A Study of Kytril (Granisetron) in the Prevention of Post-Operative Nausea and Vomiting (PONV) in Pediatric Subjects Undergoing Tonsillectomy or Adenotonsillectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Kytril (Granisetron) in the Prevention of Post-Operative Nausea and Vomiting (PONV) in Pediatric Subjects Undergoing Tonsillectomy or Adenotonsillectomy (NCT00231478), a non-randomized phase 4 study. The primary outcome is Number of Patients With no Vomiting.

2. Clinical Question

The study concerns postoperative nausea and vomiting in children after a specified type of surgery. Its brief summary says that it evaluates the efficacy and safety of a single injection of granisetron, while the recorded primary endpoint addresses vomiting rather than nausea. The named secondary outcomes include time to first vomiting episode and adverse experiences, in addition to the number of patients with no vomiting. The record does not provide results for these outcomes.

There is an important design ambiguity when interpreting the comparison. The title and brief summary describe randomization and the official title describes a double-blind study, but the allocation field says non-randomized and the masking field says none. The registry also flags the arms as not a like-for-like control comparison. The record therefore does not support assuming that assignment to the two doses was randomized or blinded.

3. Trial Design

This is a completed Phase 4 study with a parallel model and a recorded enrollment of 171. The brief summary says the planned sample size was 170. The study dates in the record are 2007-04 for start and 2007-12 for primary completion. The condition is postoperative nausea and vomiting, and the population is pediatric patients undergoing tonsillectomy or adenotonsillectomy under general anesthesia.

The two intervention entries are granisetron. The arm labels identify Granisetron 20 ug/kg and Granisetron 40 ug/kg. The brief summary describes a single intravenous dose of either 20 micrograms or 40 micrograms, administered 15 minutes before the end of surgery. Arm descriptions are blank, so additional details about how the groups were managed are not reported in the registry record.

The design fields do not align with the narrative descriptions. The allocation field records NON RANDOMIZED, and the masking field records NONE. In contrast, the title and brief summary use randomized language, and the official title calls the study double-blind. These conflicting descriptions cannot be resolved from the registry record. The record's own note cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Any contrast between the dose groups should therefore be read with that limitation in mind.

The primary outcome is the number of evaluable patients with no vomiting from the end of surgery through 2 hours after surgery. The named secondary outcomes are number of patients with no vomiting, time to first vomiting episode, and adverse experiences; the primary outcome is also recorded separately. Four outcome measures are listed, but the full details of every measure are not reported in the registry record. The record lists no analyses. It does not report a statistical analysis plan, an account of allocation procedures, or the criteria used to define the evaluable population.

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: Evaluable Patients

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 Number of Patients With no Vomiting, measured over 0-2h after end of surgery (time of extubation).

The primary endpoint counts evaluable patients with no vomiting up to 2 hours after surgery. Its recorded timeframe is 0-2h after end of surgery (time of extubation), and the outcome description defines success as no emesis during that interval. It is a binary participant-level measure: each evaluable patient either meets the no-vomiting definition or does not.

This endpoint focuses on whether vomiting occurred during an early postoperative period. As a general statistical point, a binary endpoint can be summarized by the number of participants meeting the definition and the number assessed, or by a proportion when the denominator is known. The registry record does not report either the primary outcome counts or the denominator for the evaluable population, so no observed proportion can be interpreted from the record.

The endpoint measures vomiting, not the full experience of postoperative nausea and vomiting. Although the condition and study title refer to both nausea and vomiting, the primary outcome definition specifically refers to emesis. The registry record does not report a primary endpoint measure of nausea. It also does not report whether additional assessments or rules were used to classify vomiting episodes beyond the stated no-emesis definition.

A short, specified observation window makes the outcome interpretable as an early postoperative measure, but it does not describe events outside that window. The named secondary outcome of time to first vomiting episode addresses timing in a different way; results for that outcome are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome measure?

The endpoint is recorded as a number of participants, with the parameter described as a count. It concerns evaluable patients with no vomiting during the interval from the end of surgery through 2 hours after surgery. The stated definition is no emesis up to 2 hours after surgery. These details identify a binary outcome for each participant, even though the registry expresses the result as a number of patients.

General statistical explanation: for a binary outcome, the count is meaningful alongside the number of participants assessed. A proportion can describe how common the outcome was within an arm, while a comparison between arms can describe the difference or another contrast between those proportions. Those summaries require outcome counts and denominators. Neither the primary counts nor the evaluable denominators are reported in the registry record.

What can be concluded from the analysis record?

The registry lists no analyses. No statistical model, test, adjustment method, confidence interval, or p-value for the primary endpoint is reported in the registry record. The record also does not state whether the primary analysis was intended to use a particular method for missing observations or to account for other variables. It would not be appropriate to infer an analysis plan from the endpoint type or from the narrative description of the study.

General statistical explanation: an analysis method should match the outcome and the design, and its assumptions should be made explicit. For a count of participants meeting a binary definition, a method might summarize event frequencies or compare them across groups. The choice of method affects the estimate and its uncertainty, particularly when the outcome denominator is limited or differs between groups. No method can be attributed to this study from the registry record.

Why does the design description matter?

The allocation field says NON RANDOMIZED, while the study title and brief summary describe randomization. The official title also says double-blind, but the masking field says NONE. These are conflicting record descriptions, and the registry note specifically warns that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The available information does not clarify how participants entered each arm or whether the narrative or the design fields reflect the implemented study.

General statistical explanation: random allocation is intended to balance measured and unmeasured participant characteristics across groups on average. Without randomization, group differences may reflect factors other than the intervention. Masking can also affect how outcomes are assessed or reported, depending on the outcome and study procedures. Because assignment and masking are unresolved in this record, the two dose groups should not be interpreted as though those protections were established.

How should the planning illustration be read?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. Its effect to detect is specified as a fraction of the observed effect. For non-time-to-event outcomes, its sample sizes are expressed as participants per arm; time-to-event calculations use a total number of events. These are planning assumptions for an illustration based on an observed effect, not reported design assumptions from the trial itself.

The registry record does not report the observed primary effect needed to interpret such an illustration numerically. Any planning calculation based on an observed effect depends on that effect and on the stated assumptions. General statistical explanation: a planning sample size is a design quantity, not an observed result. It does not establish that the trial had a particular probability of detecting an effect after the data were collected. The illustration should not be described as observed power.

General statistical explanation: a confidence interval, when reported, describes a range of values compatible with the data and the method's assumptions. Its width communicates precision; an estimate without an interval gives less information about uncertainty. No confidence interval for the primary outcome is reported in the registry record, so precision cannot be judged.

What does the record say about other outcomes?

The record names time to first vomiting episode and adverse experiences as secondary outcomes, alongside the number of patients with no vomiting. A time-to-event outcome concerns when an event occurs, rather than only whether it occurs within a fixed window. General statistical explanation: time-to-event methods can account for participants whose event time is not observed during follow-up, but they require suitable event and follow-up information. The record does not report a time-to-event analysis or its results.

General statistical explanation: when a study examines multiple outcomes, the chance of finding at least one apparently notable result can depend on how many analyses are conducted and how they are handled. A multiplicity strategy may specify which outcome is primary and whether or how other tests are adjusted or interpreted. The registry record does not report a multiplicity plan or analyses, so no adjustment or testing hierarchy should be assumed.

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("Granisetron 20 ug/kg", "Granisetron 40 ug/kg")
n      <- c(70, 73)
events <- c(61, 69)
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  Granisetron 20 ug/kg  70  61  87.1  77.0  93.9  77.3  93.1  77.3  93.0
ARM  Granisetron 40 ug/kg  73  69  94.5  86.6  98.5  86.7  97.8  86.7  97.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies number of patients with no vomiting as the primary outcome and names time to first vomiting episode and adverse experiences among the secondary outcomes. It also lists four outcome measures. The record does not provide full details for every listed measure, and it lists no analyses. A strategy for controlling or interpreting multiplicity across outcomes is not reported in the registry record.

General statistical explanation: evaluating several outcomes can make isolated findings harder to interpret, particularly if the analyses or priorities were not specified in advance. A prespecified hierarchy or adjustment can help clarify which comparisons are confirmatory and how other findings should be treated. The registry record does not say whether such a strategy was used. No inferential results are reported, so multiplicity cannot be evaluated from the posted results.

The primary population is described as evaluable patients. The registry does not define evaluability, report how many participants qualified, or give the number with observed primary endpoint data. The difference between the recorded enrollment of 171 and the number analyzed cannot be assessed because the latter is not reported. A missing-data method, including any assumptions about participants without outcome assessments, is not reported in the registry record.

General statistical explanation: missing outcome data can affect an estimate when the likelihood of missingness is related to participant characteristics or outcomes. The analysis population and rules for handling missing observations therefore matter when interpreting a result. With no reported primary counts, denominator, analysis population detail, or missing-data method, the record does not permit assessment of these issues.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (2.5%), post procedural haemorrhage (2.5%), oral intake reduced (1.3%), oxygen saturation reduced (1.3%), procedural pain (1.3%).

The registry reports serious adverse experiences among 6 of 79 participants at risk in the Granisetron 20 ug/kg arm and 2 of 78 at risk in the Granisetron 40 ug/kg arm. For other adverse experiences, it reports 6 of 79 at risk and 4 of 78 at risk, respectively. These are participant counts as recorded for the two safety categories; they are not results for the primary no-vomiting endpoint.

The registry also lists serious-event terms with percentages: dehydration, 2.5%; post procedural haemorrhage, 2.5%; oral intake reduced, 1.3%; oxygen saturation reduced, 1.3%; procedural pain, 1.3%; and migraine, 1.3%. The record does not provide counts alongside these term percentages or explain whether participants could contribute to more than one listed term. The figures should therefore be read as registry-reported safety descriptions, not combined into a total.

Deaths are not reported in the registry record. These safety entries do not establish a comparative safety conclusion: the design fields identify a non-randomized comparison, and the record does not report inferential analyses for adverse experiences.

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

The record establishes that the study addressed two granisetron dose levels in pediatric patients undergoing tonsillectomy or adenotonsillectomy under general anesthesia. It defines a primary outcome based on whether evaluable patients had no vomiting during the early postoperative interval through 2 hours after surgery. It also reports safety counts for serious and other adverse experiences in the two dose arms.

What the record does not establish is the primary outcome result. Counts of patients with no vomiting, the evaluable denominators, and a comparison between doses are not reported. There is no reported estimate of the difference, uncertainty interval, or p-value. The absence of these results should not be interpreted as showing equal outcomes or no difference; it means that the registry record does not provide the outcome information needed to make that assessment.

The dose comparison is also limited by inconsistent design information. The title and brief summary describe randomization, and the official title describes double blinding, but the allocation and masking fields say non-randomized and none. The record cautions that the arms are not a like-for-like control comparison. It is therefore not appropriate to treat any between-arm contrast as an unambiguous randomized estimate.

General statistical explanation: a study result is most informative when the outcome estimate is accompanied by its uncertainty and when the design supports the intended comparison. A count without a denominator does not give the outcome frequency, and an estimate without uncertainty gives limited information about precision. In this record, those elements are missing for the primary outcome.

The safety entries provide some descriptive information but do not answer the primary efficacy question. Nor do the listed adverse-event counts, by themselves, show that one dose is safer than the other. The record supplies no analysis of those outcomes and flags the comparison design as non-randomized. The findings that can be stated are therefore limited to the study description and the recorded safety counts, not a conclusion about treatment effect or comparative safety.

14. Why This Trial Matters Statistically

This record illustrates why design fields and narrative descriptions both matter in clinical-trial interpretation. The title and brief summary describe randomized treatment, and the official title describes double blinding. Yet the structured allocation and masking fields say non-randomized and none, and the registry note warns that the groups are not a like-for-like control comparison. Readers need to recognize that these statements do not agree rather than silently choosing the description that implies a stronger comparison.

It also shows why an endpoint definition is not the same as an endpoint result. The registry specifies a clinically focused, time-bounded measure: evaluable patients with no vomiting up to 2 hours after surgery. But without outcome counts and denominators, the frequency of that result and the contrast between dose groups cannot be estimated from the record. Clear definitions support interpretation, while reporting the observed data is necessary to answer the study question.

The distinction between enrollment and analysis population is another statistical issue. Enrollment is 171, while the primary population is described as evaluable patients. The number of evaluable patients and the criteria defining that group are not reported. Without them, readers cannot tell how much of the enrolled group contributed primary outcome data or assess whether exclusions could affect interpretation.

Finally, the record lists safety counts but no analyses and no primary outcome results. This emphasizes that a completed study status does not itself communicate what the data showed or how precisely an effect was estimated. Statistical interpretation depends on transparent reporting of design, analysis populations, outcome data, and uncertainty. Several of those elements are absent or inconsistent in this record.

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 most direct limitation is that the registry record does not report results for the primary endpoint. It provides no counts of evaluable patients with no vomiting, no primary outcome denominators, and no effect estimate or uncertainty interval. The primary clinical question therefore remains unanswered by the posted results.

The design description is internally inconsistent. The title and brief summary describe a randomized study, and the official title describes double blinding, whereas the allocation field records NON RANDOMIZED and the masking field records NONE. The registry note further cautions that the arms are not a like-for-like control comparison. The record does not explain how participants were assigned or resolve the conflicting descriptions.

The primary outcome population is evaluable patients, but the record does not define evaluability or report how many participants were included in that population. Although enrollment and the planned sample size are reported, neither identifies the primary analysis denominator. A missing-data approach and a statistical analysis plan are not reported in the registry record.

Four outcome measures are listed, but the record names only three secondary outcomes and does not report analyses. It does not describe a multiplicity strategy, outcome estimates for the named secondary endpoints, or adjustment for potential differences between groups. The arm descriptions are blank. These omissions limit understanding of what was measured and how the results were intended to be interpreted.

The safety entries are descriptive and do not include reported deaths; death information is not reported in the registry record. The listed serious-event terms are accompanied by percentages but not counts, and the record does not explain whether terms can overlap. These limitations, together with the non-randomized allocation field, restrict comparative interpretation of both efficacy and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Kytril (Granisetron) in the Prevention of Post-Operative Nausea and Vomiting (PONV) in Pediatric Subjects Undergoing Tonsillectomy or Adenotonsillectomy — NCT00231478.
• Registry record last updated 2018-03-27; status last verified 2018-02.
• Results first posted 2011-04-28.
• 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 registry record describes a completed Phase 4, parallel study of granisetron in pediatric patients undergoing tonsillectomy or adenotonsillectomy with general anesthesia. Enrollment is 171, and the brief summary gives a planned sample size of 170. The two arm labels are Granisetron 20 ug/kg and Granisetron 40 ug/kg. The primary outcome is the number of evaluable patients with no vomiting up to 2 hours after surgery.

Descriptions of randomization and masking conflict: the title and brief summary describe randomization, while the allocation field says non-randomized; the official title says double-blind, while the masking field says none. The registry cautions that the arms are not a like-for-like control comparison. Primary outcome results and analyses are not reported in the registry record. Safety counts are reported for serious and other adverse experiences, but they do not resolve the primary question or establish a comparative treatment effect.