Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection (NCT02095951), a randomized phase 4 study. The primary outcome is Length of Stay (LOS) in Those With 14 Confirmed Catheter Related Infection Cases.

2. Clinical Question

The trial asks whether the timing of ethanol lock therapy (ELT), given alongside systemic antibiotics, is associated with hospital length of stay in children with central catheters and suspected or proven catheter-related infection (CRI). The pre-emptive strategy places ELT within 24 - 36 hours of symptoms or admission; the standard-care strategy places it when the first positive blood culture report is available. The registry describes this as a randomized, unblinded comparison.

The registry identifies length of stay (LOS) and attributable length of stay (ALOS) as outcomes of interest in its study description. It defines ALOS as the hospital days from first CRI symptoms, or admission for those admitted with symptoms, to the first negative blood culture. The posted primary outcome, however, is LOS in confirmed CRI cases; an ALOS result is not reported in the registry record.

3. Trial Design

This is a Phase 4, randomized, unblinded, parallel-group trial. The registry reports enrollment of 30 and a completed status. The listed study dates are 2014-06 for study start and 2016-06 for primary completion. Recruitment was at Children's Hospital of Michigan, a tertiary care pediatric hospital in Detroit, Michigan; the registry does not report other study sites.

Both groups received ELT with systemic antibiotics. The randomized contrast was the timing of ELT: the pre-emptive group received it within 24 - 36 hours of symptoms or admission, while the standard-care group received it at the time of the first positive blood culture report. The registry describes the trial as prospective. Masking is listed as none, so participants and study personnel were not masked according to the record.

The primary outcome is identified as LOS among 14 confirmed catheter-related infection cases. The posted outcome summaries give a mean and standard deviation for each arm: 124.0 hours with a standard deviation of 51.0 in the pre-emptive group, and 208.0 hours with a standard deviation of 151.0 in the standard-care group. The reported outcome counts are 4 and 8, respectively. The registry notes that 1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group. It does not explain how the outcome counts relate to the enrollment figure or provide further detail on the episode-level analysis.

The registry lists catheter sterilization, catheter salvage, adverse events per episode of catheter infection and re-infection as secondary outcomes. Four secondary outcomes are posted, but no analysis results are reported in the registry record. Details of the randomization sequence, allocation concealment, and procedures for handling treatment changes are not reported in the registry record.

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: 3 enrolled participants were removed from the study/analysis for failure to meet final enrollment criteria. Patient participants could be re-enrolled in the study more than once if their infection episodes (cases) were separated by at least 28 days.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

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 Length of Stay (LOS) in Those With 14 Confirmed Catheter Related Infection Cases, measured over Participants will be followed for the duration of hospital stay, an expected average of 2 weeks.

The primary endpoint is hospital length of stay per catheter infection episode or admission, reported as a mean in hours with a standard deviation. LOS measures the duration of hospitalization, an outcome that can reflect the overall course of care. The study description also identifies ALOS, which is intended to focus on days attributed to CRI by measuring from first symptoms, or admission for those admitted with symptoms, to the first negative blood culture. That definition is distinct from total LOS.

The posted primary outcome is titled as LOS in participants with 14 confirmed catheter-related infection cases. The registry does not provide a separate posted ALOS result. The recorded timeframe says participants were followed for the duration of hospital stay, described as an expected average of 2 weeks. That expectation is a timeframe description, not the observed LOS result.

LOS is a continuous measure: each episode or admission can have a duration, and the arm summaries describe the average duration and the spread of recorded durations. The mean is useful for comparing average stays, while the standard deviation describes how dispersed observations are around that average. Neither summary by itself describes the full distribution or establishes why stays differed. Length of stay can also reflect aspects of care beyond the infection itself, so interpreting it as infection-attributable time requires the separate ALOS definition and its corresponding data.

For the posted primary outcome, the pre-emptive arm has a mean of 124.0 hours and standard deviation of 51.0; the standard-care arm has a mean of 208.0 hours and standard deviation of 151.0. These are descriptive summaries. The registry record does not report an inferential comparison or a confidence interval for the arm contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a continuous measure summarized by an arithmetic mean and standard deviation. No inferential analyses are reported in the registry record. The following concepts explain how such summaries and comparisons are generally interpreted; they do not imply that a particular method was used for this trial.

What does the mean describe?

For a continuous outcome such as LOS, the mean is the arithmetic average of the recorded observations in a group. It provides a compact description of the group’s central value, but it does not show every observation or reveal whether most values cluster near the mean. A few unusually long stays can pull a mean upward, especially when the group is small. The reported means are 124.0 hours in the pre-emptive group and 208.0 hours in the standard-care group. The registry record does not provide individual LOS values, medians, ranges or other distributional summaries that would help assess whether the means represent typical stays.

What does the standard deviation describe?

The standard deviation describes how spread out observations are around the group mean. A larger standard deviation indicates more observed variability, not greater uncertainty about the treatment effect by itself. The reported standard deviations are 51.0 hours and 151.0 hours. Interpretation should consider them alongside the outcome counts, which are 4 and 8. With few observations, estimates of both the mean and the spread can be sensitive to individual cases. The standard deviation is not a confidence interval and does not give the likely range for a new participant’s stay.

What would an inferential comparison add?

An inferential analysis would estimate the contrast between groups and quantify uncertainty in that estimate. A confidence interval generally gives a range of values compatible with the data and the assumptions of the analysis; it is not a guarantee that the true effect lies in the interval. A hypothesis test may also report a p-value, which, under the test’s assumptions, describes how unusual data at least as incompatible with a specified null hypothesis would be. A p-value is not the probability that the null hypothesis is true and does not measure clinical importance.

No confidence interval, p-value, or sponsor analysis for the primary outcome is reported in the registry record. The result should therefore be read descriptively rather than as a statistically established difference. No recalculated estimate is presented, and the record does not give the information needed to reproduce an inferential comparison responsibly.

Why does the outcome count matter?

The record labels the outcome as LOS in 14 confirmed catheter-related infection cases, but the arm summaries have counts of 4 and 8. It also notes repeat enrollment of a participant with distinct infection episodes. A statistical analysis needs a clear definition of the unit of analysis: it might be a participant, an admission or an infection episode. When one participant contributes more than one observation, those observations may be correlated rather than independent. General methods for clustered or repeated observations can account for such dependence, but the registry does not say whether such a method was used or how the repeated episodes were handled. The differing outcome descriptions also make the analysis population unclear.

What do the design and sample-size assumptions mean?

Randomization is intended to make treatment groups comparable on average, including for factors that are not measured, but it does not guarantee balance in a small realized sample. The registry lists a randomized, parallel, unblinded design. It does not report the randomization procedure or a detailed statistical plan. A parallel design assigns participants to one of the compared strategies rather than having each participant receive both strategies in sequence.

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These assumptions are not a report of the trial’s original sample-size justification or proof of its design properties. Any such illustration is a planning calculation, not observed power. The registry record does not report a sample-size justification or the numerical planning results.

Why can over-dispersion matter?

In general, over-dispersion means the observed variability is greater than a model assumes. A model that underestimates variability can produce confidence intervals that are too narrow and tests that are too optimistic. For continuous LOS data, skewness, extreme stays, or dependence among repeated episodes can complicate simple model assumptions. The standard deviation in the standard-care group is larger than in the pre-emptive group, but that fact alone does not establish which statistical model is appropriate. The registry record does not report model diagnostics or any adjustment for unequal variability.

Because no inferential analysis is posted, the arm means and standard deviations remain descriptive summaries. The methods used to analyze the primary endpoint, assess assumptions, address repeated episodes, and account for potential confounding after randomization 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("Pre-emptive Ethanol Lock Therapy Group", "Standard of Care Ethanol Lock Therapy Group")
n   <- c(4, 8)
m   <- c(124, 208)
sp  <- c(51, 151)
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  Pre-emptive Ethanol Lock Therapy Group  4  124.000  51.000  42.848  205.152
CARM  Standard of Care Ethanol Lock Therapy Group  8  208.000  151.000  81.761  334.239

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and identifies 4 secondary outcomes as posted. It reports no analyses. The record does not describe a multiplicity strategy, such as whether one outcome was designated as the sole confirmatory test or whether the chance of false-positive findings across multiple outcomes was controlled. Without reported inferential tests, no claim about statistically significant findings across outcomes can be assessed.

Missing-data handling is not reported in the registry record. It is not clear whether all randomized participants had a recorded LOS, how incomplete outcome information was handled, or whether any participants were excluded from the primary outcome summaries. The outcome is described for confirmed CRI cases, but the record does not explain how confirmation was determined for analysis or how participants without a confirmed case were treated.

The analysis population is also not reported in the registry record. There is no statement about whether the primary analysis followed intention-to-treat principles, included only participants who received the assigned timing strategy, or used another population definition. The registry’s outcome title refers to 14 confirmed cases, while the arm summaries report counts of 4 and 8. It also notes a participant with 2 distinct episodes enrolled twice in each group, without explaining how these observations entered the analysis. These details prevent a clear account of the denominator and unit of analysis.

Randomization, missing outcome data, analysis population and repeated observations all affect interpretation of a treatment comparison. The registry record does not provide enough information to determine how these issues were addressed. The posted descriptive results should not be treated as a complete statistical analysis.

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 0% reporting threshold.

The registry reports serious adverse events for the two arms. In Arm 1, 0 serious adverse events are listed among 4 participants at risk; in Arm 2, 0 are listed among 8 participants at risk. Deaths are reported as 0 in both arms. The registry also lists 0 other adverse events among 4 participants at risk in Arm 1 and 0 among 8 at risk in Arm 2. No serious adverse event terms are listed.

These are event counts in the recorded safety groups, not an estimate of the probability of future harm. Zero reported events in these groups does not establish that no adverse events occurred outside the registry’s reported categories or observation period, and small groups provide limited information about uncommon events. The record does not give detailed definitions, event narratives, severity grading beyond the serious category, or exposure-adjusted safety analyses.

Safety counts should be interpreted separately from the LOS outcome. They do not explain the difference between the posted mean stays and cannot establish the comparative safety of the timing strategies. The registry record does not report further safety analyses or a detailed account of how adverse events were collected.

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

The registry’s primary outcome summaries show mean LOS of 124.0 hours in the pre-emptive ELT group and 208.0 hours in the standard-care ELT group, with standard deviations of 51.0 and 151.0, respectively. This is a descriptive comparison among the cases represented in the posted outcome summaries. The registry record does not report a confidence interval, p-value, or statistical test for the comparison, so its precision is not quantified.

The results do not establish that early timing caused shorter stays. Although the trial is described as randomized, the outcome counts and episode accounting are not fully explained, and the analysis population and analysis methods are not reported. The unblinded design may also matter for outcomes involving discharge timing. No adjustment or sensitivity analysis addressing these issues is reported in the registry record.

The posted primary measure is total LOS, not the separately defined ALOS that was intended to count hospital days attributable to CRI. No ALOS result is reported in the registry record. The LOS summaries therefore should not be described as the number of days caused by infection, nor as a direct estimate of catheter sterilization, catheter salvage or re-infection.

The registry lists secondary outcomes for catheter sterilization, catheter salvage, adverse events per episode and re-infection, but does not report their analysis results. The safety record lists no serious adverse events or deaths in the stated groups, but those counts do not rule out events not represented in the record or provide precise estimates of uncommon risks.

In short, the posted data describe the arm-level LOS means and variability and show a shorter observed mean in the pre-emptive group. They do not quantify the uncertainty of the comparison, resolve the outcome-count discrepancy, or support a broad conclusion about treatment effect. Further interpretation would require a clear account of the analyzed episodes, the prespecified statistical approach and the full outcome results.

14. Why This Trial Matters Statistically

This trial raises statistical issues that commonly arise when a clinical outcome is recorded over infection episodes rather than only once per participant. The registry notes that a participant with 2 distinct catheter infection episodes was enrolled twice in each group. Repeated observations from the same person may share characteristics, so treating them as independent can understate uncertainty. Clear reporting of the analysis unit and any approach to within-participant dependence is important for interpreting the precision of an estimate. Those details are not reported in the registry record.

The outcome is also framed in two related but distinct ways. Total LOS measures the duration of hospitalization, while ALOS is defined by the time from first symptoms or admission to the first negative blood culture. The distinction matters because a total stay can include time unrelated to infection. Although the record describes both outcomes, it posts primary LOS summaries and does not report an ALOS result.

The group means have visibly different reported variability: the standard deviations are 51.0 and 151.0 hours. Unequal variability and potentially skewed LOS observations can affect how a comparison should be modeled. The reported means alone do not show whether a simple normal approximation is appropriate. The registry does not report diagnostics or an inferential method.

Finally, the small outcome counts and absence of a posted treatment comparison highlight the difference between a descriptive result and a precise estimate. A randomized design is valuable, but interpretation still depends on transparent reporting of the outcome population, missingness, repeated episodes and uncertainty. The record’s limitations make those statistical details especially important to readers assessing the observed arm summaries.

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 primary outcome is reported only through arm-level means, standard deviations and counts. The registry record does not provide individual observations, confidence intervals, a p-value, or a statistical test. It also does not report an adjusted analysis or a clear account of the model used. The observed mean difference in direction is therefore not accompanied by a quantified measure of uncertainty.

There is ambiguity in the outcome population. The primary outcome title refers to 14 confirmed catheter-related infection cases, whereas the outcome arm counts are 4 and 8. The record notes a participant with 2 distinct infection episodes enrolled twice in each group, but does not explain the relation between those statements or how episodes were represented in the analysis. The counts should not be combined or treated as a clearly defined participant total without further information.

The registry does not report how missing outcome data were handled, the analysis population, or whether every randomized participant was included in the primary analysis. It does not report the randomization sequence, allocation concealment, baseline characteristics, protocol deviations, or treatment adherence. As an unblinded study, care decisions and discharge timing could be influenced by knowledge of assignment; the record does not explain whether such influences were assessed.

LOS is a broad measure and is not interchangeable with the defined ALOS. Although the study description identifies ALOS as an outcome, no ALOS result is posted. Secondary outcomes are listed, but their results are not reported in the registry record. Safety summaries contain zero reported events in the listed categories, without detailed event definitions or exposure information. Together, these gaps limit assessment of precision, generalizability and the completeness of the posted findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection — NCT02095951.
• Registry record last updated 2018-12-19; status last verified 2018-08.
• Results first posted 2018-12-19.
• 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.

19. Record Summary

NCT02095951 is a completed Phase 4 randomized, unblinded, parallel trial at Children's Hospital of Michigan. It compared pre-emptive ELT with ELT given at the first positive blood culture report, both with systemic antibiotics, in pediatric patients with central catheters and suspected or proven CRI. The registry lists enrollment of 30 and study dates of 2014-06 to 2016-06.

The primary outcome is LOS in confirmed catheter-related infection cases. The posted means are 124.0 hours in the pre-emptive group and 208.0 hours in the standard-care group, with standard deviations of 51.0 and 151.0. No inferential comparison is reported. The record also notes repeat enrollment for distinct episodes but does not fully explain the outcome population or analysis unit. ALOS and the listed secondary outcome analyses are not reported in the registry record.