Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants (NCT03137225), a randomized na study. The primary outcome is Number of Unexpected Events.

2. Clinical Question

The investigator's stated hypothesis is that synchronizing ventilator breaths with the infant's breaths using NAVA will reduce the number and/or severity of apnea, bradycardia and desaturation episodes compared with NIPPV. That is the rationale being tested, not a reported finding. The primary outcome focuses on event counts by ventilation mode; the registry record does not report a numerical comparison or an estimate of the effect.

The planned comparison is within a crossover design: the two ventilation modes are used in different orders, with the sequence randomized. This makes the question a comparison of modes under the study conditions, while also making order and period relevant considerations. The record does not report results that would show whether event patterns differed by mode, whether the modes were experienced in both sequences as planned, or how any period or order effects were handled. Because the outcome results are withheld for confidentiality, the clinical question remains unanswered by the posted results.

3. Trial Design

The study, titled “Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants,” is recorded as a randomized crossover trial. Its two device interventions are neurally adjusted ventilatory assist (NAVA) and nasal intermittent positive pressure ventilation (NIPPV). Randomization concerns the order of the modes: the adverse-event records identify the sequences as NIPPV then NAVA mode and NAVA then NIPPV mode. Masking is recorded as none.

In a crossover design, a participant is intended to receive each treatment or condition in sequence, allowing comparisons across conditions within the same participant. General statistical context: within-participant comparisons can account for stable differences between individuals, but they also require attention to period effects, sequence effects and any carryover from one condition to the next. The registry record does not report how these issues were evaluated or addressed. The study description specifies a one hour stabilization period before the study begins, during which small adjustments to noninvasive settings can be made to clinically optimize settings. It describes continuous, downloadable oxygen-saturation measurement with a pulse oximeter.

The registry record lists enrollment of 1 participant, a start date of 2017-04-15, primary completion on 2017-09-20, and status as terminated. It does not report why the study was terminated. No phase is applicable as recorded. Results for the primary outcome are not reported because only 1 participant was recruited and enrolled and the record states that results are withheld to protect that participant's confidentiality. The record does not report whether the planned crossover procedures were completed, or details of the participant's exposure to the modes. It also does not report a sample-size justification or a statistical analysis plan.

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.

First 4 Hour Measurement Period

Second 4 Hour Measurement Period

Analysis population for the primary outcome, as defined in the registry: Because only 1 participant was recruited and enrolled, results are not reported in order to protect the confidentiality of the participant.

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: Only 1 subject enrolled

6. Primary Endpoint

The registry lists the primary outcome as Number of Unexpected Events, measured over 8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode..

The primary endpoint is titled “Number of Unexpected Events.” It concerns counts of isolated apnea, bradycardia and desaturation events, as well as combined events, compared by ventilation mode. The stated timeframe is 8 hours, from placement on the first study ventilation mode to the end of the second study ventilation mode. The registry record does not specify a unit or a more detailed statistical parameter for this outcome.

Event counts are relevant to the study's stated question because the investigator hypothesizes that synchronizing ventilator breaths with the infant's breaths may change the number and/or severity of these episodes. Counting isolated and combined events can describe how often recorded events occur during the observation period. General statistical context: an event-count endpoint differs from a measure of whether a participant experienced at least one event; counts retain information about repeated events. Interpretation also depends on consistent event definitions and ascertainment across conditions. The registry record does not give further definitions or thresholds for event classification.

The endpoint title should not be read as a reported result. Numerical primary outcome results are not reported, with confidentiality identified as the reason. Nor does the endpoint description supply a numerical estimate of event severity: it specifies counts and categories of events, while the stated hypothesis mentions number and/or severity. The record does not report a separate quantitative severity measure for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a randomized crossover design compare?

The record describes a randomized crossover trial with NAVA and NIPPV as the ventilation modes. The sequence labels in the safety information are NIPPV then NAVA mode and NAVA then NIPPV mode. General statistical context: in a crossover study, the same participant may receive more than one condition in sequence, and the comparison can use measurements from that participant under each condition. Randomizing sequence helps assign the order without choosing it based on a participant's outcome. However, the usefulness of the comparison still depends on the design and analysis accounting for changes over time and possible effects that persist from an earlier condition into a later one.

The registry record does not report the analysis method, any washout approach, or whether period, sequence or carryover effects were assessed. A one hour stabilization period is described before the study begins; the record does not say that this period was intended as a washout between modes. It would therefore be inappropriate to infer that order effects were eliminated or that a particular crossover model was used.

What is an event-count endpoint?

The primary outcome counts isolated apneas, bradycardias and desaturations, and combined events, by ventilation mode. General statistical context: counts record how many events occur, rather than only whether an event occurred. Count data often have a lower bound of zero and may be strongly skewed, particularly when events are uncommon or concentrated in a small number of observation periods. An analysis needs to reflect the outcome's distribution and the way observation time is handled. The registry record does not report a statistical distribution, model, offset, event-rate analysis or other method for analyzing these counts. No such method can be attributed to the trial from the record.

Over-dispersion is a general concern for count data: it occurs when observed variability is greater than a simple count model would expect. If present, it can make model-based uncertainty estimates too small unless the analysis allows for that extra variability. The posted results do not include counts or a model, so over-dispersion cannot be assessed for this study. This is a general methodological consideration, not a finding about the trial.

What would an effect estimate and confidence interval convey?

General statistical context: an effect estimate describes the size and direction of a contrast under a specified analysis. A confidence interval describes the range of values reasonably compatible with the data and method, with its width conveying precision. A narrow interval indicates greater precision than a wide interval, but neither an estimate nor an interval alone establishes whether an effect matters clinically. For this trial, the registry record does not report an effect estimate, confidence interval or p-value for the primary outcome. There is therefore no interval with which to evaluate precision and no reported test result to interpret.

The record's decision not to report results for confidentiality is not the same as reporting an estimate with substantial uncertainty. With no numerical outcome comparison, it is not possible to quantify uncertainty around a contrast. General explanation cannot replace the missing study estimate.

How should planning illustrations be distinguished from trial results?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. It specifies that time-to-event planning uses a total event count, while other planning entries use participants per arm. These are planning assumptions, not evidence that the trial observed a particular effect or had a particular probability of detecting it. The record does not give the numerical planning outputs in the registry record for this analysis, so none can be stated.

General statistical context: a sample-size illustration asks what scale of future study might be needed under specified assumptions. It is not an observed result and should not be described as observed power. A planning calculation based on an observed effect can be especially uncertain when the effect estimate itself comes from very limited data. Here, numerical primary results are withheld, and the record does not report a sample-size justification for the trial's own design. The planning illustration therefore cannot answer the clinical question or provide a substitute for the missing outcome analysis.

What can be learned from the registry analysis entries?

The record lists 0 analyses. That means no analysis results are reported in the registry record; it does not identify which statistical methods were used or establish that no analysis was conducted outside the record. Similarly, the absence of a reported statistical plan is not evidence that a particular method was used. The analysis population, handling of missing observations and method for accounting for the crossover structure are not reported in the registry record. Any interpretation of numerical results would need those details, but the primary results themselves are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary endpoint and secondary outcomes of synchronicity, asynchronicity counts and average pressures. It reports 4 outcome measures and 0 analyses. The primary endpoint itself includes several event categories: isolated apneas, bradycardias and desaturations, as well as combined events. The record notes that the primary outcome has several categories or time points and is not reduced to one comparison. It does not report a multiplicity plan, such as how inference across categories or across primary and secondary outcomes would be controlled or interpreted.

General statistical context: when several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is tested separately without a plan. A prespecified hierarchy or adjustment can help clarify which findings are primary and how multiple comparisons are treated. The registry record does not report such a strategy, so it is not possible to determine how multiplicity would have been handled.

Missing-data methods and the analysis population are not reported in the registry record. There is no numerical primary outcome result available to establish whether observations were missing, how any missing measurements were handled, or which participants or observation periods entered an analysis. The record's stated reason for not reporting outcome results is confidentiality because only 1 participant was recruited and enrolled. This is distinct from a report that outcomes were missing: confidentiality withholding means the registry does not disclose the results, while missing data concern measurements that were not observed or analyzed. The available record does not allow those issues to be separated empirically.

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.

The registry record reports adverse-event information by sequence group. For “NIPPV Then NAVA Mode,” the serious-event figures list 1 at risk and 0 affected; other adverse-event figures list 1 at risk and 0 affected, with 0 deaths. For “NAVA Then NIPPV Mode,” the corresponding figures are 0 at risk and 0 affected for serious events, 0 at risk and 0 affected for other adverse events, and 0 deaths.

These are the counts recorded for the two sequence groups; they should not be read as a comparative safety analysis. The record does not report event descriptions, exposure-specific event rates, statistical comparisons, or additional details about ascertainment. In particular, a zero affected count in a registry entry does not establish that a mode has no risk. The record reports enrollment of 1 participant and withholds outcome results to protect confidentiality, so these sparse safety figures cannot support broad conclusions about safety or differences between ventilation modes.

General statistical context: adverse-event counts are most informative when interpreted alongside the number exposed, duration of exposure, event definitions and completeness of reporting. The record's risk counts and affected counts are reported without combining groups or deriving rates. No further safety interpretation is supported by the registry information.

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

The record identifies a focused clinical question: whether event counts differ between NAVA and NIPPV during noninvasive respiratory support for very low birth weight premature infants. It documents a randomized crossover design, the two ventilation modes, the primary event-count outcome and its 8-hour timeframe. It also identifies secondary outcomes concerning synchronicity, asynchronicity counts and average pressures. These details help define what the study set out to examine.

What the record does not establish is the result of that comparison. The primary results are not reported because only 1 participant was recruited and enrolled, with confidentiality given as the reason. There is no posted effect estimate, confidence interval, p-value or category-specific event count. The record therefore cannot show whether event counts were lower with either mode, whether they were similar, or how precisely any difference was estimated. No claim that NAVA reduces events, or that it does not, follows from the absence of reported results.

The terminated status is recorded, but the reason for termination is not reported in the registry record. It is also not reported whether the participant completed the intended sequence, whether all measurements were collected, or how the crossover structure would be analyzed. The record's adverse-event figures are descriptive entries by sequence and do not supply a comparative safety assessment.

General statistical context: a trial's design and its findings are different kinds of evidence. Randomization and a defined endpoint describe how a comparison was intended to be made; they do not by themselves establish an outcome. To assess a treatment contrast, readers need reported results and enough information to understand the analysis and its uncertainty. Those numerical results are unavailable in this registry record. The trial record is informative about the planned question and the limits on public reporting, but it does not resolve the clinical question.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the gap between a clearly described comparison and an interpretable outcome estimate. The registry record names two ventilation modes, specifies random assignment to sequence, identifies a crossover design and defines an event-count endpoint over an 8-hour period. Those elements make the intended question recognizable. Yet an answer still depends on accessible outcome data and a described analysis.

The record reports enrollment of 1 participant and states that primary results are withheld to protect confidentiality. That decision leaves no disclosed event counts or mode contrast for statistical interpretation. It is not possible to assess effect size, precision, or consistency across event categories. In general, small amounts of data can create substantial uncertainty, but in this case the central limitation is that outcome results are not reported at all; no uncertainty interval is available to quantify.

The crossover structure also highlights why design and analysis details matter. General statistical context: comparisons across periods can be affected by time, sequence and carryover, and a suitable analysis needs to reflect the structure of the observations. The registry record does not report how those factors were handled. It also does not report a multiplicity plan despite listing several outcome categories and secondary measures.

Finally, the registry's planning illustration should be kept separate from the findings. Its stated assumptions describe a planning exercise, not an observed treatment effect or a result from this trial. The record therefore demonstrates why transparent reporting of outcome estimates, analysis choices and limitations is essential: without them, the planned comparison cannot be evaluated as evidence for or against a difference between modes.

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 most consequential trial-specific limitation in the registry record is that the primary outcome results are not reported. The stated reason is protection of participant confidentiality after enrollment of 1 participant. Without numerical event counts or a comparison by mode, there is no estimate of direction, magnitude or precision. This precludes interpretation of the primary endpoint as a treatment contrast.

The record marks the trial as terminated but does not report why it ended or whether the planned crossover sequence was completed. It does not report the analysis population, whether all planned measurements were available, or how missing observations were handled. It also does not report event definitions beyond the categories named in the endpoint description, or a statistical model for the counts.

Several design and analysis details are not reported in the registry record: how period, sequence or carryover effects were assessed; how the multiple event categories and secondary outcomes were handled; and whether there was a prespecified analysis plan. These are relevant to interpreting a crossover comparison and multiple outcomes, but the record does not support assumptions about the methods used.

The safety information is limited to sparse counts by sequence group, without event descriptions or a comparative analysis. The secondary outcomes are listed, but no analysis results are reported. The registry record also does not give a sample-size justification for the trial's own design, or an explanation for termination. These omissions, together with the absence of reported efficacy results, sharply limit what can be concluded from the record. They do not establish that any unreported outcome was favorable, unfavorable or unchanged.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants — NCT03137225.
• Registry record last updated 2019-11-12; status last verified 2019-11.
• Results first posted 2019-11-12.
• 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

NCT03137225 is a randomized, unmasked crossover study of neurally adjusted ventilatory assist (NAVA) and nasal intermittent positive pressure ventilation (NIPPV) in low birthweight premature infants. The registry record lists Virginia Commonwealth University as sponsor, enrollment of 1 participant, a start date of 2017-04-15, primary completion on 2017-09-20, and status as terminated.

The primary endpoint counts isolated and combined apnea, bradycardia and desaturation events across an 8-hour period spanning the first and second ventilation modes. Secondary outcomes include synchronicity, asynchronicity counts and average pressures. The registry record states that primary outcome results are not reported to protect the participant's confidentiality. It does not report the reason for termination, numerical outcome estimates, or the statistical analysis used.