Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) and Laser Laryngeal Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) and Laser Laryngeal Surgery (NCT03086265), a randomized na study. The primary outcome is Lowest Intraoperative Peripheral Oxygen Saturation (SpO2).

2. Clinical Question

The study addresses a procedural question: whether laser laryngeal surgery can be conducted with respiratory support that does not use a tracheal tube, while monitoring oxygen saturation and other outcomes. The registry describes the intended approach as completely tubeless, but also lists jet ventilation as a secondary outcome. That distinction matters when reading the results: the intervention was THRIVE, while the need for jet ventilation was tracked separately as an outcome.

The primary endpoint is a measure of oxygen saturation during surgery, not a direct measure of every aspect of gas exchange or procedural success. Other listed outcomes include time to spontaneous ventilation, apnea time, anesthesia duration, anesthetic and vasoactive drug doses, and the count of participants requiring jet ventilation. The registry does not report detailed eligibility criteria, baseline participant characteristics, or the exact surgical case mix. The clinical question should therefore be understood within the registry’s stated setting of laser laryngeal surgery, rather than generalized to other procedures or populations.

3. Trial Design

The registry describes a randomized, double-masked, parallel-group trial with an enrollment of 20. The two groups were THRIVE and endotracheal tube, with 10 participants in each group in the posted primary outcome results. The trial is listed as completed. Its phase is listed as not applicable. Stanford University is named as the sponsor.

The study began on 2017-03-24, and primary completion is recorded as 2019-02-26. The registry’s stated purpose was to investigate whether laser laryngeal surgery could be performed safely and potentially more effectively without tracheal intubation or jet ventilation, using high-flow oxygen through a specialized nasal cannula. That statement describes the research aim; it is not itself a result.

Random allocation means that assignment to the two groups was intended to be determined by chance. A parallel design means participants were assigned to one group rather than receiving both approaches as a crossover. The record identifies the trial as double-masked, but which people were masked and how masking was maintained are not reported in the registry record. The randomization procedure, allocation concealment, trial protocol, and detailed eligibility criteria are also not reported in the registry record.

The registry lists 28 outcome measures and 20 analyses, with 15 secondary outcomes posted. The primary endpoint is the lowest intraoperative peripheral oxygen saturation during surgery, summarized as a mean and standard deviation for each group. The posted results include selected secondary measures and adverse-event counts. The planned sample-size justification, intended power, analysis populations, interim analyses, and detailed statistical analysis plan are not reported in the registry record. Consequently, the enrollment should be read as the number recorded for this trial, not as evidence that the study was sized to answer every outcome precisely.

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 Lowest Intraoperative Peripheral Oxygen Saturation (SpO2), measured over Duration of surgery (average approximately 1 hour).

The primary endpoint is the lowest intraoperative peripheral oxygen saturation, or SpO2, during the duration of surgery. The registry describes this measure as an estimate of the amount of oxygen in the blood and gives the timeframe as the duration of surgery, with an average of approximately 1 hour. The result is summarized as a group mean with a standard deviation.

Using the lowest value focuses on the minimum saturation recorded during the procedure rather than an average across the whole operation. In general, a minimum can capture a transient low reading that an overall average might conceal. It is still a measure of peripheral oxygen saturation, not a complete description of respiratory status, and its interpretation depends on how measurements were collected and handled. Those measurement details are not reported in the registry record.

The endpoint is relevant to the stated comparison because the study investigates oxygen support during surgery without a tracheal tube. However, a similar group mean for the lowest saturation does not by itself establish that the two approaches are equivalent, nor does it answer every safety or effectiveness question. The measure is one outcome in a small randomized comparison. The registry does not report a prespecified equivalence or non-inferiority margin, or a threshold defining a clinically important difference. Without those details, the result is best read as an estimate of the observed group contrast and its uncertainty, rather than as a formal demonstration of equivalence.

7. Results Posted in the Registry

• Endotracheal Tube: mean 97.00 versus 97.00 on control; difference 0.00 (95% CI -2.23 to 2.23), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Count of Participants Requiring Jet Ventilation

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Endotracheal Tube: 0.0% (0/10) versus 70.0% (7/10) on control; risk difference -70.0 percentage points (95% CI -98.4 to -41.6); unadjusted two-proportion z-test p = 0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Endotracheal Tube than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to Spontaneous Ventilation

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Endotracheal Tube: mean 11.00 versus 5.00 on control; difference 6.00 (95% CI 2.03 to 9.97), standardized effect d = 1.33; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Endotracheal Tube than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Apnea Time

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Endotracheal Tube: mean 87.00 versus 70.00 on control; difference 17.00 (95% CI -17.44 to 51.44), standardized effect d = 0.43; z-test p = 0.333.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Endotracheal Tube and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the scope beyond the primary oxygen-saturation measure. They cover the need for jet ventilation, timing of spontaneous ventilation and apnea, anesthesia duration, anesthetic doses, and vasoactive drug doses. The registry lists 28 outcome measures, 20 analyses, and 15 posted secondary outcomes. The pattern across the available secondary results is not a single uniformly consistent signal: the endpoints concern different aspects of the procedure and have different measurement scales and precision.

The available secondary results do not overturn or replace the primary result. The primary endpoint addresses the lowest recorded intraoperative oxygen saturation, whereas the secondary measures address procedural support and timing. Similar primary group means can coexist with differences in a secondary measure because the endpoints ask different questions. Conversely, a secondary contrast does not establish a difference in the primary endpoint or resolve the broader study question.

Unadjusted secondary results carry less weight as confirmatory evidence when many outcomes are examined. In general, testing multiple outcomes increases the chance of finding at least one apparently notable result by chance. A prespecified hierarchy or multiplicity procedure can help define how such results should be interpreted, but neither is reported in the registry record. The registry also does not report which secondary outcomes were designated as confirmatory in a protocol or analysis plan.

Accordingly, secondary estimates are best treated as descriptive and hypothesis-generating in this record. Their interpretation should account for the number of outcomes listed, the fact that only 15 are posted, the small enrollment, and the absence of reported adjustment details. They may identify topics for further study, but they do not provide a substitute for a prespecified analysis with clearly reported methods and adequate precision.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Count of Participants Requiring Jet Ventilation
• Time to Spontaneous Ventilation
• Apnea Time
• Duration of Anesthesia
• Total Propofol Dose (Anesthetic)
• Total Remifentanil Dose (Anesthetic)
• Total Phenylephrine Dose (Vasoactive Drug)
• Total Ephedrine Dose (Vasoactive Drug)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry summarizes the primary endpoint as a mean and standard deviation in each group. It also reports a two-sided t-test for the primary comparison. The comparison is between randomized groups, and the posted group sizes are 10 in each arm. A simple unadjusted re-calculation uses the group means and standard deviations to estimate the difference between the group means and its uncertainty; it is not a substitute for an analysis based on individual participant data.

What does a mean difference describe?

For a continuous outcome, a mean difference expresses the contrast between the average values in two groups. Here, the observed group means for lowest intraoperative oxygen saturation are both 97.0, so the re-calculated mean difference is 0.0. The standard deviation describes variation among individual observations within a group; it is not the same as the uncertainty around the group mean. In general, a standard deviation is about the spread of participant values, whereas a standard error or confidence interval describes uncertainty in an estimated quantity.

Why use a t-test?

A t-test is a method for comparing means. The registry identifies the reported method as a two-sided t-test. In general, a two-sided test assesses evidence for a difference in either direction rather than specifying only one direction. A p-value describes how unusual data at least as incompatible with a stated no-difference model would be under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The assumptions and implementation details of the registry’s test, beyond its label, are not reported in the registry record.

The unadjusted p-value of 1.0 is from a simple re-calculation using the posted summary statistics. The registry reports 0.793 for its own two-sided t-test. The registry record does not provide enough detail to identify the reason for this difference. The record does not mark a discrepancy, but that does not supply an explanation for the distinct p-values. Neither p-value should be interpreted as proof that the groups are identical.

What do intervals add?

The re-calculated mean-difference interval for the primary outcome runs from -2.235 to 2.235. An interval conveys a range of effect estimates compatible with the data under a particular calculation method. In general, an interval is more informative than a p-value alone because it shows the direction and scale of estimates consistent with the data. The confidence level and exact interval method are not reported in the registry record, so the interval should be described as posted rather than assigned an unreported coverage level. Its inclusion of zero means that a zero contrast is among the values within the interval; it does not prove that the true contrast is zero.

How are binary and other continuous outcomes handled?

The count of participants requiring jet ventilation is a binary outcome at the participant level: each participant either required it or did not, as recorded. The posted group counts are 7 of 10 for THRIVE and 0 of 10 for endotracheal tube. The re-calculated contrast is expressed as a risk difference, with a negative value because the endotracheal-tube group had fewer recorded participants with the outcome. In general, risk differences describe an absolute contrast in outcome frequency between groups; they are not the same as relative risks.

Time to spontaneous ventilation and apnea time are continuous outcomes summarized by means and standard deviations. For these outcomes the registry reports t-tests, and the posted unadjusted re-calculations report mean differences and intervals. The comparison orientation follows the endotracheal-tube group relative to THRIVE. A positive mean difference on those results means the endotracheal-tube group had the higher mean; a negative value would mean it had the lower mean. This direction convention does not imply that either direction is beneficial.

What are the planning illustrations?

The planning illustrations for selected secondary continuous outcomes are calculations based on the observed effect, not the trial’s original design or observed power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set to a stated fraction of the observed effect. For time to spontaneous ventilation, the illustrations give participants per arm for 80% and 90% power when planning for 100%, 75%, and 50% of the observed effect. The same types of illustrations are given for apnea time. In general, smaller effects require larger samples for a given power under an assumed model. These figures are planning aids only; the original sample-size justification and design assumptions are not reported in the registry record.

Why do secondary tests need caution?

When many outcomes are examined, the chance of at least one apparently notable result can increase. In general, multiplicity methods may control that risk, but the choice depends on which outcomes and comparisons were planned and how they were prioritized. The registry lists 28 outcome measures and 20 analyses, and 15 secondary outcomes are posted. A multiplicity adjustment, a prespecified outcome hierarchy, and a detailed analysis plan are not reported in the registry record. Therefore, unadjusted secondary p-values should be read as descriptive evidence for their individual comparisons rather than as a familywise confirmatory conclusion.

11. Confidence Intervals and Precision

The primary group means are both 97.0, with standard deviations of 2.0 for THRIVE and 3.0 for endotracheal tube. The simple unadjusted re-calculation gives a mean difference of 0.0 and an interval from -2.235 to 2.235. This interval communicates that the estimated contrast is not pinned down to exactly zero, even though the displayed means match. The range includes contrasts in both directions.

In general, an interval’s width reflects both the variability in the data and the amount of information available. With 10 participants in each group, the estimate is based on a limited number of observations. The interval therefore matters alongside the point estimate: a mean difference of 0.0 is the center of the re-calculation, but the interval indicates uncertainty around that center. The registry record does not report the confidence level or full interval method, so it is not appropriate to attach an unreported confidence percentage to these limits.

The interval should not be used as an equivalence test. Equivalence requires a prespecified range of differences considered sufficiently small, together with an analysis designed to assess whether the uncertainty falls within that range. A non-inferiority question likewise requires a prespecified margin and an appropriate analysis. Neither margin nor such a design is reported in the registry record. Thus the posted interval can describe precision, but it cannot answer those formal questions by itself.

The same caution applies to the secondary outcomes. Their intervals vary in width, reflecting differing observed variability and endpoint data. The small enrollment also limits precision for outcomes based on participant counts. These considerations do not invalidate the estimates; they define how narrowly or broadly the results can be read. The primary interval is most appropriately understood as an estimate of uncertainty around the group contrast, not as a guarantee that all values within its limits are equally likely or clinically equivalent.

12. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a two-sided t-test with p-value 0.793. A simple unadjusted re-calculation from the posted group means and standard deviations gives a mean difference of 0.0, an interval from -2.235 to 2.235, and p-value 1.0. The registry record does not explain why the reported and re-calculated p-values differ. It does not provide the individual participant data or fuller test details needed to investigate the difference.

The reported p-value and the re-calculated result are not interchangeable descriptions of the same calculation: one is the registry’s reported analysis, while the other is a simple calculation from summary statistics. The re-calculation does not replace the sponsor’s analysis. Since the record does not identify a discrepancy, there is no stated discrepancy for which to give the sponsor analysis precedence under the posted record’s own discrepancy flag. The difference should be noted without guessing at its cause.

For selected secondary continuous outcomes, the record also reports sponsor t-test p-values alongside unadjusted re-calculations. The registry does not explain the differences between those results either. The p-values should be read with their associated estimates, the small group sizes, and the missing details about the analysis plan. A p-value alone does not convey the size or precision of an effect.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 28 outcome measures, 20 analyses, and 15 posted secondary outcomes. When several outcomes are assessed, multiplicity is relevant because the chance of at least one small p-value can rise across a collection of tests. In general, adjustment procedures or a prespecified testing hierarchy can help control how evidence is judged across multiple outcomes. The registry record does not report a multiplicity adjustment, an outcome hierarchy, or which analyses were designated as confirmatory.

Missing-data handling is not reported in the registry record. The posted primary outcome groups each include 10 participants, but the record does not state whether any measurements were missing, how missing values were handled, or whether all randomized participants were included in the analysis. The analysis population is not reported in the registry record; it is therefore not possible to establish from the posted results whether the analysis followed an intention-to-treat, per-protocol, or another defined population.

The registry also does not report the protocol, detailed statistical analysis plan, planned interim analyses, or the trial’s sample-size justification. The planning illustrations attached to selected secondary outcomes are based on observed effects and stated assumptions; they are not evidence of the trial’s original design or observed power. These omissions constrain assessment of whether the reported analyses followed prespecified decisions, whether any outcomes were selectively omitted, and how much confidence to place in exploratory findings.

In general, a transparent account of prespecification, missingness, analysis populations, and multiplicity helps distinguish confirmatory analyses from exploratory ones. Because those details are not reported in the registry record, the posted p-values and intervals should be interpreted as results for the listed analyses, without assuming unreported safeguards or procedures.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry reports 10 participants at risk for serious adverse events in each group, with zero serious adverse events in both groups. It also reports 10 participants at risk for other adverse events in each group, with zero other adverse events in both groups. Deaths are recorded as zero in each group, and no serious adverse-event terms are listed.

These are counts recorded in the registry, not proof that the approaches have no risk. With 10 participants per group, the record contains limited information about uncommon events. In general, observing no events in a study does not establish that an event cannot occur, particularly when the number of participants is small. The registry does not report detailed adverse-event definitions, collection procedures, severity criteria beyond the serious/other categories, or the period of follow-up for safety reporting. The figures should therefore be read as the reported event counts for this trial, not as a comprehensive safety comparison.

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

The primary result describes the observed group means for the lowest intraoperative peripheral oxygen saturation and an estimate of uncertainty around their contrast. Both group means are 97.0, and the simple unadjusted re-calculation places the mean difference at 0.0. The interval from -2.235 to 2.235 shows that the data do not identify the contrast with great precision. The sponsor’s reported test has a different p-value, and the registry does not explain the difference.

These findings do not establish that the two approaches are equivalent. Equivalence is a specific statistical claim that requires a prespecified margin and an analysis intended to show that the difference lies within that margin; neither is reported in the registry record. The result also does not prove that no difference exists. A nonsignificant or large p-value is not evidence that the true effect is exactly zero.

The endpoint is limited to the lowest recorded peripheral oxygen saturation during the procedure. It does not capture every dimension of gas exchange, procedural performance, recovery, or safety. The secondary measures provide additional observations, but they are subject to their own uncertainty and are not reported with a multiplicity plan. The zero adverse-event counts likewise do not establish an absence of risk.

The trial enrolled 20 participants, with 10 in each primary outcome group. The registry does not report a sample-size justification, planned power, detailed analysis populations, or missing-data methods. Those omissions, together with the limited enrollment and incomplete reporting of methods, restrict how broadly the results can be interpreted. The findings apply to the comparisons and outcomes recorded for this laser laryngeal surgery trial; the registry does not establish how they generalize to other settings or populations.

16. Why This Trial Matters Statistically

This trial is statistically useful because it illustrates why a point estimate, uncertainty interval, and test result answer different questions. The observed primary group means are equal at the displayed precision, but the interval around their contrast remains broad enough to include values in either direction. The result is therefore more informative when read as an estimate with uncertainty than as a simple declaration of no difference.

It also shows why the registry’s reported analysis and a re-calculation from summary statistics should be distinguished. The sponsor’s two-sided t-test p-value is 0.793, while the simple re-calculation gives 1.0. The registry does not explain the difference. Comparing these results encourages attention to analysis details rather than treating a p-value as a self-explanatory fact.

The secondary outcomes highlight a separate statistical issue: a trial can report multiple outcomes that measure different things, while the evidence supporting each varies in precision. Without a reported multiplicity plan or outcome hierarchy, secondary p-values are less persuasive as confirmatory evidence. Planning illustrations based on observed effects can help describe sample-size implications under stated assumptions, but they do not reveal the trial’s original design or prove that its enrollment was adequate.

Finally, zero recorded adverse events in a small study are counts, not proof of no risk. Taken together, the trial offers a focused example of interpreting randomized comparisons while keeping uncertainty, analysis reporting, multiple outcomes, and limited safety information in view.

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 trial enrolled 20 participants, with 10 in each group in the primary results. This limited enrollment constrains precision and the ability to characterize uncommon outcomes. The registry record does not report a sample-size justification or the intended power for the primary endpoint, so it is not possible to determine whether the enrollment was planned to detect a particular difference.

Important design and analysis details are not reported in the registry record. These include the randomization procedure, allocation concealment, which people were masked, how masking was maintained, participant eligibility criteria, baseline characteristics, analysis populations, missing-data handling, and the statistical analysis plan. Interim analyses are also not reported in the registry record. Without these details, assessment of potential bias and fidelity to prespecified analyses is limited.

The primary interval’s confidence level and exact method are not reported. The registry reports a sponsor p-value that differs from the simple unadjusted re-calculation, but provides no explanation. For secondary outcomes, multiple measures are listed and only 15 secondary outcomes are posted; a multiplicity adjustment or testing hierarchy is not reported. The secondary estimates should therefore be interpreted cautiously.

The registry describes the primary endpoint as the lowest intraoperative peripheral oxygen saturation but does not report detailed measurement procedures. It does not report a clinically important difference threshold, an equivalence margin, or a non-inferiority margin. Adverse-event counts are reported, but event definitions, ascertainment details, and safety follow-up are not reported in the registry record. These limitations restrict conclusions about both the clinical meaning and generalizability of the results.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) and Laser Laryngeal Surgery — NCT03086265.
• Registry record last updated 2020-03-17; status last verified 2020-03.
• Results first posted 2020-03-17.
• 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

NCT03086265 is a completed, randomized, double-masked, parallel-group trial sponsored by Stanford University. It compared THRIVE with endotracheal tube during laser laryngeal surgery and enrolled 20 participants. The primary endpoint was the lowest intraoperative peripheral oxygen saturation during surgery.

The posted primary group means were 97.0 in each group. A simple unadjusted re-calculation gives a mean difference of 0.0, with an interval from -2.235 to 2.235; the registry reports a two-sided t-test p-value of 0.793. Selected secondary outcomes and adverse-event counts are also recorded. The registry does not report several design and analysis details needed to assess prespecification, missing data, multiplicity, or the intended precision of the trial.