Hemodynamics and Extravascular Lung Water in Acute Lung Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hemodynamics and Extravascular Lung Water in Acute Lung Injury (NCT00624650), a randomized phase 2 study. The primary outcome is The Primary Efficacy Variable Will be the Total Reduction in Measured Lung Water.

2. Clinical Question

The trial asks whether a treatment strategy directed at extravascular lung water (EVLW) changes measured lung water during treatment of acute lung injury, compared with Modified FACTT management. The primary efficacy variable is described as the total reduction in measured lung water over the first seven days of treatment. The registry record does not report an analyzed result for that endpoint.

The registry lists this as a prospective randomized controlled multicenter trial. It does not report the number of participating centers, the details of eligibility criteria, or participant-level baseline characteristics. Those omissions limit how precisely the intended population can be described.

3. Trial Design

The registry record describes a randomized, parallel-group phase 2 trial of treatment strategies for acute lung injury. It lists single masking, but does not identify who was masked or explain how masking was maintained. The record lists Oregon Health and Science University as the sponsor and reports an enrollment of 33. The start date is 2008-02, primary completion is 2011-01, and the status is completed.

The comparison was between an EVLW-guided algorithm and Modified FACTT management. In the EVLW arm, the registry description says treatment began when EVLW exceeded 9 ml/kg PBW and continued until EVLW was at or below 9 ml/kg PBW or extubation, whichever came first, as tolerated. It describes furosemide and volume contraction when sufficient volumetric preload was available. The control description refers to conservative fluid management based on the protocol used in the FACTT trial. The registry text for this arm is incomplete, so the full treatment rules cannot be reconstructed.

The listed interventions include diuresis with furosemide, fluid boluses using crystalloid or albumin, vasopressors, dobutamine, and concentrating drips and nutrition. The intervention list alone does not establish which treatments each participant received, when they were used, or how frequently protocols were followed.

The primary efficacy variable is total reduction in measured lung water during the first seven days of treatment. Although one outcome measure is listed, the registry record does not contain an analyzed endpoint result. It states that the principal investigator departed before analyses were conducted, that OHSU will not complete analyses for the study, and that the study device is no longer manufactured. The number of analysis entries is zero. Thus, the record describes the planned comparison but does not provide an efficacy estimate or a statistical test of the primary question.

The registry does not report a sample-size justification, the planned statistical model, or details of the randomization procedure. The total enrollment is not evidence by itself of the study's intended precision or of whether the trial achieved its planned enrollment.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The study's Principal Investigator departed the institution before analyses were conducted. OHSU will never have analyses complete for this study. The study device is no longer manufactured.

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 The Primary Efficacy Variable Will be the Total Reduction in Measured Lung Water, measured over The first seven days of treatment.

The primary efficacy variable is described as the total reduction in measured lung water during the first seven days of treatment. This endpoint is intended to capture change in lung water over a defined treatment period, rather than a single measurement at one time. The registry describes the intervention as targeting EVLW, so measured lung water is directly related to the strategy being evaluated.

As a general statistical concept, a change endpoint can summarize how an outcome shifts between a starting point and later measurement or measurements. Its interpretation depends on how the starting value, subsequent measurements, and total reduction are defined. The registry record does not report those operational details, a measurement unit for the primary variable, or how repeated measurements were combined. It also does not provide the endpoint values by arm or an estimated between-arm contrast.

The specified timeframe is the first seven days of treatment. A treatment-window endpoint can focus attention on the period when the intervention is being applied, but it does not on its own describe outcomes after that period. The registry record does not report an analyzed estimate for total reduction in measured lung water, its uncertainty, or a test comparing the treatment strategies. Consequently, the endpoint is described as a planned measure, not as a reported finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the trial as randomized, single-masked, and parallel-group. It does not report the allocation sequence method, concealment procedures, who was masked, or whether masking was successful. The statistical concepts below are general explanations; the registry record does not establish that a particular method was used in this study.

What does randomization contribute?

General: Randomization assigns participants to study groups by chance. When implemented and maintained appropriately, it can reduce systematic differences in prognostic characteristics at the start of a trial. It does not guarantee that groups will be identical, particularly in a small study, and it does not remove the need to describe baseline characteristics, follow-up, adherence, and the analysis population. The registry identifies randomized allocation but does not report the procedure or baseline characteristics needed to assess these features.

What does a parallel-group comparison mean?

General: In a parallel-group design, participants are assigned to a treatment strategy and outcomes are compared across the groups. The registry names EVLW and Modified FACTT management as the arms. It does not report whether the primary endpoint analysis was intended to compare change within each arm, contrast changes between arms, or use another formulation. A within-group change alone would not answer whether the strategies differ; the comparison of interest ordinarily concerns the between-group effect, defined in advance.

How should the primary endpoint be understood?

The listed primary efficacy variable is total reduction in measured lung water over the first seven days of treatment. General: A change measure depends on the definition of its starting measurement, how later measurements are collected, and how those measurements are summarized. Repeated measurements may require a prespecified method for handling timing and incomplete observations. The registry record does not report the measurement schedule, unit, summary rule, or analysis model. No endpoint estimate or uncertainty measure is reported, so an effect size cannot be interpreted.

What is a confidence interval?

General: A confidence interval expresses the statistical uncertainty around an estimated effect under a particular analysis and its assumptions. Its width reflects both the observed data and the method used to estimate the effect. It is not reported for the primary endpoint in this registry record. Without an estimate and interval, readers cannot judge the range of effects compatible with the trial's analyzed data or the precision of an efficacy comparison.

What do significance tests tell readers?

General: A significance test evaluates how compatible data are with a specified null hypothesis under the assumed model. A p-value does not measure the size or importance of an effect, and it cannot repair limitations in design, measurement, or missing data. The registry record does not report a primary endpoint test or p-value. It also does not report the planned statistical model, significance threshold for the efficacy analysis, or whether any adjustment was planned.

Why does missing information matter?

General: Missing outcome data can affect an estimate when the chance of missingness is related to participants' outcomes or treatment assignment. Appropriate methods depend on the amount and reasons for missingness and on assumptions about the unobserved values. The registry record does not report endpoint completeness, reasons for missingness, imputation methods, or sensitivity analyses. It therefore is not possible to assess how missing measurements would have been handled.

How should the sample-size illustrations be read?

The sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They are not the trial's reported sample-size justification. General: Planning calculations estimate the amount of information a future study might need under stated assumptions. They do not describe the power actually achieved after a study, and they cannot replace an estimate and uncertainty interval from the completed analysis. The registry does not report the protocol's sample-size rationale or an analyzed efficacy effect.

The safety counts are descriptive entries, not a substitute for an efficacy analysis. The registry does not report statistical comparisons for these outcomes, an adverse-event analysis plan, or event attribution. Overall, the design features and planned endpoint are documented, but the methods used to analyze outcomes are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. It does not say whether the investigators intended to adjust for testing multiple outcomes, multiple time points, or multiple treatment comparisons. The primary endpoint is described as total reduction in measured lung water over the first seven days of treatment, but the record also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The precise set of planned tests and the intended primary contrast are not reported.

General: Multiplicity arises when several hypotheses are tested or several opportunities are available to identify a result. Without a prespecified strategy, selective emphasis on favorable findings can make nominal significance levels misleading. Adjustment methods and hierarchical testing are possible approaches, but the record does not identify any approach used or planned. Since no efficacy analyses are reported, there are no reported primary or secondary p-values to interpret.

The registry record does not report missing endpoint counts, participant flow by analysis status, reasons for missingness, or methods for handling missing data. It also does not identify an intention-to-treat population, a per-protocol population, or another analysis population. General: These definitions matter because they determine which randomized participants contribute to a particular estimate and how departures from assigned treatment are handled. Without the population definition and flow details, readers cannot assess the scope of any hypothetical analysis; no such analysis is reported.

The record states that analyses were not conducted after the principal investigator departed and that OHSU will not complete analyses. As a result, multiplicity, missing-data handling, and analysis-population choices are not merely unreported technical details accompanying results: there are no reported efficacy results to interpret under those choices.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (31.2%).

The registry reports serious adverse events, other adverse events, and deaths by arm. In Modified FACTT (Control), serious adverse events were recorded for 2 of 17 participants at risk and other adverse events for 1 of 17. In EVLW, serious adverse events were recorded for 5 of 16 participants at risk and other adverse events for 2 of 16. The deaths field lists 2 for Modified FACTT (Control) and 5 for EVLW. Death is also listed as a top serious term at 31.2%.

These entries should be read as descriptive counts, not as proof that a treatment caused or prevented an event. The registry record does not report a statistical comparison, event attribution, follow-up period for these safety outcomes, or detailed definitions of the event categories. It also does not explain the relation between the deaths field and the serious adverse-event counts. The 31.2% entry is reported among the top serious terms, but the record does not give enough context to treat it as an arm-specific estimate.

General: Safety interpretation depends on the events collected, the period of observation, the number of participants followed, and how events are classified. Small counts can be imprecise, and descriptive differences alone do not establish a causal effect. These registry figures should therefore be understood as recorded safety information, with important comparative and contextual details not reported in the registry record.

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

The record documents a randomized phase 2 comparison of an EVLW-directed treatment strategy and Modified FACTT management for acute lung injury. It states that the primary efficacy variable was total reduction in measured lung water during the first seven days of treatment. However, no efficacy analysis is reported. There is no arm-specific endpoint result, between-arm estimate, confidence interval, or test result from which to assess whether the strategies differed on the planned measure.

The absence of an efficacy analysis is not evidence that the strategies had the same effect, nor does it establish that either strategy was better. It means the registry record cannot answer the primary efficacy question. The recorded explanation is that the principal investigator departed the institution before analyses were conducted, OHSU will not complete analyses, and the study device is no longer manufactured. These are explanations for the missing analysis, not findings about treatment effects.

The safety entries document serious adverse events, other adverse events, and deaths by arm. They do not establish causation or provide a formal safety comparison. The record does not report event timing, attribution, or a statistical analysis of the safety outcomes. The observed counts should not be used to infer what would happen in another population or setting.

General: A randomized design can support causal comparisons when outcomes are measured and analyzed according to a suitable plan. But a design description alone cannot yield an effect estimate. Readers need analyzed outcomes, information about who contributed data, and an account of uncertainty and missingness to judge what the study's results mean. Those elements are not reported for the primary endpoint.

Consequently, the most defensible conclusion is limited to what the registry documents: the planned intervention strategies and primary endpoint, the completed status, a statement that analyses were not conducted, and descriptive safety counts. It does not support a conclusion about the efficacy of EVLW-directed treatment or a comparative conclusion about safety.

13. Why This Trial Matters Statistically

This trial is statistically important as an example of the distinction between a registered design and an analyzed result. A randomized comparison can be carefully framed, with an intervention strategy, comparator, and primary endpoint, yet still leave its central question unanswered if no endpoint analysis is completed or reported. Here, the registry identifies the primary efficacy variable as total reduction in measured lung water during the first seven days of treatment, but provides no analysis of that outcome.

The record also illustrates why endpoint definitions and analysis plans matter. A change in measured lung water can depend on how measurements are timed, combined, and compared. The registry does not report those details or the intended statistical model. Even if an endpoint title is clear at a broad level, readers need operational definitions and analysis details to understand the estimate and its uncertainty.

The safety entries show another statistical distinction: counts can be reported without supporting a comparative inference. Without a reported analysis plan, event timing, or attribution, the arm-specific counts are descriptive. They are not equivalent to an adjusted or uncertainty-qualified estimate of treatment effect.

The record's sample-size assumptions further underscore the difference between planning and results. Planning illustrations rely on assumptions and are not observed power. They cannot establish what the trial learned about efficacy when the primary outcome analysis is absent. The record does not report the protocol's sample-size rationale.

For clinical researchers and biostatisticians, this study highlights the value of transparent outcome definitions, prespecified analysis methods, complete reporting, and clear explanations when analyses are not performed. It also shows why registry status and enrollment alone should not be mistaken for evidence addressing a treatment question. The available material documents a study and its recorded safety counts, while leaving the planned efficacy comparison unresolved.

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 central limitation for interpreting this trial is that the registry record reports no analyses. It states that the principal investigator departed the institution before analyses were conducted and that OHSU will not complete them. Consequently, the primary efficacy endpoint has no reported result, estimate, uncertainty interval, or statistical test. The listed completed status does not imply that the planned efficacy comparison was analyzed.

The primary endpoint description gives a broad measure and timeframe but does not report the measurement unit, exact calculation of total reduction, schedule of measurements, or the analysis model. The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. The intended contrast and handling of those categories or time points are not reported.

The study descriptions are incomplete. The Modified FACTT arm description is truncated, and the record does not provide full eligibility criteria, baseline characteristics, participant flow, or information about adherence. Although single masking is listed, the identity of the masked parties and the masking procedures are not reported. The randomization procedure and allocation concealment are also not reported.

For safety, the registry provides counts but not event timing, attribution, statistical comparisons, or enough context to interpret the top serious term as an arm-specific measure. The analysis populations and missing-data procedures are not reported. The record also notes that the study device is no longer manufactured, which may limit further evaluation using that device, but does not alter the interpretation of the recorded counts.

These limitations prevent an efficacy conclusion and restrict safety interpretation to descriptive reporting. The registry record does not report further analyses that would resolve these uncertainties.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Hemodynamics and Extravascular Lung Water in Acute Lung Injury — NCT00624650.
• Registry record last updated 2019-09-10; status last verified 2019-08.
• Results first posted 2019-09-10.
• 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

The registry record describes NCT00624650, “Hemodynamics and Extravascular Lung Water in Acute Lung Injury,” as a randomized, single-masked, parallel-group phase 2 trial sponsored by Oregon Health and Science University. It lists acute lung injury as the condition, enrollment of 33, start date 2008-02, primary completion 2011-01, and completed status.

The trial compared EVLW-directed treatment with Modified FACTT management. Its primary efficacy variable was total reduction in measured lung water during the first seven days of treatment. The registry states that analyses were not conducted and that OHSU will not complete them. No efficacy result is reported. Safety entries include serious adverse events, other adverse events, and deaths by arm, but no comparative analysis or event attribution is reported.

The registry does not report the statistical analysis plan, analysis populations, missing-data methods, or the protocol's sample-size justification. The available record supports a description of the planned study and recorded safety counts, not an efficacy conclusion.