Effects of Antibiotic Prophylaxis on Recurrent UTI in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Antibiotic Prophylaxis on Recurrent UTI in Children (NCT02357758), a non-randomized phase 4 study. The primary outcome is Changes to the Urinary Microbiota.

2. Clinical Question

3. Trial Design

This is a Phase 4, non-randomized, parallel study marked as completed. Total enrollment is 59. The record gives a start date of 2012-09 and a primary completion date of 2016-01. It describes three groups: patients with RUTI receiving antibiotic prophylaxis, patients with RUTI under clinical observation, and a healthy population.

Treatment assignment was not randomized. For patients with RUTI, whether prophylaxis was used was determined by the clinician. The registry record describes the prophylaxis options as Septra (Trimethoprim dose 2mg/kg) or nitrofurantoin (dose 2 mg/kg). It does not report a masking procedure; masking is listed as none. These features matter when interpreting comparisons: treatment groups may differ in ways related to clinical decisions or participant characteristics, independently of treatment.

The primary outcome concerns changes to the urinary microbiota, measured through urine culture at baseline and 3-, 6-, 9-, and 12-months. Other listed outcomes concern metabolic profiles of urine, antibiotic susceptibility, and pro-inflammatory cytokines. The record does not report detailed eligibility criteria, group-specific enrollment totals, or a statistical analysis plan. It also does not report numerical outcome results or analyses. The completed status therefore describes the study’s registry status, but does not by itself establish that every planned measurement or analysis was completed or reported.

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

Analysis population for the primary outcome, as defined in the registry: Bacterial culture data was not available for all participants due to the low volume of some samples.

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 Changes to the Urinary Microbiota, measured over Baseline, 3-, 6-, 9-, 12-months.

The primary endpoint is titled Changes to the Urinary Microbiota. The registry describes it as changes in colony forming units (CFUs) for Enterococcus sp., Escherichia coli, Klebsiella sp./Enterobacter sp., Staphylococcus saprophyticus, or Pseudomonas sp./Staphylococcus aureus in urine cultured on CHROMagar Orientation. The stated observation times are baseline and 3-, 6-, 9-, and 12-months.

The record says the data were analyzed in terms of bacterial counts, presence or absence, and presence at or above the diagnostic threshold for UTI: 10^5 CFU/mL of one species. The endpoint description focuses the posted primary measure on participant midstream urine samples that met this threshold at baseline. It also notes that bacterial culture data were unavailable for some participants because some samples had low volume.

These measures represent different features of culture findings. Counts describe the quantity of cultured bacteria; presence or absence indicates whether a species was detected; and the threshold classification identifies samples meeting the stated diagnostic criterion. Such measures can characterize changes in detected urinary bacteria over follow-up. However, the registry record does not report numerical endpoint findings, so the size or direction of any changes cannot be established from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the design allow?

The study is described as non-randomized and parallel. In a parallel design, participants belong to a group whose observations can be compared with those of other groups. Here, the clinician determined whether patients with RUTI received prophylaxis or were managed under clinical observation. Because assignment was not random, differences between groups may reflect the reasons for treatment selection, participant characteristics, or other factors, as well as any treatment-related differences. This is a general feature of non-randomized comparisons, not a claim about what happened to these participants.

The healthy population is a distinct study group, but it is not equivalent to a randomized control group for patients with recurrent infections. Its role and any planned comparisons are not described in detail in the registry record. The record also does not report whether statistical adjustment was planned or performed. Without reported methods and results, readers cannot determine how the investigators handled potential confounding.

What do the microbiota measures capture?

The primary outcome description specifies culture-based measurements of bacterial counts, whether named species were present or absent, and whether a sample met the stated diagnostic threshold of 10^5 CFU/mL of one species. Counts are quantitative measures, while presence or absence and threshold status are categorical descriptions. These outcomes answer related but different questions. A change in count need not imply a change in presence, and a threshold classification does not convey the full range of bacterial counts.

The registry describes measurements at baseline and 3-, 6-, 9-, and 12-months. Repeated observations from the same participant are statistically related rather than independent. In general, an analysis of repeated measurements should account for that dependence; treating each observation as unrelated can make uncertainty estimates misleading. The statistical approach to repeated measurements is not reported in the registry record. Nor does the record state how changes from baseline, comparisons between groups, or multiple bacterial species and outcome definitions were modeled.

How should precision be assessed?

In general, a confidence interval expresses a range of values compatible with the data and an analysis model, and its width conveys precision. A narrow interval indicates greater precision than a wide interval, while an interval that includes values representing little or no difference may leave substantial uncertainty about the effect. Confidence intervals for the primary outcome are not reported in the registry record, and no numerical effect estimate is reported. Accordingly, the precision of any microbiota comparison cannot be assessed from the registry information.

In general, a p-value describes how unusual the observed data would be under a specified statistical model and null hypothesis. It does not measure the size or clinical importance of an effect, and it does not correct for bias from non-random assignment or missing measurements. The registry record reports no analysis results or p-values. The statistical tests, model specifications, and any covariate adjustments are not reported in the registry record.

What does over-dispersion mean?

In general, count data can vary more than a simple statistical model expects; this is called over-dispersion. If it is present and not accommodated, uncertainty may be understated. Bacterial counts are part of the endpoint description, but the registry record does not report whether over-dispersion was assessed or which count-data model, if any, was used. This is a general methodological consideration, not evidence that over-dispersion occurred in this study.

How should planning illustrations be read?

The stated assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations are expressed as participants per arm for 80% power or other stated power levels; time-to-event calculations are described in terms of total events. These are planning scenarios, not observed power and not evidence that the study had a particular probability of detecting an effect. The registry record does not report the numerical observed-effect estimate or numerical planning results, so the illustrations cannot be evaluated quantitatively from the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Antibiotic Prophylaxis", "Healthy Population", "Clinical Observation")
n      <- c(17, 19, 10)
events <- c(3, 2, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Antibiotic Prophylaxis  17  3  17.6  3.8  43.4  6.2  41.0  6.4  41.4
ARM  Healthy Population  19  2  10.5  1.3  33.1  2.9  31.4  3.2  31.7
ARM  Clinical Observation  10  1  10.0  0.3  44.5  1.8  40.4  2.3  41.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome of changes to the urinary microbiota and secondary outcomes concerning urine metabolic profiles, antibiotic susceptibility, and pro-inflammatory cytokines. The microbiota endpoint itself includes several bacterial groups, outcome forms, and follow-up times. Testing multiple outcomes or comparisons can increase the chance of finding an apparently notable result by chance. In general, a statistical plan may define a primary comparison, control multiplicity, or treat secondary findings as exploratory. The registry record does not report a multiplicity strategy or identify which comparisons were prespecified for analysis.

The record notes that bacterial culture data were not available for all participants because some samples had low volume. It does not report the number of unavailable samples, which groups or visits they came from, or whether missingness was related to participant characteristics or culture findings. In general, missing measurements can affect estimates when the likelihood of a measurement being unavailable is related to the outcome or other relevant factors. The approach to missing data is not reported in the registry record.

The record does not describe analysis populations, such as whether analyses included all enrolled participants, only participants with available cultures, or another defined set. It also does not report participant flow by group or follow-up visit. Without those details, it is not possible to establish which participants contributed to each endpoint analysis or how closely the analyzed samples represent the enrolled groups. Analysis methods and numerical outcome results are not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The posted safety figures list zero serious adverse events, zero other adverse events, and zero deaths in each of the named groups. The serious-event risk populations are reported as 25 for Antibiotic Prophylaxis, 19 for Healthy Population, and 12 for Clinical Observation. The other-event risk populations are reported as 25, 19, and 12, respectively. These are the recorded populations at risk for the listed safety categories; they should not be replaced by total enrollment when reading these figures.

A zero count means that no event of that category was recorded in the stated risk population in the registry results. It is not the same as proving that an event cannot occur or that treatment has no safety risks. Event counts alone also do not describe how safety events were collected, how long each participant was observed for safety, or whether events were attributed to treatment. Those details are not reported in the registry record.

Because the study is non-randomized, the safety counts do not support a like-for-like causal comparison between prophylaxis and clinical observation. The registry record reports no serious adverse-event terms. These figures should be read as descriptive reporting, not as a complete estimate of comparative safety.

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

The registry record identifies a study of antibiotic prophylaxis in children with RUTI, with a focus on urinary microbiota and additional measures of urine metabolism, antibiotic susceptibility, and pro-inflammatory cytokines. It records a completed Phase 4, non-randomized, parallel study with total enrollment of 59. The treatment decision was made by clinicians, and the record describes follow-up culture measurements at baseline and 3-, 6-, 9-, and 12-months.

What the record does not establish is the observed magnitude or direction of changes in urinary microbiota. Numerical primary-outcome findings, effect estimates, and uncertainty measures are not reported in the registry record. The outcome definition explains what investigators intended to measure, but it cannot stand in for observed results. The registry also does not report numerical findings for the listed secondary outcomes.

The non-randomized allocation is important: comparisons between groups may be influenced by differences in the patients selected for prophylaxis and those managed by clinical observation. The healthy population is not a randomized control for the RUTI groups. The record does not report adjustment methods that would allow readers to assess how potential confounding was addressed. Missing culture data due to low sample volume add uncertainty about the analyzed measurements, and the extent and handling of that missingness are not reported.

The safety figures record zero serious adverse events, zero other adverse events, and zero deaths for the listed groups. These descriptive counts do not establish the absence of risk or prove a comparative safety difference. In short, the registry record documents the study’s research question, design, outcome definitions, and recorded safety counts, but it does not provide the outcome evidence needed to quantify microbiota changes or infer a causal effect of prophylaxis.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its primary outcome connects clinical microbiology with repeated measurement over time. The registry describes bacterial counts, presence or absence, and a threshold classification, across multiple named organisms and follow-up visits. Each measure captures a different feature of urine culture results, so interpretation depends on clearly defining the outcome and the comparison being made.

The design also illustrates why allocation matters. Clinicians determined whether patients with RUTI received prophylaxis, making the comparison non-randomized. In general, when treatment selection is related to participant or clinical characteristics, observed group differences may combine treatment effects with pre-existing differences. Statistical adjustment can sometimes address measured factors, but the registry record does not report whether adjustment was used, and adjustment cannot guarantee removal of all confounding.

Repeated measurements and incomplete culture availability are further statistical considerations. Measurements from the same participant are related, and missing samples can affect interpretation if availability is associated with the outcome. The record acknowledges low-volume samples but does not describe the extent, pattern, or analysis of missing cultures. These issues make the analysis methods and participant flow important for understanding any eventual findings.

The registry record does not report numerical primary or secondary outcome results. That absence is consequential: without estimates and measures of uncertainty, readers cannot judge the magnitude, direction, or precision of microbiota changes. The study’s question and outcome structure are informative, but they are not substitutes for reported analytical results.

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 registry record leaves several trial-specific limitations unresolved. It does not report detailed participant characteristics or group-specific enrollment totals, so the similarity of the clinical groups cannot be assessed from the record. Because prophylaxis was determined by a clinician, treatment selection may be associated with clinical differences that also relate to outcomes. The record does not describe statistical adjustment for those differences.

The primary outcome includes several culture-based measures for multiple bacterial groups and observations at baseline and 3-, 6-, 9-, and 12-months. The statistical plan for combining or comparing those measures is not reported in the registry record. It is also not clear which specific comparisons were designated as primary analytical contrasts or whether multiplicity was addressed.

The record explicitly notes that some bacterial culture data were unavailable because of low sample volume. It does not quantify this missingness, describe its distribution by group or visit, or report how unavailable measurements were handled. Consequently, the relationship between total enrollment and the number of observations contributing to any outcome analysis cannot be assessed.

Finally, numerical primary and secondary outcome results, uncertainty estimates, and analysis methods are not reported in the registry record. The record’s completed status does not resolve those reporting gaps. The safety figures are limited to recorded counts and risk populations; details of safety ascertainment and exposure time are not reported. These limitations constrain both quantitative interpretation and causal conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Antibiotic Prophylaxis on Recurrent UTI in Children — NCT02357758.
• Registry record last updated 2021-09-21; status last verified 2015-09.
• Results first posted 2019-10-14.
• 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

NCT02357758 is a completed Phase 4, non-randomized, parallel study titled Effects of Antibiotic Prophylaxis on Recurrent UTI in Children. Total enrollment is 59. The registry record gives a start date of 2012-09 and a primary completion date of 2016-01. It describes a clinician-selected antibiotic prophylaxis group for patients with RUTI, a clinical observation group for patients with RUTI, and a healthy population.

The primary outcome concerns changes in urinary microbiota assessed by urine culture at baseline and 3-, 6-, 9-, and 12-months. Listed secondary outcomes concern urine metabolic profiles, antibiotic susceptibility, and pro-inflammatory cytokines. The record notes unavailable culture data due to low sample volume. It reports zero serious adverse events, zero other adverse events, and zero deaths in the listed groups.

Numerical outcome findings, analysis methods, missing-data handling, and multiplicity methods are not reported in the registry record. The non-randomized design means group comparisons are not like-for-like randomized comparisons.