Treatment of Giardia Lamblia Infections in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Giardia Lamblia Infections in Children (NCT02942485), a randomized phase 4 study. The primary outcome is Clinical Recovery.

2. Clinical Question

3. Trial Design

The registry describes a randomized, open-label, parallel trial, listed as phase 4. It was sponsored by Helsinki University Central Hospital and studied treatment of Giardia lamblia infections in children. The record gives enrollment as 8 and the status as terminated. The study start date is 2016-12-01, and the primary completion date is 2019-12-31. The reason for termination is not reported in the registry record.

The treatment groups differed in both drug and route. Rectal metronidazole was given once daily for 3 days, with dose based on weight and with suppositories not halved. Oral tinidazole was described as a single dose of 50 mg/kg, maximum 2 g/dose. The registry does not report whether treatment adherence was assessed or how deviations from the assigned regimen were handled.

Randomization is intended to reduce systematic differences between assigned groups, but the registry does not describe the sequence-generation method, allocation concealment, or any stratification. Because masking was listed as none, participants and caregivers, and potentially those assessing outcomes, could know which treatment was received. The record says parents or caregivers were interviewed using a structured questionnaire for the primary outcome, but does not say whether outcome assessors were independent or unaware of assignment.

The number enrolled and the arm-specific entries in the outcome and safety records do not line up in a way that the registry explains. The primary-outcome entries list Metronidazole with n=4.0 and value 4.0, and Tinidazole with n=0.0 and value 0.0. The safety record instead lists 7 at risk in the Metronidazole group and 1 at risk in the Tinidazole group. These fields may describe different analysis populations or data structures, but their relationship is not reported in the registry record. The planned analysis, analysis populations, and reasons for termination are also not 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 3 participants in the "Metronidazole" and 1 participant "Tinidazole" Arm/Group were asymptomatic and the main primary outcome (clinical cure) could not be assessed

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 Clinical Recovery, measured over 10 days.

The primary endpoint was clinical recovery, recorded as a count of participants. The registry defines recovery as resolution of symptoms by day 10 post-treatment, assessed by interviewing parents or caregivers with a structured questionnaire. This endpoint focuses on whether symptoms have resolved within the stated assessment period. Such a patient-centered outcome can describe a clinical state that matters to families, rather than relying only on a laboratory result.

Interpretation is constrained by the record’s note that 3 participants in the Metronidazole arm and 1 participant in the Tinidazole arm were asymptomatic, and that the main primary outcome could not be assessed for them. Being asymptomatic at the point of assessment is not the same as a documented outcome under the stated recovery definition, according to the registry’s own note. The record does not explain how asymptomatic status relates to baseline symptoms, eligibility, or the arm-level values.

The posted primary-outcome entries give Metronidazole n=4.0 and value 4.0, and Tinidazole n=0.0 and value 0.0. Given the assessment note, those entries should not be treated as a clear, comparable estimate of clinical recovery without further explanation. The timing, questionnaire scoring rules, and handling of participants whose symptoms could not be assessed are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can clarify what a trial result can establish, but the registry record does not report the planned or completed analysis for the primary outcome. It lists 0 analyses. Accordingly, the methods explain general statistical principles and the assumptions stated for the planning illustration; they should not be mistaken for methods confirmed as used to analyze this trial.

What does a count endpoint represent?

The primary endpoint is a count of participants meeting the clinical recovery definition. For a binary outcome, each participant is classified according to whether the outcome occurred or did not occur, provided the outcome can be assessed. A group count alone does not describe the probability of recovery unless the relevant denominator and the population included in the count are clear. Here, the registry lists n=4.0 and value 4.0 for Metronidazole, and n=0.0 and value 0.0 for Tinidazole. The registry’s note about asymptomatic participants makes the meaning of these entries difficult to establish. It does not explain whether the entries refer to all assigned participants, only assessed participants, or another population.

Why does randomization matter?

In general, random assignment aims to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average across repeated trials. It does not guarantee balance in a particular trial, especially when the amount of information is limited. The registry identifies the study as randomized but does not report how the random sequence was created, whether assignment was concealed, or whether the intended allocation was maintained. Those details matter when judging how well randomization protected the comparison from selection effects.

What does open-label mean for outcome assessment?

Open-label means that masking was listed as none. Knowledge of treatment assignment can affect expectations, reporting, and assessment, particularly for an outcome based on symptoms reported in an interview. A structured questionnaire can make assessments more consistent, but it does not by itself remove the possibility that knowledge of treatment influences answers or interpretation. The registry does not report whether the interviewer was independent, whether the questionnaire was validated, or how responses were classified.

How should uncertainty be represented?

In general, a confidence interval expresses the range of treatment effects compatible with the observed data under the assumptions of the analysis. Its width reflects statistical precision; a wide interval indicates that the data allow a broad range of possible effects. A test result or point estimate without an uncertainty interval can be hard to interpret, because it does not show how much the estimate might vary. The registry record does not report a confidence interval or a formal statistical test for the primary endpoint. No conclusion about the precision of a treatment contrast can therefore be drawn from the posted primary values.

What would a non-inferiority analysis require?

In general, a non-inferiority analysis asks whether the results rule out a disadvantage larger than a prespecified margin. The margin must be defined in advance and interpreted in relation to the clinical question. The analysis should also state how outcomes that are missing or cannot be assessed are handled, because exclusions or different analysis populations can affect a non-inferiority conclusion. The record states a non-inferiority hypothesis and a cure target of at least 72%, but does not report a non-inferiority margin, analysis population, statistical test, or analysis plan. The stated hypothesis therefore cannot be evaluated as a completed non-inferiority analysis from the registry record.

What do the planning assumptions mean?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations are conditional illustrations: they indicate how a future study’s required sample size would depend on assumptions about the effect and analysis. They are not observed power, and they do not demonstrate that the completed trial was adequately powered. The registry does not report the trial’s own sample-size justification or design assumptions.

For binary outcomes, over-dispersion is generally less central than it is for some count models, but variation in event rates and uncertainty from limited observations still affect precision. More generally, a statistical model should reflect the outcome type, the allocation, the analysis population, and the study’s data. The model used for the posted results is not reported in the registry record. Neither the planning illustration nor general statistical principles can fill in that missing analysis information.

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("Metronidazole")
n      <- c(4)
events <- c(4)
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  Metronidazole  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of clinical recovery and identifies two secondary outcome categories: participants with side effects and participants with a negative Giardia lamblia antigen test. When a study evaluates multiple outcomes or performs multiple comparisons, the chance of obtaining an apparently notable result by chance can increase. Statistical approaches to multiplicity can control or describe that risk, but the suitable approach depends on the prespecified questions and analysis plan.

No multiplicity strategy is reported in the registry record. The record also lists 0 analyses, so it is not possible to determine whether any adjustment was performed or whether the outcomes were analyzed according to a prespecified hierarchy. The result entries for the primary outcome do not include an inferential analysis, and the secondary outcome categories do not have posted analysis results in the registry record described by the record.

Missingness and outcome assessability are central concerns for the primary endpoint. The registry says that 3 participants in the Metronidazole arm and 1 participant in the Tinidazole arm were asymptomatic, so clinical cure could not be assessed. It does not report how these participants were handled analytically, whether any other outcomes were missing, or whether follow-up was complete. It also does not explain the relationship between the primary-outcome arm entries and the safety denominators.

The analysis populations are not reported in the registry record. In general, intention-to-treat and per-protocol populations answer related but not identical questions, and exclusions after randomization can affect treatment comparisons. Without a stated analysis population and rules for handling unassessed outcomes, the reported entries cannot be interpreted as a complete, comparable analysis of all randomized participants. The reason for termination and any effect on the planned analyses are also not reported.

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.

Most frequent non-serious adverse event terms

The safety record lists serious adverse events as 0 in the Metronidazole group, with 7 at risk, and 0 in the Tinidazole group, with 1 at risk. Deaths are recorded as 0 in each group. These are counts as posted in the registry; they should not be interpreted as proof that serious adverse events cannot occur or that the treatments have equivalent safety.

For other adverse events, the record lists 1 affected participant among 7 at risk in the Metronidazole group and 0 among 1 at risk in the Tinidazole group. The record does not provide further details about the non-serious event in the registry record described. It also does not explain why the at-risk numbers differ from the primary-outcome entries, or whether safety follow-up and primary-outcome assessment used different populations.

In general, a zero count in a small or limited safety record leaves substantial uncertainty about the underlying risk. A meaningful comparison depends on clear denominators, definitions, follow-up, and a statistical assessment of uncertainty. The registry record does not report a safety analysis or confidence intervals. These figures describe the events recorded for the stated at-risk groups, not a definitive comparison of safety.

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

The registry record documents a randomized, open-label study comparing rectal metronidazole with oral tinidazole for pediatric giardiasis. It gives treatment regimens, defines clinical recovery as symptom resolution by day 10 post-treatment, and states the investigators’ non-inferiority hypothesis. It also reports an enrollment of 8 and a terminated status. These details establish the intended research question and some features of the record.

They do not establish that the primary comparison was successfully completed or that one regimen was superior, equivalent, or non-inferior. The primary outcome note says that asymptomatic participants could not be assessed for clinical cure. The posted arm entries are not explained in relation to that note, and the record reports no formal analysis, effect estimate, confidence interval, or hypothesis test. The stated hypothesis and cure target of at least 72% should therefore be read as the study’s aim, not as an observed conclusion.

The safety entries likewise require caution. The registry records 0 serious adverse events in each group, with different at-risk counts, and records other adverse events for the listed groups. Those counts do not by themselves establish the comparative safety of the regimens. The record does not report the safety analysis, the reason for the different denominators, or a measure of statistical uncertainty.

More generally, a trial result is informative only when the outcome definition, assessment, analysis population, denominators, and statistical uncertainty can be understood together. Several of these details are not reported in the registry record. The appropriate interpretation is therefore descriptive and limited to the posted entries. Further details about the study conduct and analysis would be needed to interpret the apparent outcome values as evidence about treatment effects.

14. Why This Trial Matters Statistically

This trial is statistically important as an example of how outcome assessability and denominator clarity shape interpretation. The stated clinical endpoint depends on symptoms resolving by a specified assessment time. Yet the registry says that some participants were asymptomatic and that clinical cure could not be assessed for them. That distinction matters: an outcome that cannot be assessed should not automatically be treated as either a recovery or a failure unless the protocol and analysis define it that way.

The record also illustrates why reported counts need context. The primary-outcome entries list n=4.0 and value 4.0 for Metronidazole, and n=0.0 and value 0.0 for Tinidazole, while the safety record gives at-risk counts of 7 and 1. The registry does not explain how these entries connect to enrollment, randomization, or the asymptomatic participants. Without those links, readers cannot tell which participants contributed to each result or whether the groups were analyzed comparably.

Randomization, a structured questionnaire, and a clearly defined endpoint can support a rigorous comparison, but they do not replace transparent reporting of the analysis. This record does not report the analysis plan, missing-data approach, non-inferiority margin, or inferential results. For a non-inferiority question in particular, an explicit margin and uncertainty around the treatment contrast are essential to distinguish evidence of non-inferiority from an inconclusive comparison.

The statistical lesson is not a conclusion about either drug. It is that interpretable trial evidence depends on coherence between the question, the outcome definition, the denominators, and the analysis. The record’s limitations prevent a clear estimate of the comparative clinical outcome.

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 has limitations specific to this study. It reports that the primary outcome could not be assessed for 3 participants in the Metronidazole arm and 1 participant in the Tinidazole arm because they were asymptomatic. It does not clarify whether they had symptoms before treatment, how they were classified for analysis, or whether the outcome definition was modified for them. This leaves uncertainty about what the arm-level outcome entries represent.

The arm entries for the primary outcome and the at-risk counts in the safety record differ, and the record does not reconcile them. Although enrollment is listed as 8, the relationship between enrollment, treatment assignment, outcome assessment, and safety follow-up is not reported. The number randomized by arm, the number completing follow-up, and reasons for any exclusions or unavailable measurements are not reported in the registry record.

The study was open-label, and the primary endpoint was based on a caregiver interview. The record does not report whether outcome assessment was blinded, how the questionnaire was scored, or whether the same assessment procedures were applied across groups. The randomization method and allocation concealment are also not reported.

The registry status is terminated, but the reason for termination and its impact on recruitment, follow-up, or analysis are not reported. A statistical analysis plan, sample-size justification for the trial, non-inferiority margin, analysis populations, missing-data procedures, and formal results are not reported. The registry does not provide enough information to determine whether the posted counts represent the planned analysis or to assess the precision of the comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment of Giardia Lamblia Infections in Children — NCT02942485.
• Registry record last updated 2020-11-18; status last verified 2020-11.
• Results first posted 2020-11-18.
• 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

The record concerns a phase 4 randomized, open-label, parallel trial sponsored by Helsinki University Central Hospital. It compares rectal metronidazole, given once daily for 3 days with dose based on weight, with a single oral dose of tinidazole. Enrollment is listed as 8; the status is terminated. The study start date is 2016-12-01 and primary completion date is 2019-12-31.

The primary outcome is clinical recovery, defined as symptom resolution by day 10 post-treatment and assessed by caregiver interview. The registry notes that 3 Metronidazole participants and 1 Tinidazole participant were asymptomatic, making the primary outcome unassessable for them. The posted outcome entries do not resolve how this issue was handled, and no formal analysis is reported. The record also lists secondary outcomes for side effects and negative Giardia lamblia antigen tests. Serious adverse events and deaths are recorded as 0 in both groups, but at-risk counts differ. The analysis plan, reasons for termination, and explanation of the differing outcome and safety entries are not reported in the registry record.