Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery (NCT02221037), a randomized phase 2 study. The primary outcome is Baseline Adjusted Change in Pulmonary Vascular Permeability Index (PVPI) on Completion of Surgery.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group trial sponsored by GlaxoSmithKline. Its official title describes a multi-centre, single-dose design in patients undergoing oesophagectomy. The registry record lists an enrollment of 35 and a status of terminated. The record gives a study start of 2015-04-28 and a primary completion date of 2017-06-28. It describes a planned study of approximately 40 patients per group, but does not report a sample-size justification or the reason for termination.

Participants were assigned to GSK2862277 or placebo. Both were administered as a single inhaled aerosol dose approximately 1-3 hours before scheduled surgery. The recorded endpoint groups also distinguish the location of post-surgical bronchoalveolar lavage sampling: collapsed lung or ventilated lung. Consequently, the posted primary endpoint summaries consist of four groups: placebo with sampling from either lung location, and GSK2862277 26 mg with sampling from either lung location.

The primary endpoint was baseline-adjusted change in pulmonary vascular permeability index on completion of surgery. Baseline was measured immediately before surgery on Day 1, and the post-baseline measure was taken at completion of surgery on Day 1. The primary endpoint population was PP1, a per-protocol population defined by treatment actually received matching randomized treatment for both study drug and lavage sampling location. The record also lists 21 posted secondary outcomes, including lung water, oxygenation, safety, laboratory, electrocardiogram, and vital-sign measures.

The registry record does not report the randomization procedure, allocation ratio, planned analysis model, or details of any interim analyses. Although the study is described as double-blind, the record does not state who was masked or how masking was maintained. These details should not be inferred from the design label alone.

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.

Before assignment: A total of 54 participants (included 2 participants who were screen-failures and were re-screened) were screened, of which 21 participants (2 re-entered study) were screen-failures (SF). Reasons for SF: study procedure could not be performed (4), inclusion/exclusion criteria not met (14), study closed/terminated (1) and investigator discretion (2).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PP1 Population.

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: Safety Population which comprised of all participants who received at least one complete dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Baseline Adjusted Change in Pulmonary Vascular Permeability Index (PVPI) on Completion of Surgery, measured over Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery).

Pulmonary vascular permeability index (PVPI) is a derived measure based on extra vascular lung water. The registry description characterizes it as less variable than extra vascular lung water index (EVLWI). PVPI was measured using single-indicator transpulmonary thermodilution with an indwelling PiCCO catheter. The endpoint is expressed as a ratio.

The recorded change is the value measured at completion of surgery minus the baseline value immediately before surgery on Day 1. A change near zero would indicate little difference between these measured time points; a positive or negative value indicates the direction of the observed within-participant change. These descriptions explain the scale and direction of the endpoint, not whether a change is clinically important.

The endpoint was selected to capture a biological or physiological marker around the operative period, when the registry summary describes lung injury as a concern. It is not itself a direct count of clinical ARDS events or a patient-reported outcome. The registry record notes the relationship of PVPI to EVLW but does not report a threshold for clinically meaningful change or explain how a particular change should be interpreted clinically.

Group means and standard deviations are posted for the four combinations of treatment and lavage location. A treatment-effect estimate with uncertainty is not reported in the registry record, so the group summaries alone do not establish the size or precision of a comparative effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A continuous outcome is measured on a numerical scale. For PVPI, the registry record reports the mean change and standard deviation within each treatment and lavage-location group. The mean describes the group's average change from baseline to completion of surgery. The standard deviation describes how spread out the individual changes were around that average. These are descriptive statistics; neither one is, by itself, a treatment-effect test.

What would a treatment contrast represent?

A treatment contrast would compare outcomes between participants assigned to GSK2862277 and participants assigned to placebo under a specified analysis. Depending on the model, that estimate might account for baseline values, lavage sampling location, or other factors. The registry record does not report the statistical model or a comparative estimate. It therefore does not establish whether any particular adjustment was planned or performed.

A confidence interval, in general, describes uncertainty around an estimated quantity under the assumptions of the analysis. For a treatment contrast, it would help readers judge both the range of effects compatible with the data and the precision of the estimate. No confidence interval for a treatment contrast is reported in the registry record. A p-value, in general, summarizes how incompatible observed data are with a specified null hypothesis under an analysis model; it is not a measure of clinical importance. No primary-outcome p-value is reported in the registry record.

Why consider variability?

Observed changes can vary between participants. Standard deviations of 0.367, 0.664, 0.536, and 0.449 are reported for the four respective endpoint groups. If outcomes vary substantially relative to the effect a study aims to detect, estimates can be less precise. This is a general statistical point, not evidence that any particular effect exists in this trial. The posted summaries do not provide an estimate of a treatment contrast or its uncertainty.

Over-dispersion is a general concern when a statistical model assumes less variability than the data actually exhibit. It can make standard errors and inferential conclusions unreliable if not addressed. The registry record does not report a model for the primary outcome or an assessment of over-dispersion. It would therefore be inappropriate to claim that over-dispersion occurred or that a particular correction was used.

What do the four groups imply?

The summaries are divided by treatment and by whether lavage sampling was from the collapsed or ventilated lung. This distinction is part of the recorded study structure and should be retained when interpreting the means. The two sampling locations should not be collapsed into one treatment comparison without an analysis plan and appropriate participant-level data. The registry record does not report a comparison within each location or a test of whether the treatment contrast differed by location.

The mean values are 0.0, 0.11, -0.18, and 0.21 for the placebo collapsed-lung, placebo ventilated-lung, GSK2862277 collapsed-lung, and GSK2862277 ventilated-lung groups, respectively. These values describe group averages, not individual responses. Differences between any pair of means are not reported as treatment-effect estimates in the registry record and are not recalculated.

Planning estimates and observed evidence

Sample-size calculations are planning illustrations about how much information a future or hypothetical study might need under stated assumptions. They are not observed power, and they do not establish what effect the trial found. The registry record does not report its own sample-size justification. The displayed planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. Any resulting planning values should be interpreted as illustrations rather than characteristics of the enrolled trial.

In general, planning estimates depend on assumptions about the target effect, variability, analysis, and allocation. If the assumed effect is smaller, a study generally needs more information to detect it under otherwise comparable assumptions. This is a general principle, not a newly calculated result for this trial. The planning exercise does not repair the absence of a reported primary-outcome analysis.

Why group size and population definitions matter

The primary endpoint is described for the PP1 population. The registry defines PP1 as participants in the Safety population whose treatment actually received matched randomized treatment for both study drug and lavage sampling location. This definition means the endpoint summaries are tied to a particular analysis population. The record does not report a separate intention-to-treat primary analysis or provide a participant flow explaining inclusion and exclusion from PP1.

The endpoint group counts are 5, 10, 5, and 8. Safety denominators differ in some groups, and the record does not explain the difference between those denominators and the endpoint counts. A reader should not assume that every randomized participant contributed an endpoint measurement or infer the reason for any difference. The handling of missing values, the assumptions used for missing data, and any sensitivity analyses are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo (BAL Collapsed Lung)", "Placebo (BAL Ventilated Lung)", "GSK2862277 26 mg (BAL Collapsed Lung)", "GSK2862277 26 mg (BAL Ventilated Lung)")
n   <- c(5, 10, 5, 8)
m   <- c(0, 0.11, -0.18, 0.21)
sp  <- c(0.367, 0.664, 0.536, 0.449)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo (BAL Collapsed Lung)  5  0.000  0.367  -0.456  0.456
CARM  Placebo (BAL Ventilated Lung)  10  0.110  0.664  -0.365  0.585
CARM  GSK2862277 26 mg (BAL Collapsed Lung)  5  -0.180  0.536  -0.846  0.486
CARM  GSK2862277 26 mg (BAL Ventilated Lung)  8  0.210  0.449  -0.165  0.585

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 21 posted secondary outcomes in addition to the primary endpoint. These include lung water and oxygenation measures, adverse events, serious adverse events, and categories of laboratory, electrocardiogram, and vital-sign findings. When a study examines many outcomes, the chance of at least one apparently notable result can rise if each is assessed separately. This is a general statistical concern, not evidence that a false-positive result occurred in this trial.

A multiplicity strategy might identify a primary outcome, order or group secondary outcomes, or adjust inferential thresholds. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan. It also reports no primary-outcome analyses. It is therefore not possible to determine from the record how multiple outcomes were handled inferentially.

Missing-data methods matter because outcome measurements may be unavailable for some participants. The registry record provides endpoint group counts and describes the PP1 population, but does not report the number or reasons for missing primary endpoint values, the method used to handle missing measurements, or sensitivity analyses. These details are not reported in the registry record. No assumptions about why a value might be missing should be made from the group summaries alone.

The defined primary population is PP1: participants in the Safety population whose treatment received matched randomization for both study drug and lavage sampling location. The record does not report whether an intention-to-treat population was used for the primary analysis, nor does it explain participant disposition between randomization, safety, and PP1 populations. The difference between the posted endpoint counts and some safety denominators is not explained in the registry record.

These omissions limit assessment of the robustness of any comparative conclusion. They do not establish that an analysis or a missing-data procedure was not performed elsewhere; they mean those details are not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (40.0%), pneumonia (25.0%), anastomotic leak (22.2%), atrial fibrillation (20.0%), diaphragmatic hernia (20.0%).

The safety results use group-specific denominators that are not identical to all of the primary endpoint group counts. For serious adverse events, the registry record lists 3 of 5 participants in the placebo, collapsed-lung group; 5 of 11 in the placebo, ventilated-lung group; 5 of 8 in the GSK2862277 26 mg, collapsed-lung group; and 4 of 9 in the GSK2862277 26 mg, ventilated-lung group. It reports no deaths in these groups. These are descriptive participant counts, not estimates of comparative risk.

For other adverse events, the record lists 5 of 5, 10 of 11, 5 of 8, and 8 of 9 participants, respectively, in those same groups. Serious adverse events and other adverse events are separate categories in the record. The record also lists serious adverse event terms, including pulmonary embolism, pneumonia, anastomotic leak, atrial fibrillation, diaphragmatic hernia, and small intestinal obstruction, with percentages attached to each term. Those percentages should be read in the context of the registry's event reporting and denominators; they do not by themselves establish causation or comparative safety.

The safety counts are not proof that a treatment caused an event or prevented one. The record does not report a statistical comparison of safety outcomes, an attribution analysis, or the exposure time needed for a rate comparison. The reason the safety denominators differ from some primary endpoint counts is not reported in the registry record.

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

The posted primary endpoint data describe average changes in PVPI from immediately before surgery to completion of surgery in four groups defined by treatment and lavage location. The means and standard deviations provide a view of observed group-level changes and within-group variability. They do not provide a comparative treatment estimate, and no statistical analysis results for the primary endpoint are reported in the registry record.

Accordingly, the group summaries do not establish whether GSK2862277 differed from placebo, whether any difference was clinically meaningful, or how precisely a treatment difference could be estimated. A mean is not a statement about every participant, and a standard deviation is not a measure of certainty around a treatment effect. The registry record does not report a threshold that would identify a clinically important PVPI change.

The study description frames the work as an investigation of biological and physiological markers around oesophagectomy, with particular interest in lung injury during and immediately after surgery. The primary endpoint is a physiological measure, not a direct assessment of clinical ARDS incidence. The record's rationale notes that clinical ARDS can develop in the immediate post-operative period, but that context does not make the PVPI outcome equivalent to an ARDS outcome.

The record's terminated status and enrollment of 35 are important context, as is the plan for approximately 40 patients per group. The reason for termination and the study's sample-size justification are not reported in the registry record. These registry entries should not be used to infer the reason for the lack of a comparative analysis or to make claims about the treatment's effects.

Overall, the registry record supports descriptive statements about the posted group means, variation, and safety counts. It does not support a conclusion that the study demonstrated benefit, lack of benefit, or equivalence between groups.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized design and a published treatment comparison are distinct parts of interpreting clinical research. Randomization is intended to support a fair comparison, but the primary endpoint results posted in the registry record are group-level means and standard deviations. Without a reported contrast and uncertainty, readers cannot assess the estimated treatment effect from the record.

It also illustrates the importance of preserving design structure in analysis. The registry separates results by treatment and by lavage sampling location. Treating all GSK2862277 participants as one group and all placebo participants as another would disregard that structure unless a suitable analysis justified the combination. The record does not report such an analysis.

The difference between descriptive summaries and inferential results is central. Means describe observed averages, and standard deviations describe variation. A confidence interval or a model-based contrast would address uncertainty in a comparison. Neither a contrast nor its confidence interval is reported for the primary endpoint in the registry record.

Finally, the record makes clear that endpoint populations, safety denominators, and missing-data handling need explanation. The PP1 definition is specific, but participant flow and missing-data methods are not reported. This limits readers' ability to understand precisely who contributed to each result. These are general lessons in interpreting registry results, not evidence of a particular error in this trial.

15. 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 main limitation of the posted primary endpoint results is the absence of a treatment comparison and its uncertainty. The registry record reports four group means and standard deviations, but no primary-outcome analysis results, confidence interval, or p-value. The means should therefore be read descriptively rather than as evidence of a difference between treatments.

The endpoint summaries come from the PP1 population, defined by matching treatment received to randomized treatment for both study drug and lavage sampling location. The registry record does not report an intention-to-treat primary analysis or a participant-flow account that would clarify how participants moved into the PP1 and Safety populations. The endpoint counts also differ from some safety denominators, and the reason is not reported.

Although enrollment was 35 and the study description planned approximately 40 patients per group, a sample-size justification is not reported in the registry record. The record also says the trial was terminated but does not report why. These details constrain interpretation of the amount of evidence available; they do not explain the missing comparative results.

The posted endpoint is a physiological marker measured at completion of surgery, rather than a direct clinical outcome such as ARDS incidence. The registry record does not state a threshold for clinically important change in PVPI. It also does not report the analysis model, multiplicity strategy, missing-data procedures, or sensitivity analyses. The absence of these details from the registry record limits assessment of analytical choices and robustness.

Safety findings are reported as participant counts by group, without a statistical comparison or information sufficient to infer causation. Differences in the reported denominators should not be interpreted without participant disposition and event-reporting details, which are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery — NCT02221037.
• Registry record last updated 2020-10-27; status last verified 2020-10.
• Results first posted 2019-01-11.
• 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.

19. Record Summary

NCT02221037 is a Phase 2 randomized, double-blind, placebo-controlled parallel-group trial of single-dose inhaled GSK2862277 in patients undergoing oesophagectomy. The registry record lists enrollment of 35, terminated status, a study start of 2015-04-28, and primary completion on 2017-06-28.

The primary endpoint was baseline-adjusted change in PVPI on completion of surgery, measured in the PP1 population. Posted group summaries are separated by treatment and whether lavage sampling was from the collapsed or ventilated lung. The registry record does not report a statistical analysis comparing treatments for this endpoint.

The record lists 21 posted secondary outcomes and descriptive safety counts. It does not report the reason for termination, a sample-size justification, the primary analysis model, missing-data procedures, or a multiplicity strategy.