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 The Effects of Preceding LPS Administration on the Fluenz-induced Immune Response (NCT02642237), a randomized na study. The primary outcome is Peak Levels of Interferon Gamma-induced Protein 10 (IP-10) in Nasal Wash Fluid.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02642237 |
| Phase | NA |
| Condition | Innate Immune Response, Immune Tolerance |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Radboud University Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy volunteers. The registry reports an enrollment of 30 and describes the two groups as healthy volunteers. It does not provide further demographic characteristics, eligibility details, or a description of the analysis population for the primary outcome. The results therefore apply to the volunteers enrolled in this study as described in the record; they should not be assumed to represent other populations.
Intervention
One group received intravenous LPS, an endotoxin challenge, followed by intranasal Fluenz, a live-attenuated influenza vaccine. The study title and summary frame this sequence as a way to examine bacterial-viral interactions. The registry does not provide further procedural details about administration or the interval between the challenges in the arm description.
Comparator
The comparison group received intravenous placebo followed by intranasal Fluenz. Thus, both groups received Fluenz, while the preceding intravenous administration differed: LPS in one group and placebo in the other. The registry describes randomized allocation, but does not report the allocation method or details of concealment.
Primary question
The primary question was whether the group receiving preceding LPS had a different peak level of interferon gamma-induced protein 10, or IP-10, in nasal-wash fluid from the group receiving preceding placebo. The measurement was reported 35 days after Fluenz inoculation. IP-10 is described in the registry as a marker of viral-induced inflammation, with higher levels indicating a more pronounced inflammatory response upon viral infection. The record gives a geometric mean and 95% confidence interval for each group, but does not report an inferential comparison between groups. The question can therefore be described, but the posted results do not establish a statistical estimate or test of the between-group difference.
3. Trial Design
The registry describes NCT02642237 as a randomized, parallel-group study in healthy volunteers. Its title identifies the question as the effect of preceding LPS administration on the immune response elicited by a subsequent Fluenz challenge. The record lists the study as completed and gives Radboud University Medical Center as the sponsor. Phase is recorded as NA.
The two arm descriptions differ in the intravenous administration that precedes intranasal Fluenz. The LPS-Fluenz group received endotoxin followed by Fluenz; the Placebo-Fluenz group received placebo followed by Fluenz. Each arm has a reported outcome group size of 15. The registry enrollment is 30. These are reported design and outcome details, not an independent reconstruction of participant flow.
Masking is listed as none. This means the record does not describe the study as masked; it does not establish which people, if any, were aware of allocation at each stage. The allocation method, concealment procedures, and protocol details beyond the listed design are not reported in the registry record. The parallel model means the record describes separate groups receiving the two sequences, rather than a crossover comparison.
The primary outcome is peak IP-10 in nasal-wash fluid, with results reported 35 days after Fluenz inoculation. Although one outcome measure is listed, the registry reports no analyses. It provides arm-level estimates but does not post a formal treatment-effect estimate, hypothesis test, or analysis population for this outcome. These omissions limit how much can be concluded about the planned or conducted statistical comparison.
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 | LPS-Fluenz | Placebo-Fluenz |
|---|---|---|
| STARTED | 15 | 15 |
| COMPLETED | 15 | 15 |
| NOT COMPLETED | 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 | LPS-Fluenz | Placebo-Fluenz | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 15 | 30 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 | 15 | 30 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 15 | 15 | 30 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 15 | 15 | 30 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Netherlands | participants | 15 | 15 | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Peak Levels of Interferon Gamma-induced Protein 10 (IP-10) in Nasal Wash Fluid, measured over 35 days after FLuenz inoculation.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | pg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the peak level of interferon gamma-induced protein 10 (IP-10) in nasal-wash fluid, expressed in pg/mL, with the timeframe recorded as 35 days after Fluenz inoculation. The registry describes IP-10 as a marker of viral-induced inflammation and states that higher levels indicate a more pronounced inflammatory response upon a viral infection. The endpoint is therefore intended to capture an inflammatory response following the Fluenz challenge.
The reported summary measure is the geometric mean, accompanied by a 95% confidence interval for each group. A geometric mean is a summary suited to positive measurements that may vary multiplicatively; it summarizes values on a logarithmic scale and expresses the result back on the original scale. This is a general statistical explanation, not a claim about the distribution of individual IP-10 measurements in this study. The record does not report individual measurements, the endpoint’s operational definition of “peak,” or further details on how nasal-wash samples were processed.
The endpoint is a laboratory marker, not a clinical outcome. Its interpretation concerns the measured inflammatory response, as described in the registry. The record does not establish how this marker relates to symptoms, disease course, or clinical benefit.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a geometric mean peak IP-10 level of 2000 pg/mL in the LPS-Fluenz group, with a 95% confidence interval from 900 to 3000 pg/mL. For the Placebo-Fluenz group, the reported geometric mean is 1900 pg/mL, with a 95% confidence interval from 900 to 2800 pg/mL. Both summaries refer to nasal-wash fluid at the timeframe recorded as 35 days after Fluenz inoculation.
These values describe each group separately. The record does not report a between-group estimate, confidence interval for the contrast, p-value, or other inferential analysis. It is therefore not possible to use the registry’s posted results to quantify the estimated difference between the preceding-LPS and preceding-placebo sequences or to judge its statistical precision as a contrast. The fact that the arm-level confidence intervals overlap does not itself provide a formal test of the difference. As a general statistical point, uncertainty for a contrast depends on the contrast estimate and its variability, not just on visually comparing two separate intervals.
The intervals indicate uncertainty around the reported group-level geometric means. A confidence interval is a method for expressing the precision of an estimate under a statistical model; it does not mean that there is a 95% probability that the fixed underlying group mean lies within the particular interval. The record does not describe the interval calculation in further detail. The width of the reported intervals also cautions against treating the point estimates as exact descriptions of the groups’ underlying responses.
There are 15 participants reported in each outcome arm. Those group sizes provide context for the arm-level summaries, but they do not replace a formal comparison. The registry’s analysis count is zero, and it flags values as missing or not estimable for a two-arm comparison for this other endpoint. Consequently, the posted arm summaries should not be presented as evidence that the preceding LPS sequence increased, reduced, or left unchanged the endpoint relative to placebo.
The primary endpoint is a marker of viral-induced inflammation according to the registry description. The reported values concern this marker at the specified timeframe, not a direct measure of infection, symptoms, or health outcome. No secondary outcomes are posted. The most defensible reading is therefore limited: the record gives two group-level estimates with substantial interval uncertainty and does not provide the comparative analysis needed to resolve the study’s primary question statistically.
9. Statistical Methods Explained
The registry labels allocation as randomized, the model as parallel, and masking as none. Random allocation is a design approach intended, in general, to reduce systematic differences between groups at the point of assignment. The record does not describe how the random sequence was generated, how allocation was concealed, or whether any safeguards were used. It is not possible to infer those procedures from the word “randomized” alone. A parallel design means participants are assigned to one sequence of study administrations rather than receiving both sequences in turn. The absence of masking may be relevant to expectations or study conduct, but the registry does not describe who knew the assignments or whether knowledge could have influenced measurement.
What do the reported summaries represent?
The primary measure is the geometric mean of peak IP-10 in nasal-wash fluid. Unlike an arithmetic mean, a geometric mean is based on multiplying values, equivalently averaging their logarithms and transforming the result back to the measurement scale. In general, this can be useful when measurements are positive and their variability is naturally expressed in relative or multiplicative terms. The registry does not report the distribution of the individual observations or the rationale for selecting this summary, so the appropriateness of the measure cannot be assessed from the record alone.
Each geometric mean is accompanied by a 95% confidence interval. In general, an interval communicates the statistical uncertainty of an estimate under the method’s assumptions. A narrower interval indicates greater precision for that estimate, while a wider interval indicates more uncertainty. The interval is not a range containing every participant’s result, and it does not describe the full distribution of individual observations. The registry does not state how the intervals were constructed or whether they were based on a particular transformation or model.
What would a group comparison require?
The scientific question concerns the difference between the two sequences, not whether either group’s mean differs from a benchmark. A formal comparison would report a contrast between the groups and quantify its uncertainty, usually with an interval and possibly a hypothesis test. Depending on the analysis method, the contrast could be expressed on the original scale or on a transformed scale. The registry does not post such a contrast, its confidence interval, a p-value, or the method used for a comparison. It lists no analyses and marks the two-arm comparison as missing or not estimable for this endpoint. The separate group estimates cannot be substituted for a comparative result.
As a general point, statistical significance and clinical importance are different questions. A test addresses compatibility with a specified statistical null under its assumptions; it does not by itself establish whether an effect matters clinically. Conversely, an imprecise estimate can leave a range of effects plausible. In this record there is no posted comparative test or contrast, so neither statistical significance nor the size and precision of a group difference can be evaluated from the arm summaries.
Why do assumptions matter?
Statistical methods rely on assumptions about the data and the process that generated them. For continuous biomarker outcomes, analysts may consider skewness, the measurement scale, outliers, and whether variability changes with the mean. A geometric summary can address some multiplicative patterns, but it does not automatically resolve every distributional issue. The individual data, diagnostics, and analysis model are not reported in the registry record. Over-dispersion is a general concern when observed variability exceeds what a model expects: standard errors can then be too small, making intervals too narrow and tests too optimistic if the model does not account for that extra variation. The record does not indicate whether over-dispersion was assessed or whether it is relevant to these measurements.
The sample-size assumptions described for planning illustrations are two-sided significance level 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s original design rationale or a report of observed power. The registry does not provide the numeric outputs of those illustrations in the registry record for this analysis, so no sample-size target can be stated. A planning calculation based on an observed effect is also not a substitute for a prespecified design justification.
No recalculated comparative result is available. In general, a recalculation from summary statistics would be an unadjusted estimate and would not replace a sponsor’s prespecified analysis. Here, the registry reports no sponsor analysis or other formal analysis to take precedence. The arm-level numbers should therefore remain descriptive rather than being converted into a newly calculated treatment-effect estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and reports no secondary outcomes. It does not report a multiplicity adjustment, a hierarchy of outcomes, or a plan for handling multiple comparisons. With no posted secondary results or analysis set, the extent to which multiple statistical questions were considered during the study cannot be established. The absence of a posted adjustment is not evidence that no additional analyses were performed; the analysis count is listed as zero, and further analysis details are not reported in the registry record.
Missing-data methods are not reported in the registry record. The posted outcome summaries do not explain whether all participants with outcome measurements were included, how unavailable samples were handled, or whether any imputation or sensitivity analysis was used. The outcome group sizes are listed as 15 for each arm, but these figures alone do not establish completeness of the endpoint data or the handling of any missing measurements.
The analysis population is also not reported. The registry does not say whether the primary outcome was analyzed according to randomized assignment, among participants who received the assigned sequence, or in another defined subset. It gives no participant flow or analysis-population criteria for this endpoint. Such information matters because excluding participants after allocation can affect the comparability intended by randomization. Without a stated population and missing-data approach, the extent to which the reported arm summaries reflect all randomized volunteers cannot be determined.
There is no reported protocol-based statistical analysis plan in the record. Accordingly, it is not possible to establish whether the endpoint, analysis population, handling of missing data, or multiplicity approach was specified before the data were examined.
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 |
|---|---|---|---|
| LPS-Fluenz | 0 | 15 | 0.0% |
| Placebo-Fluenz | 0 | 15 | 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 |
|---|---|
| LPS-Fluenz | 0 of 15 |
| Placebo-Fluenz | 0 of 15 |
For the LPS-Fluenz group, the registry lists 0 participants affected by serious adverse events among 15 at risk and 0 participants affected by other adverse events among 15 at risk. For the Placebo-Fluenz group, it likewise lists 0 affected by serious adverse events among 15 at risk and 0 affected by other adverse events among 15 at risk. Death counts are not reported in the registry record. No serious adverse event terms are listed.
These figures describe the posted adverse-event counts for the categories and groups recorded. They do not show that no adverse events of any kind occurred outside the categories or reporting period captured in the registry. The record does not provide definitions, ascertainment procedures, follow-up duration for safety, or further detail about event severity and types. A zero count in a group of this size also does not establish that an event cannot occur or precisely quantify the risk beyond the observed record. These are descriptive registry figures, not a complete safety assessment or a basis for medical advice.
12. What the Result Does, and Does Not, Mean
The result documents group-level peak IP-10 estimates following the two administration sequences. The geometric mean was 2000 pg/mL in the LPS-Fluenz group and 1900 pg/mL in the Placebo-Fluenz group, with the reported 95% confidence intervals extending from 900 to 3000 pg/mL and from 900 to 2800 pg/mL, respectively. The endpoint was measured in nasal-wash fluid 35 days after Fluenz inoculation. The registry characterizes IP-10 as a marker of viral-induced inflammation.
What the result does not provide is a statistical estimate of the difference between groups. There is no posted contrast, contrast interval, or p-value, and the registry lists no analyses. The two arm-specific means cannot establish whether preceding LPS was associated with a difference in peak IP-10 compared with preceding placebo. Nor does the lack of a posted contrast establish that the sequences produced the same response.
The endpoint is a biomarker rather than a patient-centered clinical outcome. The record does not report whether differences in this measurement correspond to symptoms, infection severity, or other health outcomes. The study summary describes the bacterial-viral interaction as a model relevant to sepsis and influenza, but this experimental challenge in healthy volunteers does not itself report clinical outcomes for people with either condition. The registry does not establish that the findings can be generalized to other populations or settings.
The confidence intervals convey uncertainty around the group estimates, not the range of individual responses. Without a comparative analysis, interpretation should remain descriptive. The registry provides a focused laboratory outcome and a randomized design description, but incomplete statistical reporting prevents a conclusion about the magnitude, precision, or statistical evidence for a between-group effect.
13. Why This Trial Matters Statistically
This trial raises a statistically clear question: whether preceding an intranasal Fluenz challenge with intravenous LPS is associated with a different peak nasal IP-10 response than preceding Fluenz with intravenous placebo. The randomized, parallel-group structure is relevant because the groups receive distinct sequences, while the shared Fluenz challenge makes the preceding administration the principal design contrast described in the record.
The record also illustrates why arm-level estimates are not enough to answer a comparative question. A geometric mean for each group can describe the measured responses, but the scientific comparison requires a direct estimate of the contrast and its uncertainty. Separate confidence intervals offer information about each group’s mean; they do not substitute for a confidence interval around the difference. The registry’s failure to post a formal comparison leaves the central inferential question unresolved in the available record.
Precision is another important consideration. The reported confidence intervals show that the group-level means are not known without uncertainty. In general, readers should distinguish the point estimate from its interval and should avoid treating a point estimate as exact. Here, because no contrast interval is reported, the precision of the between-group effect cannot be judged directly.
The trial is described as exploratory in its official title, and the registry presents a biomarker endpoint in healthy volunteers. Such a setting can address a mechanistic question, but interpretation must stay aligned with the measured outcome and population. The record does not report a clinical endpoint or formal statistical analysis. Its statistical importance lies both in the experimental question and in the limits imposed by reporting: transparent estimation of the contrast, analysis population, and missing-data approach would be needed to make the primary comparison interpretable.
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 primary limitation for statistical interpretation is the absence of a posted two-arm analysis. Although group-level geometric means and confidence intervals are reported, the registry lists no analyses and no formal comparison. A direct effect estimate, its uncertainty, and a test result are therefore unavailable. The arm-specific summaries cannot determine the direction or size of the comparative effect with statistical precision.
The record does not report the analysis population, participant flow, missing-data handling, endpoint data completeness, or sensitivity analyses. It is therefore unclear from the registry whether the reported summaries include all randomized participants or how any unavailable measurements were handled. Details of the randomization method, allocation concealment, and laboratory measurement procedures are also not reported.
Masking is listed as none. The record does not indicate who knew assignments or whether outcome assessment was conducted without knowledge of group. The outcome is a laboratory marker, and no clinical outcomes or secondary outcomes are posted. Its clinical interpretation and relation to outcomes beyond IP-10 are not established by the record.
The study is described as exploratory and concerns healthy volunteers, which limits the scope of conclusions that can be drawn about other populations. The protocol’s statistical plan, multiplicity handling, sample-size justification, interim analyses, and definitions or timing of adverse-event collection are not reported in the registry record. These gaps do not invalidate the posted descriptive values, but they constrain assessment of design choices, analysis robustness, generalizability, and safety reporting.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effects of Preceding LPS Administration on the Fluenz-induced Immune Response — NCT02642237.
- Registry record last updated 2019-05-14; status last verified 2019-05.
- Results first posted 2019-04-19.
- 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
NCT02642237 is a completed randomized, unmasked, parallel-group study sponsored by Radboud University Medical Center. It enrolled healthy volunteers and compared intravenous LPS followed by intranasal Fluenz with intravenous placebo followed by intranasal Fluenz. Phase is recorded as NA.
The primary outcome was peak IP-10 in nasal-wash fluid, reported in pg/mL as a geometric mean with a 95% confidence interval at 35 days after Fluenz inoculation. The LPS-Fluenz group estimate was 2000 pg/mL, with a 95% confidence interval from 900 to 3000 pg/mL; the Placebo-Fluenz estimate was 1900 pg/mL, with a 95% confidence interval from 900 to 2800 pg/mL. The registry lists no analyses and no secondary outcomes. It does not report a formal between-group estimate or analysis details for missing data and analysis populations.