Efficacy and Safety of BIO-K + CL1285 in Prevention of Antibiotic-associated Diarrhea in Hospitalized Adult Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of BIO-K + CL1285 in Prevention of Antibiotic-associated Diarrhea in Hospitalized Adult Patients (NCT00328263), a randomized phase 3 study. The primary outcome is The Incidence of Antibiotic-associated Diarrhea..

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Its official title describes adults exposed to nosocomial infection; the study summary says its purpose was to evaluate the efficacy and safety of Bio-K+ CL1285 versus placebo for prevention of antibiotic-associated diarrhea in hospitalized adult patients. The registry lists 472 participants enrolled.

The intervention arm was Bio-K+ CL1285, described as a dietary supplement containing 50 billion of live bacteria. The registry names Lactobacillus acidophilus CL1285 and Lactobacillus casei. The comparator was a dietary-supplement placebo described as devoid of bacteria. The registry identifies the study as double-blind but does not describe the masking procedures, allocation ratio, sequence-generation method, or concealment process. Those details are not reported in the registry record.

The listed study dates are 2006-03 for study start and 2007-03 for primary completion; the status is completed. The primary outcome was the incidence of antibiotic-associated diarrhea, recorded as a number of participants, with a timeframe of up to 40 days. The endpoint description refers to at least one diarrhea episode within 24 hours, but does not clarify how that interval relates to the full follow-up timeframe.

Secondary outcomes concerned positive Clostridium difficile toxin A or B results in patients with antibiotic-associated diarrhea, health outcomes and direct medical costs under alternative prevention strategies, and the safety profile of Bio-K+ CL1285 versus placebo in patients on antibiotics. The registry lists three secondary outcomes. It does not report the detailed methods for measuring or analyzing them.

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: Inclusion \& exclusion criterias were used to randomized patients. Patients were followed for an additionnal 21 days after treatment ended.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as The Incidence of Antibiotic-associated Diarrhea., measured over Up to 40 days.

The primary endpoint is titled the incidence of antibiotic-associated diarrhea and is measured as a number of participants. Its description defines the event as the presence of at least one diarrhea episode within 24 hours, with a stated observation timeframe of up to 40 days. In a prevention study, an incidence endpoint can describe how many participants experience the event during the specified observation period. It can therefore distinguish participants with an event from those without one, provided both categories are clearly recorded.

The posted arm values are 216 for Bio-K+ CL1285 and 221 for placebo, and the corresponding arm sizes are also 216 and 221. The comparison likewise records 216 events among 216 participants and 221 among 221. The registry record does not explain whether these values represent event counts, the full analysis population, or a reporting limitation. As posted, they do not show a contrast between participants with and without diarrhea.

The event definition and timeframe matter for interpretation. The record gives “within 24 hours” as the episode criterion and “up to 40 days” as the timeframe, but does not explain when the episode must occur within follow-up, how episodes were ascertained, or how recurrent episodes were handled. These measurement details are not reported in the registry record.

7. Results Posted in the Registry

• Bio-K+ CL1285: 100.0% (216/216) versus 100.0% (221/221) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary in concept: each participant either experienced the defined diarrhea event during the observation period or did not. The registry describes the result as a number of participants and lists a risk difference as the comparison measure. A risk difference expresses the difference between the event proportions in two groups. Its interpretation depends on having valid event and denominator counts for both groups. The record reports arm sizes of 216 and 221, and event counts of 216 and 221, respectively, but does not explain this complete alignment.

What the comparison statistics represent

The posted risk difference is 0.0, with limits of 0.0 and 0.0. The reported proportions are 1.0 in each arm, and the reported ratio is 1.0, with limits of 1.0 and 1.0. The p-value is 1.0. These values are internally consistent with identical proportions as represented in the record. They do not resolve whether the outcome counts accurately represent the defined clinical event, because the registry does not explain the apparent classification of every listed participant as an event.

General statistical explanation: a p-value describes how compatible the observed data are with a specified null model, subject to the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of a result. A p-value of 1.0 is the value posted for this comparison, but the registry does not report the test used, its assumptions, or whether the analysis was adjusted for any other variables.

Why the event counts matter

For a binary outcome, the event count and the number of participants evaluated determine the observed event proportion. When the event count equals the denominator in both groups, the submitted comparison represents identical proportions. In this record, that numerical pattern prevents readers from identifying a non-event count from the primary outcome results. The registry does not say whether the values were intended to be counts of participants with diarrhea, counts of all participants in an outcome set, or something else. The record’s stated outcome definition cannot settle that ambiguity.

General statistical explanation: the risk difference is an absolute measure, in contrast with a ratio measure that compares proportions relative to one another. Both can be useful, but their interpretation relies on correct outcome coding and denominators. When outcome counts or analysis populations are unclear, the apparent precision of either measure may be misleading. No adjusted estimate, model specification, or sensitivity analysis is reported in the registry record.

What is not documented

The registry identifies the study as randomized, double-blind, parallel-group, and placebo-controlled. It does not report the randomization sequence method, allocation concealment, a statistical analysis plan, the test used for the primary comparison, or any covariate-adjustment strategy. It also does not report whether the analysis followed intention-to-treat, per-protocol, or another population definition. These methods cannot be inferred from the trial design labels alone.

The record describes the endpoint as at least one diarrhea episode within 24 hours and gives a timeframe of up to 40 days. It does not specify how investigators confirmed an episode, how outcome data were collected, how repeated episodes were treated, or how participants who stopped treatment or left follow-up were handled. Missing-data methods are not reported in the registry record. Without such details, the statistical result cannot be assessed for sensitivity to outcome classification or missingness.

Planning and power

General statistical explanation: a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability or event frequency, significance level, power, and allocation. It is distinct from an analysis of observed outcomes. The record does not report the trial’s own sample-size justification or target assumptions. Planning illustrations based on an observed effect are not observed power and should not be interpreted as evidence about whether the trial was adequately powered. The planning description specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation; it does not make these the documented original design assumptions.

For binary outcomes, the suitability of a normal approximation depends on the information in the event counts and the analysis method. General statistical explanation: when counts are sparse or outcomes are highly concentrated, approximation-based methods may not represent uncertainty well. In this case, the record’s event-count ambiguity prevents a meaningful assessment of that issue. The registry also does not report interim analyses, multiplicity procedures, or a method for handling the listed secondary outcomes. Those elements are not reported in the registry record.

10. Confidence Intervals and Precision

The posted primary comparison has a risk difference of 0.0 and confidence limits of 0.0 and 0.0. The reported ratio is 1.0, with limits of 1.0 and 1.0. Those intervals have no displayed width. The registry does not identify the confidence-interval method or explain why the reported limits coincide with the point estimates.

General statistical explanation: a confidence interval represents uncertainty in an estimate under a specified statistical procedure and its assumptions. A narrow interval can indicate a precise estimate when the outcome data and method are appropriate. However, an interval’s numerical width is not enough to establish that the underlying measurement is valid or that the analysis is suitable. Here, the counts equal the listed group sizes, and the record does not clarify whether those counts represent participants who experienced the stated endpoint. The apparent exactness should therefore be interpreted with caution.

The arm counts are 216 for Bio-K+ CL1285 and 221 for placebo. The registry lists 472 participants enrolled, but does not explain how the enrollment figure relates to the participants included in the outcome counts. It does not report the number with missing primary outcomes, the analysis population, or a missing-data method. These omissions make it difficult to judge how completely the endpoint was observed.

The confidence limits are registry-reported values, not a guarantee that all plausible clinical differences have been ruled out. The record does not report a clinically meaningful margin or an equivalence framework. Nor does it provide enough information to reconstruct an alternative uncertainty estimate from clearly classified event and non-event counts. The displayed precision is therefore a property of the submitted comparison, while the underlying precision of the clinical endpoint remains difficult to evaluate from the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: positive Clostridium difficile toxin A or B results among patients with antibiotic-associated diarrhea; health outcomes and direct medical costs for alternative prevention strategies; and the safety profile of Bio-K+ CL1285 versus placebo in patients on antibiotics. It does not provide posted analyses for these outcomes in the record. The record lists four outcome measures overall, but does not give details sufficient to identify how each measure was analyzed.

Multiplicity arises when several outcomes, comparisons, or analysis choices are assessed. General statistical explanation: examining multiple results can increase the chance that at least one appears notable by chance, so a prespecified approach may be used to control or interpret that risk. Whether any such adjustment or hierarchy was used is not reported in the registry record. The record also does not state whether the secondary outcomes were prespecified in a statistical analysis plan or how their results were intended to be interpreted alongside the primary outcome.

The primary outcome counts are reported as 216 of 216 and 221 of 221. The record does not clarify whether all enrolled participants were eligible for this analysis, whether any outcomes were missing, or whether a particular analysis population was used. The enrolled total is 472, and the registry does not explain its relationship to the arm counts. It does not report how participants with incomplete follow-up, protocol deviations, or discontinued treatment were handled.

General statistical explanation: missing outcome data can affect an estimate when the probability of being observed is related to the outcome or differs between groups. Appropriate interpretation depends on knowing how much data are missing and what assumptions or methods were used. Neither the amount of missing primary-outcome data nor the method for addressing it is reported in the registry record. The record also does not report interim analyses or stopping rules. These gaps limit assessment of the full analysis strategy.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: serious adverse events (10.4%).

The safety results list serious adverse events for 15 of 216 participants in the Bio-K+ CL1285 group and 23 of 221 participants in the placebo group. The registry separately lists other adverse events for 109 of 216 and 113 of 221 participants, respectively. The displayed serious-adverse-event term is 10.4%. The registry does not provide a death count for either group.

These figures are descriptive counts. They do not, on their own, establish whether the groups differ in safety, whether an event was caused by the intervention, or whether the types and severity of events were comparable. The record does not give event-level descriptions for the listed serious-event counts, definitions or ascertainment details, follow-up duration specific to safety, or a statistical comparison. Those details are not reported in the registry record.

General statistical explanation: safety comparisons require attention to the number of participants at risk, how events were defined and collected, and the amount of time under observation. Counts alone do not describe all those features. The serious-event figures should be read as the registry’s reported participant counts, not as a complete causal assessment.

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

The registry records a randomized, double-blind comparison of Bio-K+ CL1285 with placebo for prevention of antibiotic-associated diarrhea in hospitalized adults. Its primary comparison reports a risk difference of 0.0, a confidence interval from 0.0 to 0.0, and p = 1.0. The reported proportions and ratio are also identical between arms. These statistics describe the comparison as submitted, but the record does not make the clinical meaning of the underlying outcome counts clear.

The main interpretive issue is that the primary outcome values match the arm sizes: 216 of 216 for Bio-K+ CL1285 and 221 of 221 for placebo. If read literally as participants with at least one diarrhea episode, the record would classify everyone in both groups as having the event. Yet it does not clarify whether this was the intended meaning of those values. It would be inappropriate to treat the zero difference as a definitive conclusion about the incidence of diarrhea without resolving that ambiguity.

A result with no detected difference is not automatically evidence that two treatments are equivalent. A conclusion of equivalence requires an appropriate design and a prespecified margin, neither of which is reported in the registry record. Likewise, the posted p-value is not a measure of the probability that the treatments are the same, and the zero-width confidence interval should not be understood as certainty about the true clinical effect.

The registry does show that serious adverse events were recorded in both groups, with counts of 15 and 23, and that other adverse events were also recorded. Those counts alone do not establish a causal relationship or provide a complete comparative safety assessment. The record’s limited detail on outcome classification, analysis populations, missing data, and statistical methods restricts how far either the efficacy or safety results can be interpreted.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why numerical summaries must be checked against the outcome definition and denominators. The primary outcome is described as the number of participants with antibiotic-associated diarrhea, but the posted counts equal the number of participants listed in each arm. That pattern produces identical proportions and a zero risk difference in the registry comparison. Without a clear account of what the counts represent, the apparent agreement between the groups cannot be given a confident clinical interpretation.

The record also illustrates the distinction between an estimate and the information needed to judge its precision. It reports a confidence interval with identical lower and upper limits, but does not state the method used to calculate it. General statistical explanation: confidence limits are useful only in the context of the data and assumptions that generated them. A very narrow interval cannot compensate for uncertainty about outcome coding, denominators, or the analysis population.

Other important statistical reporting elements are absent, including the original sample-size justification, analysis plan, missing-data methods, and multiplicity approach. Their absence does not show that the study lacked such procedures; it means they are not reported in the registry record. That distinction matters when readers assess what conclusions the posted results can support.

The trial’s randomized, double-blind, placebo-controlled design establishes the intended comparison structure, while the posted outcome information limits interpretation of the primary result. Reading both together is a useful reminder that design labels and precise-looking estimates do not replace transparent reporting of event counts, denominators, and analysis methods.

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 central limitation in interpreting this trial’s primary result is the alignment of the outcome counts with the arm sizes: 216 of 216 in the Bio-K+ CL1285 group and 221 of 221 in the placebo group. The registry does not clarify whether those values represent participants who experienced diarrhea, all participants in an analysis set, or another quantity. This leaves the endpoint’s observed event classification uncertain.

The registry lists 472 enrolled participants but does not explain the relationship between that figure and the primary outcome counts. It does not report an analysis population, participant flow, missing outcome counts, or a method for handling missing data. As a result, the completeness of follow-up and the denominators underlying the comparison cannot be fully assessed.

The endpoint description combines an event criterion of at least one diarrhea episode within 24 hours with a timeframe of up to 40 days. The record does not explain how the episode criterion was applied during the stated timeframe, how diarrhea was assessed, or whether recurrent episodes were relevant. The treatment schedule and duration are also not reported in the registry record.

Further limitations are the absence of a reported statistical analysis plan, primary-test method, confidence-interval method, sample-size justification, multiplicity approach, and interim-analysis information. The registry identifies the study as randomized and double-blind but does not provide procedural details for randomization or masking. These omissions constrain assessment of potential bias and the reliability of the statistical analysis; they do not establish that the procedures were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of BIO-K + CL1285 in Prevention of Antibiotic-associated Diarrhea in Hospitalized Adult Patients — NCT00328263.
• Registry record last updated 2014-08-07; status last verified 2014-07.
• Results first posted 2014-08-07.
• 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

NCT00328263 is a completed phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter study sponsored by Bio-K Plus International Inc. The registry lists 472 participants enrolled, with a start date of 2006-03 and primary completion in 2007-03. It evaluated Bio-K+ CL1285, described as containing 50 billion of live bacteria, against a placebo described as devoid of bacteria.

The primary outcome was the incidence of antibiotic-associated diarrhea, measured as a number of participants, over up to 40 days. The posted arm counts are 216 of 216 for Bio-K+ CL1285 and 221 of 221 for placebo. The comparison reports a risk difference of 0.0, confidence limits of 0.0 to 0.0, and p = 1.0. The registry does not clarify the meaning of counts equal to the arm sizes, limiting interpretation of the primary result.

Three secondary outcomes concern Clostridium difficile toxin results, health outcomes and medical costs, and safety. Serious adverse-event counts are 15 and 23 in the Bio-K+ CL1285 and placebo groups, respectively. Details on the analysis plan, missing data, and secondary-outcome analyses are not reported in the registry record.