Evaluating Air Leak Detection in Intubated Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating Air Leak Detection in Intubated Patients (NCT01857986), a randomized na study. The primary outcome is CO2 Leakage Above the ETT Cuff, Measured Over Time..

2. Clinical Question

The trial’s stated effectiveness question concerns leakage between the endotracheal tube and tracheal walls, with cuff-pressure management as the intended mechanism of the investigational system. The registry also identifies adverse events as a safety measure and lists a secondary measure concerning cuff-pressure measurements within an accepted range. The posted primary comparison is the evidence to use when describing the leakage outcome; the existence of a randomized comparison does not by itself establish that every aspect of the intervention was isolated or that the outcome captures all clinically relevant effects. Further detail about the participant characteristics and the complete control procedures is not reported in the registry record.

3. Trial Design

This was a randomized, single-masked, parallel-group trial listed as completed. Its enrollment was 76. The registry lists critical care as the condition and Hospitech Respiration as the sponsor. The study began in 2013-09, and primary completion was recorded in 2015-03. The phase is listed as not applicable.

Participants were assigned to a study group or a control group. In the study group, the AnapnoGuard 100 control unit operated in normal clinical mode. The control group used the same unit with cuff-pressure control switched off, with cuff management described as following standard of care. The trial summary explains that the primary outcome could only be measured using the investigational device, which is why both groups were connected to the device. The record calls the study single-masked but does not identify which people were masked or describe how masking was maintained. Those details are not reported in the registry record.

The primary outcome was followed during endotracheal intubation. The stated timeframe says that participants would be followed for the duration of intubation, with an expected average of 4 days. This is an expected duration, not a reported average observed in the posted results. The study summary describes effectiveness in terms of the duration and level of carbon dioxide leakage around the cuff. Safety was to be measured by adverse events.

Although enrollment was 76, the primary outcome groups in the posted comparison contain 34 participants in the study group and 30 in the control group. The record does not explain the difference between enrolled participants and the numbers contributing to this outcome. It does not report participant flow, exclusions from the outcome analysis, or an analysis-population definition. The posted result therefore needs to be read with its group sizes in mind rather than treated as if every enrolled participant necessarily contributed an endpoint value.

The registry lists one secondary outcome, the number of cuff-pressure measurements within the safety accepted range (24 and 40cmH2O). Detailed secondary results are not included in the registry record described for this analysis. Further protocol details, including the original statistical design assumptions and the roles of those masked, 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.

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 CO2 Leakage Above the ETT Cuff, Measured Over Time., measured over Subjects will be followed for the duration of endotracheal intubation, an expected average of 4 days.

The primary endpoint is titled “CO2 Leakage Above the ETT Cuff, Measured Over Time.” It represents each patient’s exposure to carbon dioxide leakage above the cuff, expressed as [CO2 mmHg*hour]/hour. The record describes calculating an area under the curve from carbon dioxide level and leakage duration, then dividing by the patient’s number of hours in the trial. The measurement is based on carbon dioxide readings above the cuff obtained by the AnapnoGuard 100 system every few minutes in clinical mode. Adjacent time intervals with valid readings form the time points used for the curve.

This endpoint is intended to capture both how much leakage is measured and how long it occurs, while standardizing the accumulated exposure by time in the trial. That makes the posted result a continuous patient-level quantity summarized by a mean and standard deviation for each group. It differs from a simple count of leakage episodes: the construction uses a level-by-duration area rather than only whether leakage occurred.

The registry’s rationale is that cuff-pressure management may affect leakage between the tube and tracheal walls. The endpoint therefore addresses a central device-effectiveness question described in the trial summary. Because the measurement depends on the investigational system, the control group was also connected to the unit, with cuff control disabled. The record does not report a separate measurement method for validating the device’s readings, nor does it report a threshold for interpreting an individual endpoint value. The posted group means should consequently be understood as summaries of this specific device-measured outcome, not as a complete account of all possible outcomes during intubation.

7. Results Posted in the Registry

• Study: mean 0.09 versus 0.22 on control; difference -0.13 (95% CI -0.25 to -0.01), standardized effect d = -0.59; z-test p = 0.027.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant has a numerical measure of carbon dioxide leakage standardized per hour. The registry reports a mean and standard deviation for each group. A mean describes the average endpoint value in a group, while a standard deviation describes how dispersed participant values are around that mean. They answer different questions: the mean summarizes the group’s central level, and the standard deviation indicates variability among participants.

What does the mean difference describe?

The comparison is expressed as the study-group mean minus the control-group mean. The estimate is -0.13. The negative sign reflects that the study-group mean, 0.09, is below the control-group mean, 0.22, on the endpoint scale. This is an unadjusted comparison of group averages. It does not account for covariates through a reported regression model, and the registry does not describe a covariate-adjusted analysis. The estimate is a difference in the endpoint’s units, not a percentage change or a participant-level effect.

What does the standard deviation add?

The study-group standard deviation is 0.04 and the control-group standard deviation is 0.32. A relatively larger standard deviation indicates more spread of observed values around that group’s mean, but it does not identify why values vary or whether a small number of observations account for much of that spread. In general, unequal variability can matter when selecting or assessing methods that assume similar variation between groups. This is a general statistical point; the registry does not report a diagnostic assessment of the endpoint distributions or a variance assumption check.

The reported comparison includes a pooled standard deviation of 0.221 as a standardized comparison input. Pooling combines information about variability from the two groups under a common-variance approach. Given the different group standard deviations, it is useful to keep the raw-scale mean difference and the standardized estimate distinct. The record does not explain the method used for this pooled value or state that a particular standardized effect measure was the prespecified primary analysis.

How should the p-value be read?

The posted unadjusted p-value is 0.027. In general, a p-value describes how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions are appropriate. It is not the probability that the null hypothesis is true, nor is it a measure of effect size or clinical importance. The registry does not report the test used to obtain this p-value. It should therefore be identified as unadjusted, without naming a test or assuming details that are not documented.

In general, an unadjusted result is calculated for a comparison without correcting its p-value or interval for the possibility of multiple statistical tests. Whether multiplicity correction is needed depends on the planned family of hypotheses and the study’s aims. The registry lists three outcome measures and one secondary outcome, but it does not report a multiplicity strategy or a complete analysis plan. It is not possible to determine from the record whether this primary comparison was part of a prespecified testing hierarchy.

What does randomization contribute?

Random assignment is intended to make treatment groups comparable, on average, with respect to characteristics that could affect outcomes. It supports a between-group interpretation, but it does not guarantee balance in a particular trial, ensure that all randomized participants are analyzed, or correct problems in outcome measurement. The registry labels allocation as randomized but does not describe sequence generation, concealment, stratification, or the analysis population. Those design details are not reported in the registry record.

Masking is listed as single, but the identity of the masked party and the masking procedures are not described. Since the primary measure depends on the investigational system, the device’s role in measurement is relevant context. The control group used the device with cuff-pressure control disabled, and the record says carbon dioxide above the cuff was recorded. Further detail on measurement validation, data review, and whether outcome assessment could be influenced by knowledge of assignment is not reported.

How is the endpoint constructed?

The registry describes integrating carbon dioxide level over the duration of leakage to form a patient-level area under the curve, then dividing by the number of hours in the trial. In general, an area-under-the-curve summary combines the level of a quantity with the time over which it is observed. Dividing by time expresses an hourly standardized measure, as specified in the endpoint description. The curve uses adjacent time intervals with valid readings, and the system records carbon dioxide above the cuff every few minutes in clinical mode. The record does not describe how gaps, invalid readings, or incomplete observation periods were handled in the analysis.

There are 34 study participants and 30 control participants in the primary comparison, while enrollment was 76. The registry does not explain the difference. It also does not report whether the endpoint analysis followed intention-to-treat, per-protocol, or another population definition. A reader should not infer the analysis population from the randomization label or from the outcome group sizes alone.

Overall, the numerical comparison can be described as a mean difference with a confidence interval and an unadjusted p-value. The interval method, test, treatment of missing values, and full statistical analysis plan are not reported in the registry record. These omissions do not change the values of the posted comparison, but they limit independent assessment of the assumptions and analytic decisions behind it.

10. Confidence Intervals and Precision

The estimated mean difference is -0.13, with a confidence interval from -0.245 to -0.015. A confidence interval is a range of estimates compatible with the observed data and the method’s assumptions. It conveys uncertainty around the estimated group difference: values closer to either endpoint represent different plausible magnitudes of the mean difference under that method. It is not a range containing a specified proportion of individual participants’ outcomes, and it is not a guarantee that the true value lies within the interval.

Both interval endpoints are negative, so the interval does not include zero. In the direction of the comparison, the compatible values are below zero, indicating a lower mean in the study group than in the control group. The interval also indicates that the estimate is not known with unlimited precision: it spans a range of possible magnitudes. The registry does not report a clinically meaningful threshold against which to judge that range. Statistical precision and practical importance are separate considerations.

The study and control standard deviations are 0.04 and 0.32, respectively. The contrast in dispersion is relevant context for understanding how variable the endpoint was in the observed groups. The registry does not provide enough distributional information to determine the shape of the values or the influence of extreme observations. Nor does it state which interval procedure was used. Interpretation should therefore stay with the posted interval rather than assume particular distributional or modeling details.

The interval is associated with an unadjusted comparison. It does not account for any unreported multiplicity adjustment, covariate adjustment, or missing-data procedure. The comparison uses 34 study participants and 30 control participants, not the enrollment count of 76, and the reason for that difference is not reported. These features matter when judging how broadly to generalize the apparent precision. The interval quantifies uncertainty under the calculation used; it cannot address uncertainty created by undocumented design or analysis choices.

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 planning figures are participants per arm, not total participants and not total events. Each row illustrates a different fraction of the observed effect: 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For each assumed effect, the 80% power column gives the planned number of participants per arm for an 80% chance of detecting that effect under the listed assumptions. The 90% power column gives the corresponding number per arm for a 90% chance. Power is a design probability under a stated model and effect size, not a measure of how well the completed trial performed.

The planning illustration assumes 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. The figures are 46 and 61 participants per arm for planning around 100% of the observed effect; 81 and 108 per arm for 75% of the observed effect; and 182 and 243 per arm for 50% of the observed effect, for 80% and 90% power respectively.

Smaller assumed effects require more participants to detect under the same planning assumptions. This is a general feature of power calculations: a smaller separation between group means is harder to distinguish from sampling variation. These values are planning illustrations based on the observed effect, not the trial’s original sample-size justification. The original design assumptions are not reported in the registry record. The figures are not observed power; they do not measure the probability that the completed study’s result is true or establish whether the study was adequate for its original purpose.

The sample-size curve should be interpreted as another display of the same planning relationship, not as an additional outcome result. No time-to-event endpoint is being used for these figures; the stated convention for this comparison is participants per arm. These calculations also do not explain why the primary outcome comparison contains 34 study participants and 30 control participants when enrollment was 76. Participant flow and the analysis population are not reported.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.130; pooled standard deviation σ = 0.221.
2. n = 2 × (1.96 + 0.842)² × 0.221² / -0.130² = 45.3, rounded up to 46 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
delta <- -0.13                      # observed difference in means
sigma <- 0.220790369121423                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1857986)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 46 (80% power), 61 (90% power)
 75% of observed effect: n per arm = 81 (80% power), 108 (90% power)
 50% of observed effect: n per arm = 182 (80% power), 243 (90% power)
power.t.test: 46.3 
Simulated power at n = 46 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 lists three outcome measures and identifies one secondary outcome: the number of cuff-pressure measurements within the safety accepted range (24 and 40cmH2O). The registry entries described for the primary result include one unadjusted comparison, and the registry reports zero analyses. No complete statistical analysis plan or multiplicity procedure is reported in the registry record. It is therefore not possible to determine whether additional planned comparisons, outcome time points, or subgroup analyses were intended, or whether the primary test was selected from a larger family of analyses.

In general, multiplicity arises when several hypotheses are tested and the chance of at least one misleading positive result can increase if each is assessed separately without a plan for controlling that risk. Adjustments, prespecified hierarchies, and other strategies are possible, but the appropriate approach depends on the study’s aims and protocol. No particular strategy should be attributed to this trial from the available record. The reported p-value is described as unadjusted, and no correction should be assumed.

The registry does not report how missing endpoint observations were handled, whether missingness occurred, or whether values from all randomized participants were included. Enrollment was 76, whereas the primary comparison includes 34 participants in the study group and 30 in the control group. The reason for this difference is not reported. There is no stated imputation method, sensitivity analysis, or comparison of participants with and without endpoint data in the information available.

The analysis population is also not described. The record does not say whether the primary comparison followed intention-to-treat, per-protocol, or another definition, and it does not provide participant flow or reasons for exclusion. Randomized allocation is important context, but it cannot establish how the post-randomization data were analyzed. The registry does not report interim analyses, stopping rules, or subgroup analyses. These absences limit assessment of whether the posted comparison represents a fully prespecified analysis and how robust it may be to missing data or alternative analysis choices.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (9.1%), hemodynamic instability (3.0%).

The registry reports serious adverse events affecting 3 of 39 participants at risk in the study group and 4 of 33 participants at risk in the control group. Other adverse events affected 7 of 39 participants at risk in the study group and 6 of 33 participants at risk in the control group. These are counts of participants recorded as affected, alongside the group-specific numbers at risk; they are not a complete description of event timing, severity beyond the serious/non-serious distinction, or recurrence.

The top serious adverse-event terms listed are Death at 9.1% and Hemodynamic instability at 3.0%. The record does not provide an arm-specific mapping for these terms in the registry record, so they should not be assigned to one group. Death counts by arm are not reported. The percentages should be read as the registry’s listed terms, not recalculated or interpreted as group-specific risks.

These figures are descriptive. They do not establish whether an event was caused by the device or by other aspects of care, and the record does not report an adjusted comparison or uncertainty interval for adverse events. Different numbers of participants were at risk in the two groups. The available information also does not give event-level details or the observation period used for each adverse-event category. The figures should therefore be interpreted as registry-reported counts and terms, not as a definitive comparison of safety.

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

The posted primary result is a lower average value for the device-measured carbon dioxide leakage endpoint in the study group than in the control group. The estimated mean difference is -0.13, and its confidence interval ranges from -0.245 to -0.015. The unadjusted p-value is 0.027. Those statistics describe the observed group comparison and its uncertainty under the analysis represented by the posted numbers.

The result does not establish that every participant in the study group had less leakage than every participant in the control group. Group means summarize distributions, and the registry reports different standard deviations in the two groups. The available record does not show individual values or explain the shape of those distributions. Nor does it report a threshold defining a clinically meaningful change on this endpoint. The statistical comparison alone therefore does not settle the practical significance of the difference.

The endpoint is a patient-level measure based on carbon dioxide readings above the cuff over time, standardized per hour. It addresses the trial’s stated question about leakage around the endotracheal tube cuff. It should not be extended to outcomes not measured by this endpoint. The registry also identifies adverse events as a safety measure and lists a secondary cuff-pressure outcome, but the figures available for those outcomes do not constitute a complete assessment of all possible benefits and harms.

Randomization supports a comparative design, but important details are not reported: the allocation procedure, who was masked, the analysis population, participant flow, and handling of missing endpoint data. Enrollment was 76 while the primary result includes 34 study participants and 30 control participants, and the reason is not reported. The original sample-size assumptions and multiplicity approach are also not reported. These gaps limit how fully the posted comparison can be evaluated.

Accordingly, the defensible interpretation is specific: the registry presents an unadjusted difference in means for a device-measured leakage outcome, with the stated interval and p-value. The result should not be translated into a claim about all aspects of care, an individual patient’s outcome, or a complete safety conclusion. The registry record does not report enough detail to resolve those broader questions.

16. Why This Trial Matters Statistically

This trial illustrates how a device-focused clinical question can depend on a measurement system that is also part of the intervention. The primary endpoint is based on carbon dioxide readings collected by the AnapnoGuard 100 system. The control group was also connected to the unit, with cuff-pressure control disabled, so the comparison concerns the system’s normal clinical mode against a control configuration that retained the measurement device. That design context matters when describing what the contrast represents.

The endpoint also combines level and duration into an area-under-the-curve summary and standardizes it by time. This construction makes the outcome more informative than a simple indication that leakage was present or absent, but it also means that interpretation depends on how valid readings and observation periods are handled. The registry describes adjacent intervals with valid readings but does not report its approach to gaps or incomplete observations. Such measurement details can be important in any repeated-measure setting.

The group summaries show markedly different standard deviations, so the mean difference should be read alongside the variability and not as a complete account of individual responses. The confidence interval adds information about uncertainty in the estimated contrast, while the unadjusted p-value does not express clinical importance. Together, the estimate, spread, and interval offer a more useful statistical description than a binary statement based only on a p-value.

The record also demonstrates why enrollment and outcome analysis counts should be distinguished. Enrollment was 76, but the primary comparison contains 34 and 30 participants in the two arms. Without participant flow and a stated analysis population, readers cannot tell how the outcome sample was formed. Statistical reporting is strongest when these design and analysis details accompany the result; they are not reported in the registry record.

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 primary comparison includes 34 participants in the study group and 30 in the control group, compared with enrollment of 76. The registry does not explain the difference, report participant flow, or define the analysis population. This makes it difficult to assess how outcome availability and exclusions may affect interpretation. Handling of missing endpoint readings and missing participant-level outcomes is not reported.

The trial is labeled randomized and single-masked, but the record does not describe the randomization process, allocation concealment, who was masked, or how masking was maintained. These details matter for assessing the risk of bias and the comparability of groups during conduct and analysis. The primary endpoint depends on the investigational device’s measurement system, and a separate validation method is not described in the record.

The endpoint construction uses readings taken every few minutes and intervals with valid readings, but the registry does not state how gaps, invalid readings, or differing observation durations were treated analytically. The mean and standard deviation are reported, but distributional details are not. The study and control standard deviations differ substantially; no distributional diagnostics or sensitivity analyses are reported.

The posted comparison is unadjusted. The registry does not report the test or confidence-interval method, covariate adjustment, multiplicity handling, or a complete statistical analysis plan. It does not report the original sample-size justification, interim analyses, stopping rules, or subgroup analyses. The planning figures are illustrations based on the observed effect, not evidence of the original design assumptions.

Finally, no clinically meaningful threshold for the primary measure is reported. The available serious and other adverse-event counts are descriptive, and the record does not provide event-level details, arm-specific mapping for the listed serious terms, or uncertainty estimates for safety comparisons. These limitations constrain both the precision of the statistical interpretation and the broader conclusions that can be drawn from the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Evaluating Air Leak Detection in Intubated Patients — NCT01857986.
• Registry record last updated 2017-06-19; status last verified 2017-05.
• Results first posted 2017-06-19.
• 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

NCT01857986, “Evaluating Air Leak Detection in Intubated Patients,” is listed as a completed randomized, single-masked, parallel-group study sponsored by Hospitech Respiration. Enrollment was 76; the study began in 2013-09 and primary completion was 2015-03. The phase is listed as not applicable.

The primary outcome measures carbon dioxide leakage above the endotracheal tube cuff over time, standardized per hour. The posted mean was 0.09 in the study group and 0.22 in the control group, with a mean difference of -0.13, a confidence interval from -0.245 to -0.015, and an unadjusted p-value of 0.027. The comparison includes 34 study participants and 30 control participants; the reason these counts differ from enrollment is not reported in the registry record.

The record lists one secondary outcome and descriptive serious and other adverse-event figures. It does not report the original sample-size justification, analysis population, missing-data approach, multiplicity plan, or several other statistical and design details relevant to interpreting the results.