list 1.0 participant in VentFree Stimulation with a value of 2 cmH2O, while Sham Stimulation has 0.0 participants and no value. The record lists 15 outcome measures, 13 posted secondary outcomes, and 0 analyses. The relationship between the count of outcome measures and the count of posted secondary outcomes is not explained in the registry record. These design and result details distinguish the intended randomized comparison from what is available for interpretation: a primary value in one arm, but no observed sham result for a between-arm comparison.

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

Analysis population for the primary outcome, as defined in the registry: No patients were enrolled in the sham arm

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.

Population: No participants were enrolled in the control group as the trial was terminated after the first patient was enrolled.

6. Primary Endpoint

The registry lists the primary outcome as Change in Maximum Expiratory Pressure From Baseline to Extubation, measured over Change from baseline to first extubation, an expected average of 4 weeks.

The primary endpoint was change in maximum expiratory pressure from baseline to first extubation. The registry states that pressure was measured from total lung capacity and gives cmH2O as the unit. Maximum expiratory pressure assesses the ability to generate pressure during expiration, so it serves as a measure of expiratory muscle performance. In this study, that measurement was selected in relation to the objective of assessing respiratory muscle strength during prolonged mechanical ventilation.

The specified timeframe was change from baseline to first extubation, described as an expected average of 4 weeks. This is the planned measurement window; it does not establish the actual time observed for the participant. Because extubation is part of the endpoint timeframe, interpretation can depend on whether and when that event occurs. The registry record does not report a separate outcome value for each measurement occasion or further details about the measurement procedure.

The posted primary result is 2 cmH2O for VentFree Stimulation, with 1.0 participant listed in that arm. No sham participant was enrolled, and no sham value is listed. The record therefore offers a single-arm result rather than a contrast in change between randomized groups. A change measure can describe movement from baseline, but a treatment comparison requires outcome information from both groups and a suitable comparative analysis. Neither is available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing the intended study design from the outcome data that are available. The registry classifies the trial as randomized, triple-masked, and parallel. In general, randomization is intended to reduce systematic differences between treatment groups at assignment, masking can reduce certain sources of influence on care or assessment, and a parallel design assigns participants to a group whose intervention is followed over the study period. These design labels describe the planned structure; they do not guarantee that a comparative analysis can be made from the posted results.

What does randomization contribute?

In general, randomization supports a fair comparison by making assignment independent of known and unknown participant characteristics on average across repeated assignments. It does not ensure that groups will be balanced in every small study, and it cannot compensate for an arm with no outcome observations. Here, the sham arm lists 0.0 participants for the primary result. Consequently, the record contains no observed sham outcome against which to compare the stimulation-arm value. The randomized designation remains a fact about the design, but it cannot supply the missing comparator data.

What does the primary result represent?

The primary endpoint is change in maximum expiratory pressure from baseline to first extubation, measured from total lung capacity and expressed in cmH2O. The arm result lists 2 cmH2O for VentFree Stimulation and 1.0 participant. This is a descriptive result from the stimulation arm as recorded. A treatment effect in a randomized trial ordinarily refers to a contrast between outcomes under the intervention and comparator, using a defined measure and analysis. No such contrast is posted. The registry record also does not report a confidence interval or another measure of uncertainty for the arm value.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical model and procedure. Its width conveys how precisely an effect has been estimated: a wider interval indicates greater uncertainty, while a narrower interval indicates greater precision under those assumptions. An interval cannot be recovered from an arm value alone without the relevant information and method. No interval is listed for the primary endpoint, and the absence of a sham result means that comparative uncertainty cannot be quantified from the registry record.

In general, a p-value assesses how compatible data are with a specified null hypothesis under a statistical model; it is not the probability that a treatment works or that the null hypothesis is true. A p-value also does not measure the size or clinical importance of an effect. The registry record reports 0 analyses and no p-value for the primary outcome. It therefore offers no basis for a significance test of a stimulation-versus-sham effect. A missing p-value should not be read as evidence for either a positive or a negative comparative result.

Why does the absence of an arm matter?

A two-group comparison requires outcome information from both groups. With no sham participants listed, a comparison would have no sham mean, median, event count, or other outcome summary to use. Methods that adjust for covariates or account for variability cannot manufacture the absent comparator observations. The record does not report any alternate control group, external comparator, or model-based estimate. No comparative effect should therefore be inferred from the single-arm value.

In general, the choice of model depends on the endpoint type, its distribution, the design, and the question being asked. A continuous measure may be analyzed through a difference in means or another suitable summary, while a count or time-to-event measure may call for other methods. Data can also show more variability than a simple model expects; over-dispersion means that the observed variation exceeds the model's assumed variation and can make standard errors too small if ignored. These are general principles, not descriptions of analyses conducted for this trial. The record does not specify a model, distributional assumptions, covariate adjustment, or methods for handling variation.

The planning illustration described in the registry uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with an effect to detect expressed as a fraction of the observed effect. It specifies that non-time-to-event entries are participants per arm and time-to-event entries are total events. These are planning assumptions, not the trial's observed analysis and not evidence of achieved power. No sponsor sample-size justification or actual statistical plan is reported in the registry record. Without a usable comparative estimate, planning calculations based on an observed effect would not remedy the lack of a sham result.

The registry identifies 15 outcome measures, 13 posted secondary outcomes, and 0 analyses. The record does not explain the difference between those outcome counts, and it does not state which analysis populations were used. These omissions matter because a listed outcome is not the same as a completed analysis. Interpreting a result requires knowing which participants contributed, how measurements were summarized, and what method was specified. Those details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 13 posted secondary outcomes. The secondary outcomes include changes in thickness of the transverse abdominis, external oblique, and internal oblique muscles from baseline to extubation; thickness of the rectus abdominis and diaphragm; weaning success; days taken to wean; and change in cough peak flow from baseline to extubation. The record does not explain the relationship between the outcome-measure count and the posted-secondary-outcome count, or identify which secondary outcomes have usable results.

When a study evaluates several outcomes, multiplicity can arise from conducting multiple statistical tests. In general, the chance of at least one apparently notable finding can increase as more tests are considered, unless the analysis plan accounts for this issue. The record does not report a multiplicity adjustment, a hierarchy of outcomes, or a prespecified strategy for interpreting multiple tests. It also lists 0 analyses, so the posted record does not offer a set of inferential results to evaluate for multiplicity.

Missing data and analysis populations are also not described in enough detail to reconstruct an analysis. The primary outcome record says no patients were enrolled in the sham arm. It does not state whether the value in the stimulation arm represents all randomized participants, all treated participants, or another population. The registry record does not report reasons for missing measurements, imputation methods, sensitivity analyses, or whether participants were analyzed according to randomized assignment. It is not appropriate to infer any of these procedures from the randomized designation or the reported arm counts.

Because the primary endpoint is defined through first extubation, the record's stated timeframe does not clarify how an outcome would be handled if extubation did not occur. Such handling, along with the timing of actual measurements, is not reported in the registry record. These gaps limit interpretation of both the primary and secondary outcomes.

11. 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 serious adverse event figures list 0 serious adverse events among 1 participant at risk in VentFree Stimulation. For Sham Stimulation, the record lists 0 participants at risk and 0 serious adverse events. The sham figures therefore do not represent observed safety experience among enrolled sham participants; no patients were enrolled in that arm according to the primary outcome population description. The record lists 0 deaths in each arm.

The adverse-event fields also report 1 other adverse event among 1 participant at risk in VentFree Stimulation, and 0 among 0 at risk in Sham Stimulation. The record does not list a serious adverse event term. These counts describe what is posted; they do not establish event rates for a broader population or permit a meaningful safety comparison between arms. In particular, a zero count with no participants at risk in an arm should not be interpreted as evidence that the intervention or comparator had no adverse events.

In general, adverse-event counts depend on the number of participants observed, the observation period, and how events are defined and collected. The registry record does not provide further details about event timing, severity beyond the serious/non-serious grouping, relatedness, or the nature of the other adverse event. With the small amount of recorded exposure and no enrolled sham participants, the safety information is highly limited.

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

The record documents a pilot study designed to compare breath-synchronized abdominal muscle stimulation with sham stimulation during ventilator weaning. It records a primary endpoint of change in maximum expiratory pressure from baseline to first extubation and a value of 2 cmH2O in VentFree Stimulation. These registry entries describe the intended question and the available arm-level result. They do not provide a comparative estimate of what stimulation changed relative to sham.

The central interpretive constraint is that the sham arm has 0.0 participants in the posted primary outcome result and no outcome value. A randomized comparison needs data from the comparator as well as the intervention group. Without that information, the observed value cannot be attributed to the intervention by comparing outcomes across arms, and the magnitude or precision of a treatment effect cannot be estimated from the record. The registry also lists 0 analyses, with no inferential test or interval for the primary endpoint.

The record does not explain why the trial was terminated, why sham enrollment was absent, or how the overall enrollment entry relates to the arm-level primary outcome fields. These unknowns should remain unknown rather than being filled in from assumptions. The status TERMINATED and the completion date 2017-04-06 are registration details, not explanations of the trial's conduct or results.

The study's findings therefore have a narrow descriptive meaning: a primary value is posted for the stimulation arm, while no sham outcome is posted. They do not establish that stimulation increases respiratory muscle strength, does not increase it, or produces any particular effect on weaning. They also do not establish comparative safety. The adverse-event counts are limited by the absence of sham participants and the very limited recorded exposure. The registry record is informative about the study's question and the incompleteness of its comparative evidence, but not about a reliable between-group treatment effect.

13. Why This Trial Matters Statistically

This study is statistically important as an example of the distinction between a randomized design and an interpretable randomized comparison. Randomization can be a strong basis for comparing groups when each group contributes outcome data. Here, the registry record classifies the trial as randomized, triple-masked, and parallel, yet the sham arm lists 0.0 participants for the primary endpoint. A design label alone cannot replace the observations required to estimate a contrast.

The record also illustrates why an outcome value needs context. The VentFree Stimulation result is 2 cmH2O, but without a sham result, a measure of variability, or an inferential analysis, that number is a single-arm description rather than evidence of a comparative effect. Readers need to distinguish an observed group value from a treatment-effect estimate and to look for uncertainty information before drawing conclusions about precision.

Several outcomes were registered or posted, including respiratory muscle measures and indicators related to weaning. Considering multiple outcomes can make a statistical interpretation more complex, especially when a prespecified analysis strategy is unavailable. In this record, the number of analyses is 0, and multiplicity methods are not reported. This makes it especially important not to treat the presence of an outcome list as evidence that the outcomes were analyzed or that findings were established.

Finally, the safety counts show how denominators matter. A count of 0 events in a group with 0 participants at risk is not observed evidence of an event-free group. Clear reporting of enrolled populations, outcome availability, analysis methods, and reasons for missing information is essential for understanding what a trial can support. The record's limited comparative data are themselves a useful reminder that statistical conclusions depend on the information actually available, not solely on the intended design.

14. 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 principal limitation is the lack of a sham-arm primary outcome: the record lists 0.0 participants and no value in that arm. This prevents estimation of the intended randomized comparison. The VentFree Stimulation arm lists 1.0 participant and a value of 2 cmH2O, but no confidence interval, standard error, or other uncertainty summary is reported. The registry also lists 0 analyses, so there is no posted inferential result for the primary endpoint.

Enrollment is recorded as 2, while the primary outcome arm entries list 1.0 and 0.0 participants. The registry record does not explain how these figures relate, which participants were included in the endpoint result, or whether measurements were missing. It does not report an analysis population, a missing-data approach, or details of the actual measurement schedule. The timeframe is described as an expected average of 4 weeks; the actual time to measurement is not reported in the registry record.

The study status is TERMINATED, but the reason for termination is not reported in the registry record. The record likewise does not report a sponsor sample-size justification, statistical analysis plan, multiplicity strategy, or the rationale for any analysis decisions. The listing of 15 outcome measures and 13 posted secondary outcomes is not accompanied by an explanation of their relationship or a set of analysis results.

Safety interpretation is constrained by the same small amount of recorded exposure: the sham group has 0 participants at risk, and the record provides little detail about the other adverse event in the stimulation arm. These limitations make the record descriptive rather than a basis for precise comparative conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Breath Synchronized Abdominal Muscle Stimulation to Facilitate Ventilator Weaning: a Pilot Study — NCT03019107.
• Registry record last updated 2021-11-08; status last verified 2021-10.
• Results first posted 2021-11-08.
• 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.

18. Record Summary

NCT03019107 was a randomized, triple-masked, parallel pilot study sponsored by Liberate Medical, comparing breath-synchronized abdominal NMES with sham breath-synchronized abdominal NMES. The stated primary endpoint was change in maximum expiratory pressure from baseline to first extubation, measured from total lung capacity and expressed in cmH2O. Its timeframe was an expected average of 4 weeks.

The record lists enrollment of 2, a start date of 2017-02-22, primary completion on 2017-04-06, and status TERMINATED. For the primary result, VentFree Stimulation lists 1.0 participant and a value of 2 cmH2O; Sham Stimulation lists 0.0 participants and no value. The record lists 15 outcome measures, 13 posted secondary outcomes, and 0 analyses.

Because no sham outcome is posted, the primary result cannot be interpreted as a randomized between-arm effect. A reason for termination, analysis plan, and details of missing data are not reported in the registry record.