Chlorhexidine Gluconate Cleansing in Preventing Central Line Associated Bloodstream Infection and Acquisition of Multi-drug Resistant Organisms in Younger Patients With Cancer or Undergoing Donor Stem Cell Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Chlorhexidine Gluconate Cleansing in Preventing Central Line Associated Bloodstream Infection and Acquisition of Multi-drug Resistant Organisms in Younger Patients With Cancer or Undergoing Donor Stem Cell Transplant (NCT01817075), a randomized phase 3 study. The primary outcome is Central Line-associated Bloodstream Infections (CLABSI) Events During the At-risk Days.

2. Clinical Question

3. Trial Design

The registry identifies NCT01817075 as a phase III randomized trial with a parallel design and double masking. The sponsor was Children's Oncology Group. Enrollment was 177, and the registry status is completed. The recorded start date is 2013-11-04, with primary completion on 2019-03-31. These registry descriptors do not, by themselves, establish how allocation concealment or masking procedures were carried out.

The trial studied CHG cleansing in children with cancer or those receiving allogeneic hematopoietic cell transplantation. Arm I received CHG cleansing wipes, and Arm II received control cleansing wipes. Both arms were scheduled to use topical skin wipes QD for 90 days. The intervention list also names a mild soap skin cleanser, laboratory biomarker analysis, and questionnaire administration; the record does not provide further operational detail about those activities in the outcome information.

The primary endpoint was CLABSI events per 1000 at-risk days, assessed up to 90 days post enrollment date. The registry defines eligible at-risk days as days when eligible central lines were in place and states that CLABSI followed the January 2015 Centers for Disease Control and Prevention criteria. The reported arm counts for the primary endpoint are 88 for CHG and 86 for control. The analysis population description says 3 patients were excluded, leaving 174 in the analyses.

There are four posted outcome measures and no reported analyses. The registry record does not report the allocation sequence method, concealment procedure, masking details, or a full statistical analysis plan. It also does not report the trial's original sample-size justification or whether interim analyses were planned or conducted. Those omissions limit what can be concluded about the trial's prespecified analytical framework.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 3 patients were excluded (2 ineligible and 1 withdrew consent) leaving 174 patients in the analyses.

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 Central Line-associated Bloodstream Infections (CLABSI) Events During the At-risk Days, measured over Up to 90 days post enrollment date.

The primary endpoint counts CLABSI events and expresses them as a rate per 1000 at-risk days, up to 90 days post enrollment date. At-risk days are days with eligible central lines in place. This denominator is intended to reflect the time during which patients had an eligible central line and were therefore being observed for the endpoint, rather than treating all follow-up time as equivalent. The registry states that CLABSI was defined according to the January 2015 Centers for Disease Control and Prevention criteria.

A rate endpoint is useful when the amount of time at risk can differ across participants or arms. In general, expressing event counts relative to time at risk can make comparisons more interpretable than counts alone, because it accounts for the period during which an event could be observed. The rate still depends on the endpoint definition, ascertainment, and completeness of at-risk time. Those details matter particularly when central lines may not be present for the same duration for every participant.

The posted primary results report a rate and 95% confidence interval for each arm: 5.44 CLABSI per 1000 at-risk days for CHG, with a 95% confidence interval of 3.62 to 8.18; and 3.1 for control, with a 95% confidence interval of 1.82 to 5.28. The record does not provide an estimable two-arm comparison for this count-type outcome. The arm-specific estimates therefore describe the posted rates, but do not alone establish the size or uncertainty of a direct treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome types determine which statistical summaries are most natural. The primary endpoint counts CLABSI events over at-risk time, while two posted secondary outcomes are percentages of patients. A rate, a percentage, and a direct arm-to-arm contrast answer related but different questions. Keeping those distinctions clear helps avoid treating every number as if it measured the same quantity.

What does the primary rate describe?

The primary endpoint is reported as CLABSI per 1000 at-risk days. Its numerator is the count of CLABSI events, and its denominator is eligible time at risk, defined in the record as days with eligible central lines in place. In general, a rate accounts for differing amounts of observation time by relating events to time at risk. It is not the same as the proportion of participants who experienced an event; a participant can contribute different amounts of at-risk time, and the rate summary is constructed around that exposure time.

The registry posts an estimated rate for each arm and a 95% confidence interval for each estimate. In general, the interval conveys the sampling uncertainty associated with the estimated rate under the method used. Wider intervals indicate less precision than narrower intervals, though interval width also depends on the event process and analysis assumptions. The registry record does not state the specific model or method used to obtain the primary rate intervals. It also does not provide a direct arm contrast for this endpoint. Consequently, no formal comparison of the two rates can be recovered from the posted arm summaries alone without making additional assumptions.

What does a risk difference mean?

For the binary secondary outcomes, the posted recalculated comparisons use a risk difference. In general, a risk difference is the estimated percentage-point contrast between the event proportions in two groups, expressed on the probability scale. A value above zero indicates a higher observed proportion in the intervention group under the stated orientation; a value below zero indicates a lower proportion. The confidence interval describes uncertainty around that contrast. If the interval spans zero, the data are compatible with no difference as well as with differences in either direction at the confidence level represented by the interval.

The recalculated comparisons are unadjusted, simple re-calculations from posted summary statistics. They are not reported sponsor analyses. The MDRO comparison has a risk difference of 0.031 and a 95% confidence interval from -0.069 to 0.132, with unadjusted p = 0.54. The reduced-susceptibility comparison has a risk difference of 0.123 and a 95% confidence interval from 0.014 to 0.231, with unadjusted p = 0.024. The risk ratios and odds ratios also appear in the posted comparison summaries, but those are alternative scales for the same binary endpoint comparisons and should not be mistaken for primary-endpoint analyses.

A p-value measures how incompatible the observed data are with a specified null model, assuming the model and analysis conditions hold. In general, an unadjusted p-value does not express the probability that a null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry record does not report sponsor analyses for these comparisons, and the recalculated p-values do not account for any multiplicity across the several outcomes. Their evidential weight is therefore limited.

Why do event counts need care?

Count outcomes can show over-dispersion when the observed variability exceeds that expected under a simple count model. In general, over-dispersion can make standard errors too small if the analysis assumes less variability than the data contain. A method that allows for extra variation can produce more appropriate uncertainty estimates. The registry record does not report whether over-dispersion was assessed or what count model, if any, was used for the primary rate. The posted interval should therefore be interpreted as an outcome summary without assuming an unreported model specification.

The primary outcome's analysis population description records 3 exclusions—2 ineligible and 1 withdrew consent—and states that 174 patients remained in the analyses. Arm sizes for the primary results are 88 and 86. The registry does not explain how missing at-risk time, any incomplete outcome ascertainment, or other protocol deviations were handled. Those details can affect both rate estimation and the uncertainty around it.

What do the planning illustrations mean?

The sample-size illustrations are planning estimates derived from observed effects, not the trial's own design justification. The record states that they assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect set to a stated fraction of the observed effect. In general, such calculations show how a hypothetical future study's size may change when the target effect is smaller or larger. They are not observed power, do not describe the actual power of this completed trial, and do not establish that the original trial was designed using those assumptions.

The planning illustrations for binary outcomes are stated as participants per arm. The record notes that time-to-event calculations, when present, instead give total events; the posted outcomes do not provide a time-to-event comparison. The original sample-size assumptions and justification are not reported in the registry record. Readers should therefore keep the illustrative calculations separate from the actual trial design and from the observed endpoint results.

10. Multiplicity, Missing Data and Analysis Populations

The record lists four outcome measures, including the primary CLABSI endpoint and secondary outcomes concerning MDRO, reduced CHG susceptibility, and bacteremia. It reports no analyses. For the binary secondary outcomes, the posted comparison statistics are unadjusted re-calculations from the summary results, not reported sponsor analyses. The registry record does not report whether a formal testing hierarchy, family of hypotheses, multiplicity adjustment, or prespecified distinction between confirmatory and exploratory outcomes was used.

This omission matters because interpreting each secondary p-value in isolation can overstate the strength of evidence when several outcomes are assessed. In general, multiplicity procedures set out how inference will account for the number and relationship of tests. Different procedures answer different inferential goals, and no particular method should be assumed when it is not documented. The reported unadjusted secondary p-values therefore do not have a stated adjustment for the other outcomes in the record.

Missing-data handling is also not reported in the registry record. The primary endpoint description says that 3 patients were excluded—2 ineligible and 1 withdrew consent—and that 174 patients remained in the analyses. It does not describe any additional exclusions, how missing observations or at-risk time were handled, or whether participants were analyzed according to randomized assignment. Reasons for the differing endpoint-specific denominators are not reported in the registry record.

The analysis population information is consequently incomplete for evaluating potential bias. For instance, the record does not specify how outcome ascertainment was handled when a participant had incomplete follow-up, whether sensitivity analyses were conducted, or how deviations from assigned cleansing were treated. These are not evidence that the analyses were deficient; they are information gaps that prevent a reader from assessing those aspects of the analysis. The record also does not report the statistical analysis plan, so the prespecification of the posted endpoints and comparisons cannot be verified from the registry information.

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: cardiac arrest (1.2%), multi-organ failure (1.2%).

The posted safety information records serious adverse events affecting 0 participants in the CHG arm and 2 in the control arm. Other adverse events are recorded for 22 participants in the CHG arm and 14 in the control arm. Deaths are recorded for 1 participant in the CHG arm and 3 in the control arm. These are descriptive counts in the registry record; they do not establish that cleansing caused or prevented any event.

The top serious adverse event terms listed are cardiac arrest and multi-organ failure, each reported as 1.2%. The registry information does not identify an arm for these top terms in the provided listing, so they should not be attributed to either group. It also does not provide detailed event narratives, timing, relatedness assessments, or a comparative safety analysis.

Adverse-event counts require context, including ascertainment rules, exposure time, severity classification, and whether events were judged related to an intervention. Those details are not reported in the registry record. The counts should therefore be read as a limited descriptive account, not as a complete assessment of comparative safety or as evidence of causation.

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

The posted data describe a randomized, double-masked, parallel phase III trial of CHG cleansing wipes versus control cleansing wipes in children with cancer or receiving allogeneic hematopoietic cell transplantation. The primary outcome is a CLABSI rate per 1000 at-risk days, with arm-specific estimates and confidence intervals. The registry does not provide an estimable direct comparison for that count-type endpoint. As a result, the record supports description of each arm's posted rate, but not a precise registry-reported estimate of the difference between arms.

The secondary outcomes add information about MDRO, reduced CHG susceptibility, and bacteremia. The binary endpoint comparisons were recalculated from posted summaries and are unadjusted. They are not reported sponsor analyses, and no multiplicity strategy is documented. These results may help readers understand the observed pattern, but they do not settle the primary question or establish a comprehensive account of the trial's outcomes.

In general, a randomized design can support comparisons between assigned groups when the analysis and follow-up are appropriately conducted. However, the registry record does not provide enough detail about the allocation process, analysis populations, missing-data handling, or statistical methods to evaluate all those conditions. The distinction between an arm-specific outcome summary and a direct comparison remains essential: an estimate in one arm and an estimate in another do not, by themselves, supply the contrast and uncertainty needed for a formal inference.

The record also does not report the study's sample-size justification or original analysis plan. The posted planning calculations are illustrations based on observed effects and stated assumptions, not evidence of the trial's design rationale or observed power. Without those design details, readers should avoid treating the calculations as confirmation that the trial was sized for a particular clinically meaningful effect.

Accordingly, the registry information describes outcomes observed and posted for this trial, along with important limits on interpretation. It does not establish that CHG cleansing works or does not work, and it does not support medical advice. Conclusions about effects would require a complete analysis with transparent methods, direct estimates for the primary comparison, and appropriate consideration of uncertainty, multiplicity, missing data, and outcome definitions.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a rate tied to time at risk, rather than a simple count or proportion. The denominator depends on eligible central-line time, so interpretation involves both infection events and the time participants were under observation with eligible lines in place. That structure makes a direct, clearly specified rate comparison especially important.

The registry posts separate estimates and confidence intervals for the CHG and control arms, but no estimable two-arm comparison for the primary count-type endpoint. This illustrates a broader statistical point: arm summaries can describe the data, yet they do not always contain enough information to reconstruct an appropriate contrast. A reader needs the comparative estimate and its uncertainty to evaluate how compatible the observations are with differing underlying rates.

The trial also includes secondary outcomes with different measurement scales. Percentages of patients with organism outcomes answer questions about the proportion affected, while an at-risk-time rate summarizes event occurrence relative to observation time. Their results should not be combined as though they were repeated measurements of the same endpoint. The unadjusted recalculations further demonstrate why statistical significance and evidential strength are not identical, particularly when the registry does not report multiplicity control or sponsor analyses.

Finally, the record illustrates the value of transparent analysis documentation. Information about the analysis plan, missing data, endpoint-specific denominators, and primary comparison methods would help readers distinguish prespecified inference from exploratory recalculation. Without those details, the posted numbers remain useful descriptive evidence, but their inferential scope is limited.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. The primary CLABSI endpoint is reported as separate arm-level rates and confidence intervals, without an estimable two-arm comparison. The registry record does not identify the model or method used to calculate the primary intervals, or explain why the count-type comparison could not be estimated. The result is therefore less informative about the comparative effect than a direct estimate with its uncertainty would be.

The analysis population description notes 3 exclusions and says 174 patients remained in the analyses, but does not describe the broader handling of incomplete outcome data or at-risk time. The record also does not explain why the denominators differ across secondary outcomes. Without that information, the possibility and implications of missing outcome data cannot be assessed from the registry entry alone.

For the secondary binary outcomes, the comparisons are recalculated from posted summary statistics and are unadjusted; no sponsor analyses are reported. No multiplicity procedure is documented, and the record does not identify a prespecified testing hierarchy. These omissions weaken the basis for treating an isolated secondary result as confirmatory. The bacteremia outcome is listed, but a reported analysis is not available in the record.

Other design and analysis details are also absent: the allocation sequence and concealment methods, masking procedures, the statistical analysis plan, the sample-size justification, and whether interim analyses occurred are not reported in the registry record. These omissions do not prove that the procedures were absent; they limit what can be assessed from the available entry. The registry also provides limited safety detail, with no event narratives or comparative safety analysis. Finally, the results concern the described pediatric cancer and transplant population and cannot automatically be extended to populations not specified in the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Chlorhexidine Gluconate Cleansing in Preventing Central Line Associated Bloodstream Infection and Acquisition of Multi-drug Resistant Organisms in Younger Patients With Cancer or Undergoing Donor Stem Cell Transplant — NCT01817075.
• Registry record last updated 2021-06-22; status last verified 2020-03.
• Results first posted 2020-04-08.
• 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

NCT01817075 is a completed phase III randomized, double-masked, parallel trial sponsored by Children's Oncology Group. It enrolled 177 and compared CHG cleansing wipes with control cleansing wipes, used QD for 90 days, in children with cancer or receiving allogeneic hematopoietic cell transplantation.

The primary endpoint was CLABSI events per 1000 at-risk days up to 90 days post enrollment date. The record reports arm-specific rates and 95% confidence intervals, but no estimable two-arm comparison for this endpoint. Secondary outcomes include MDRO, reduced CHG susceptibility, and bacteremia. The record reports no sponsor analyses; available binary comparisons are unadjusted re-calculations. The original analysis plan, multiplicity approach, missing-data methods, and sample-size justification are not reported in the registry record.