This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effect of Intrathoracic Pressure Regulation on Traumatic Brain Injury (NCT01824589), a randomized phase 4 study. The primary outcome is Intracranial Pressure (ICP).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01824589 |
| Phase | Phase 4 |
| Condition | Head Injury |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Advanced Circulatory Systems |
| Results posted | Yes |
2. Clinical Question
Population
Patients with head injury and elevated intracranial pressure were the intended population in the brief summary. The official title also refers to elevated intracranial pressure due to brain injury or intracranial pathology. The registry record reports an enrollment of 1; it does not provide further participant characteristics.
Intervention
The interventions were devices identified as -7 cm H2O ITPR and -12cm H2O ITPR. The arm descriptions pair these settings with tidal volume settings of 6ml/kg or 8ml/kg, and identify the device used first in each group.
Comparator
The registry describes a randomized crossover model, with four groups reflecting the combinations of device setting and tidal volume setting. It does not report the crossover sequence beyond identifying each group’s first device, or give details about periods between device settings.
Primary question
The primary outcome is intracranial pressure (ICP), measured in mmHg. The record describes comparing ICP during 15 minutes of ITPR use with baseline. The study’s stated purpose also includes examining cerebral perfusion pressure (CPP) and identifying an optimal ventilation tidal volume, but no outcome estimates or analyses are posted.
In general, a crossover study compares conditions within participants over time, rather than relying only on comparisons between separate groups. This can be useful when the measured outcome may be observed repeatedly under different conditions. Interpretation depends on the sequence, timing, and handling of measurements across periods. Those details are not reported in the registry record, so the intended comparison cannot be reconstructed fully.
3. Trial Design
The registry classifies this as a Phase 4, randomized, single-masked, crossover study. It lists an enrollment of 1 and a status of terminated. The record gives a start and primary completion date of 2012-08, but does not explain why the study was terminated or provide further details about its conduct. The sponsor is Advanced Circulatory Systems.
Four group descriptions combine two device settings with two tidal volume settings. Group A is described as using a tidal volume setting of 6ml/kg with the -7cm H2O ITPR as the first device; Group B uses 8ml/kg with the same first device. Group C uses 6ml/kg with the -12cm H2O ITPR first, and Group D uses 8ml/kg with that device first. The registry also lists the device interventions as -7 cm H2O ITPR and -12cm H2O ITPR. The arm descriptions do not establish the complete order in which conditions were administered.
Single masking indicates that the registry records masking, but does not identify who was masked. Details about randomization procedures, allocation concealment, crossover periods, washout, or how treatment sequence was generated are not reported in the registry record. The record does not explain how an enrollment of 1 relates to the four group descriptions. Consequently, the design classification and listed conditions can be described, but the operational details and actual allocation cannot be assessed.
The brief summary frames the study as proof of clinical concept, with a stated aim of assessing changes in CPP and ICP during ITPR use and determining an optimal tidal volume. The primary outcome listing is ICP. Secondary outcomes include CPP, lung compliance, and arterial blood gases (PaCO2). These stated aims and listed measures describe what the study intended to evaluate; they do not establish that those measurements were collected or analyzed.
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
| Stage | Group A | Group B | Group C | Group D |
|---|---|---|---|---|
| STARTED | 1 | 0 | 0 | 0 |
| COMPLETED | 1 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
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.
| Characteristic | Unit | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 1 | 0 | 0 | 0 | 1 | |
| Age, Categorical: <=18 years | participants | 0 | — | — | — | 0 |
| Age, Categorical: Between 18 and 65 years | participants | 0 | — | — | — | 0 |
| Age, Categorical: >=65 years | participants | 1 | — | — | — | 1 |
| Gender: Female | participants | 0 | — | — | — | 0 |
| Gender: Male | participants | 1 | — | — | — | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Intracranial Pressure (ICP), measured over 15 minutes after device is activated.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mmHg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is intracranial pressure (ICP), with the unit recorded as mmHg. The stated timeframe is 15 minutes after the device is activated. The description says that change in ICP from baseline will be compared with ICP during 15 minutes of ITPR use. No numerical ICP value, change estimate, uncertainty interval, or statistical test is reported in the registry record.
In general, an endpoint is a prespecified measure used to address a study question. ICP is the primary measure listed in this record, while the study summary also describes an interest in CPP. These are distinct measures: the record names ICP as primary and lists CPP among the secondary outcomes. That distinction matters when reading the study’s stated goals; the broader rationale does not make CPP the primary endpoint.
In general, a baseline comparison can help describe how a measure changes during an intervention period. A measurement taken at a specified time after activation is only interpretable alongside the definition of baseline, the measurement schedule, and the analysis approach. The registry record does not state how baseline was defined, whether repeated readings were averaged, or how measurements across crossover conditions were handled. It also does not provide endpoint data. The intended measurement is therefore identifiable, but its observed magnitude and precision cannot be judged.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study question and design, but it does not provide a numerical primary-outcome result. It lists ICP as the primary endpoint, specifies mmHg as its unit, and gives a timeframe of 15 minutes after activation. The outcome analysis count is 0, and the record contains no posted estimate of change from baseline, confidence interval, or inferential test. Therefore, there is no reported effect estimate to interpret for ICP.
The study’s stated purpose mentions an increase in CPP and a decrease in ICP, as well as determining an optimal tidal volume. These statements describe the intended questions, not findings. The secondary outcome list includes CPP, lung compliance, and arterial blood gases (PaCO2). The record does not report numerical results for those measures either. No conclusion about the direction or size of any change can be drawn from the stated aims alone.
The enrollment is recorded as 1. That fact, together with the absence of posted analyses, limits what can be said about the evidence available in the registry. The record does not explain whether measurements were obtained, whether data were incomplete, or how the enrollment relates to the four group descriptions. It is not possible to infer a treatment comparison from group labels or intervention descriptions.
In general, an effect estimate describes the observed difference or change, while a confidence interval expresses uncertainty around that estimate under the assumptions of the analysis. Neither is reported for the primary endpoint. Without them, the precision of an estimated effect cannot be evaluated. A p-value, if reported, would address compatibility with a specified statistical model and null hypothesis; it would not by itself describe the size or clinical importance of an effect. No p-value or statistical test is posted in this record.
The study is listed as terminated, but the record does not give a reason. Termination alone does not establish whether data were collected, whether an intervention had an effect, or why analyses are absent. The registry information supports a description of the planned research question and its recorded status, not an efficacy conclusion. Any sample-size illustrations associated with the posted material should be read as planning exercises, not as observed power or as evidence of an outcome.
9. Statistical Methods Explained
Statistical methods can only be evaluated to the extent that the registry record reports them. It classifies the study as randomized, single-masked, and crossover, but does not report a detailed statistical analysis plan. The outcome analysis count is 0. There are no posted effect estimates, uncertainty intervals, p-values, or descriptions of fitted models. The following concepts explain what would generally matter for interpreting a study of this kind; they are not claims about methods used in this trial.
What does a crossover design compare?
In general, a crossover design measures participants under more than one condition, so that a participant can contribute measurements under different treatment settings. Such designs can reduce the influence of stable differences between participants when the same people are observed across conditions. This benefit depends on valid comparisons across periods and on appropriate handling of time, sequence, and repeated observations.
The registry record identifies the model as crossover and lists the first device for each group. It does not describe the full sequence, duration of each condition, interval between conditions, or any washout procedure. Without those details, readers cannot assess whether carryover from an earlier condition was considered or whether period effects were separated from device effects. The record also does not state how measurements from a participant would be combined or compared across conditions.
Why does randomization matter?
In general, random assignment is intended to reduce systematic differences between conditions by making allocation independent of participant characteristics in expectation. The quality of that protection depends on how the random sequence was generated and implemented. The record says the study was randomized, but the sequence-generation and allocation procedures are not reported. The group descriptions alone do not show how participants were allocated or whether the intended allocation occurred.
What can masking establish?
In general, masking can limit the influence of knowledge about treatment assignment on care, measurement, or assessment. The record classifies the study as single-masked, but does not say which people were masked or how masking was maintained. This is especially relevant to interpreting measured outcomes because the potential for assessment-related influence depends on who knew the condition and how measurements were obtained. These procedural details are not reported in the registry record.
How should uncertainty be read?
In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method and assumptions. Its width conveys precision: a wider interval indicates less precision than a narrower interval. A point estimate without an interval can conceal substantial uncertainty, while an interval does not resolve problems such as bias, incomplete follow-up, or an unsuitable analysis model. No confidence interval or point estimate for ICP is reported, so neither magnitude nor precision can be assessed.
In general, a p-value measures how unusual the observed data would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A p-value must be interpreted alongside the estimated effect, uncertainty, design, and analysis plan. The registry record reports no p-value or test for the primary outcome.
Why can repeated measurements need special handling?
In general, measurements from the same participant are correlated rather than independent. An analysis that treats repeated observations as unrelated can misstate uncertainty. Crossover analyses may need to account for participant-level variation, treatment condition, period, and sequence, depending on the design and collected data. The registry record does not report the planned model or whether repeated measurements were collected, so it is not possible to determine how these issues were addressed.
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If present, it can make standard errors and intervals too small unless the analysis accounts for the extra variation. Whether over-dispersion is relevant depends on the outcome type and data structure. The registry lists ICP as a number but does not provide its distribution or any model, so no claim about over-dispersion in this study is possible.
What is the role of planning calculations?
In general, sample-size calculations use assumptions about the effect to detect, variability, significance level, allocation, and analysis method. They are planning illustrations, not measures of the evidence produced by a completed or terminated trial. A calculation based on an observed effect is especially dependent on that effect estimate and should not be described as observed power. The registry record does not report its own sample-size justification or statistical planning assumptions. Any planning illustration should therefore be kept separate from the trial’s absent outcome analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome of ICP and secondary outcomes of CPP, lung compliance, and arterial blood gases (PaCO2). It also records four outcome measures, but provides no outcome analyses. The registry record does not report whether a multiplicity adjustment was planned, how primary and secondary comparisons were prioritized in the analysis, or whether particular time points or device settings formed separate tests.
In general, testing several outcomes or comparisons can increase the chance of obtaining an apparently unusual result by chance if each is assessed independently. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers understand how multiple tests were handled. No such procedure is reported. There are no posted p-values or estimates against which to assess any multiplicity strategy.
The record does not report a missing-data plan, reasons for missing measurements, or how incomplete observations would be handled. It also does not define an analysis population, such as whether analysis would follow assigned conditions or include only participants with measurements under specified conditions. These omissions do not prove that data were missing or that a particular analysis set was used; they mean these details are not reported in the registry record.
In general, missingness can affect both the amount of information available and the validity of comparisons, depending on why observations are absent. A complete-case analysis, imputation method, or model using available repeated measurements relies on different assumptions. Without a description of the data collected and the analysis plan, the impact of missing data cannot be evaluated. The record’s terminated status does not establish whether missingness occurred or explain the absence of analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group A | 0 | 1 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group A | 0 of 1 |
| Group B | 0 of 0 |
| Group C | 0 of 0 |
| Group D | 0 of 0 |
The adverse-event record gives group-level figures for serious and other adverse events, with separate counts at risk and affected. For Group A, the record lists 1 at risk for serious events and 0 affected; it also lists 1 at risk for other events and 0 affected. For Groups B, C, and D, the at-risk and affected counts shown for both categories are 0. Deaths are recorded as null for each group, which means the registry record does not report those values.
These entries should not be read as a complete safety assessment. The registry record does not provide event descriptions, follow-up duration, severity details beyond the serious/other categories, or an explanation of the zero at-risk entries for Groups B through D. A zero at risk is not the same as observed absence of events among participants under that condition. The record lists no serious event terms. It does not provide enough information to assess whether safety events were systematically collected across the intended crossover conditions.
In general, adverse-event counts are most informative when the population monitored, observation period, event definitions, and completeness of reporting are clear. Here, no broader safety conclusion can be drawn from the recorded counts alone. The missing death values should not be interpreted as zero deaths.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, single-masked crossover study was registered to examine intrathoracic pressure regulation therapy in the context of elevated ICP. It identifies ICP as the primary outcome and describes comparison with baseline during 15 minutes of ITPR use. It also lists CPP, lung compliance, and arterial blood gases (PaCO2) as secondary outcomes, and gives device and tidal-volume settings in four group descriptions.
It does not establish what happened to ICP or any secondary outcome. No numerical outcome results, effect estimates, confidence intervals, or statistical tests are posted. The study’s stated aim to increase CPP, decrease ICP, and determine an optimal tidal volume is not a report of observed findings. The record therefore cannot show the direction, magnitude, or precision of an outcome change.
The enrollment is recorded as 1, and the status is terminated. The registry does not explain the relationship between the enrollment and four group descriptions, why the study ended, or whether measurements were collected. Those details should not be filled in by inference. In particular, the absent analyses cannot be treated as evidence that the intervention had no effect, nor as evidence that it had an effect.
In general, a clinical result is interpreted using the observed estimate, its uncertainty, the quality of the design and data, and the relevance of the measured outcome. When those estimates are unavailable, the appropriate conclusion is limited to what the record documents: a study question, a registered design, and an endpoint definition. This record does not support a conclusion about treatment efficacy, safety, or the best tidal volume.
Any sample-size calculations are planning illustrations rather than observed power. They cannot substitute for outcome data or resolve uncertainty about the study’s conduct. The registry record is most useful for identifying the intended comparison and for making clear that interpretable outcome analyses are not reported.
13. Why This Trial Matters Statistically
This study illustrates why a registered research question and a reported result are not the same thing. The record states a specific physiological aim and identifies ICP as the primary endpoint, but it does not provide the outcome analysis needed to quantify what was observed. For statistical interpretation, the absence of an estimate and its uncertainty is decisive: neither the size nor precision of a result can be evaluated.
The crossover classification also highlights the importance of design details. In general, within-participant comparisons can account for stable differences between participants, but their interpretation relies on sequence, period, and carryover considerations. The registry identifies the first device in each group but does not report the full sequence or analysis approach. Readers therefore cannot assess how the planned crossover comparisons would be separated from effects of time or order.
The record further demonstrates the value of distinguishing stated aims from outcome findings. The summary describes goals involving CPP, ICP, and tidal volume, while the outcome listing identifies ICP as primary and names other measures as secondary. Keeping these roles distinct helps prevent a study objective from being mistaken for an observed result. With no posted analyses, none of these outcomes can be interpreted as demonstrating a direction or magnitude of change.
Finally, safety counts require context about who was monitored and how completely events were collected. At-risk entries of zero for some groups and unreported death values limit interpretation. The record can be read accurately only by preserving those distinctions rather than treating missing or inapplicable entries as reassuring evidence. Statistically, this is a case where transparency about what is not reported is as important as describing the design that was registered.
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.
Several limitations specific to this record constrain interpretation. The registry reports an enrollment of 1, while the arm descriptions list four groups. It does not explain how that enrollment relates to those groups, whether all group conditions were reached, or whether the group descriptions reflect intended rather than completed treatment sequences. No inference about actual allocation or data collection is warranted.
The status is terminated, but no reason for termination is reported. The registry gives start and primary completion dates of 2012-08, without explaining the study’s progress or whether the planned endpoint was measured. Outcome analysis count is 0, and the record does not post ICP or secondary-outcome results. Thus, neither the completeness of the outcome record nor the reason for the lack of analyses can be determined.
Although the design is classified as randomized, single-masked, and crossover, important operational and statistical details are absent. The registry does not describe sequence generation, allocation procedures, the identity of masked parties, the full crossover sequence, intervals between conditions, baseline definition, or analytic handling of repeated measurements. The study’s sample-size justification, interim analyses, and statistical plan are also not reported in the registry record.
The adverse-event entries are limited: the record lists no affected participants in the categories shown, includes zero at-risk entries for several groups, and does not report death counts. Event collection methods and follow-up are not described. These features prevent a broad safety interpretation. Overall, the record allows description of the registered question and design, but not assessment of efficacy, precision, analysis validity, or safety completeness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Intrathoracic Pressure Regulation on Traumatic Brain Injury — NCT01824589.
- Registry record last updated 2015-02-16; status last verified 2015-02.
- Results first posted 2015-02-16.
- 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.
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18. Record Summary
The record concerns NCT01824589, titled “Effect of Intrathoracic Pressure Regulation on Traumatic Brain Injury.” It describes a Phase 4 randomized, single-masked crossover study, sponsored by Advanced Circulatory Systems, with an enrollment of 1 and status listed as terminated.
The primary outcome is ICP in mmHg, assessed 15 minutes after device activation and described as a comparison with baseline. The listed ITPR settings are -7 cm H2O and -12cm H2O, paired in group descriptions with tidal volume settings of 6ml/kg and 8ml/kg. Secondary outcomes are CPP, lung compliance, and arterial blood gases (PaCO2).
No outcome analyses or numerical results are reported in the registry record. The record does not state why the study was terminated, explain the enrollment in relation to the group descriptions, or provide a statistical analysis plan.