This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Dose Escalation Study of Zinc Supplementation in Critically Ill Children (NCT01062009), a non-randomized phase 1, phase 2 study. The primary outcome is Plasma Zinc Concentration Over Time.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01062009 |
| Phase | Phase 1, Phase 2 |
| Condition | Critical Illness |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCSF Benioff Children's Hospital Oakland |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned critically ill children. The registry record lists Critical Illness as the condition and reports enrollment of 24 participants. It does not provide additional population details in the primary-outcome description, so eligibility characteristics and the clinical setting beyond critical illness are not reported in the registry record.
Intervention
The intervention was intravenous zinc sulfate. The low-dose group received 250 mcg/kg/day, divided every 8 hours for 7 days; the medium-dose group received 500 mcg/kg/day q8 hours for 7 days; and the high-dose group received 750 mcg/kg/day q8 hrs for 7 days. The record also includes a control group with no intervention.
Comparator
The listed groups are control, low dose, medium dose, and high dose. Because allocation was non-randomized, the control group is not a like-for-like randomized comparator. Differences between groups could reflect differences in who entered each group as well as differences associated with the assigned regimen.
Primary question
The primary outcome was plasma zinc concentration over time, measured daily during the 7-day study period. The study’s stated purpose was to assess the safety of intravenous zinc in critically ill children and determine an appropriate supplementation dose. The registry record does not report numerical plasma zinc results, so it does not establish from the posted endpoint data how concentrations changed or differed among groups.
3. Trial Design
The registry describes a Phase 1 and Phase 2 study with non-randomized allocation, no masking, and a parallel-group model. Enrollment was 24. The study is marked completed, with a start date of 2008-11 and a primary completion date of 2014-10. UCSF Benioff Children's Hospital Oakland is listed as the sponsor.
Participants were assigned to a no-intervention control group or one of three intravenous zinc sulfate dose groups. The low-dose regimen was 250 mcg/kg/day divided every 8 hours for 7 days. The medium-dose regimen was 500 mcg/kg/day q8 hours for 7 days, and the high-dose regimen was 750 mcg/kg/day q8 hrs for 7 days. The registry’s adverse-event accounting lists 6 participants at risk in each group.
Non-randomized allocation matters when interpreting any apparent differences. Random assignment is a general method for balancing measured and unmeasured participant characteristics across groups, on average. Without randomization, group membership may be related to participant characteristics, clinical decisions, or other factors. The registry record does not report how allocation decisions were made, whether the groups were enrolled concurrently, or whether any adjustment was used to address differences between groups.
No masking was used, according to the record. This describes the reported design but does not specify who knew the group assignments or whether outcome measurement involved safeguards against assessment bias. Those details are not reported in the registry record. The record also does not report a protocol-level account of the intended statistical plan or a sample-size justification. The phase labels and stated study purpose identify a safety and dose-escalation investigation, but they do not substitute for details about the allocation process or analysis plan.
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: One patient was enrolled but withdrawn by PI due to insufficient intravenous access to obtain study labs
Overall Study
| Stage | Control Group | Low Dose Group | Medium Dose Group | High Dose Group |
|---|---|---|---|---|
| STARTED | 7 | 6 | 6 | 6 |
| COMPLETED | 6 | 6 | 6 | 6 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
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.
| Characteristic | Unit | Control Group | Low Dose Group | Medium Dose Group | High Dose Group | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 6 | 6 | 24 | |
| Age, Continuous | years | 1.5 (0.6 to 4.8) | 1.8 (0.8 to 2.8) | 5.3 (1.9 to 6.4) | 2.6 (0.8 to 5.2) | 1.9 (0.65 to 5.6) |
| Sex: Female, Male: Female | Participants | 4 | 3 | 4 | 3 | 14 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 2 | 3 | 10 |
| Pediatric Risk of Mortality (PRISM) III | units on a scale | 12 (5 to 17) | 8 (3 to 16) | 12 (6 to 19) | 9 (7 to 10) | 9 (5 to 17) |
| Pediatric Index of Mortality (PIM) | percentage mortality risk | 3.4 (1.6 to 17.1) | 6.0 (4.2 to 7.2) | 7.0 (4.0 to 23.0) | 5.2 (2.8 to 7.8) | 5.9 (4 to 9.7) |
| Pediatric Logistic Organ Dysfunction (PELOD ) | units on a scale | 11 (4 to 11) | 11 (4 to 19) | 20 (13 to 21) | 21 (14 to 21) | 11 (2 to 21) |
| Number of patients with >= 2 organs failed | participants | 3 | 3 | 4 | 3 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Zinc Concentration Over Time, measured over 7 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mcg/dL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was plasma zinc concentration over time, reported as a continuous measure in mcg/dL. The record specifies the mean as the summary measure and standard deviation as the measure of dispersion. Plasma zinc levels were measured daily during the 7-day study period in each group.
As a general statistical matter, a repeated concentration measure can describe how a biological quantity changes during observation and how its pattern may differ across groups. The mean gives a measure of the group’s central value, while the standard deviation describes the spread of individual observations around that mean. Neither summary alone describes the full distribution or the precision of an estimated group mean.
The endpoint is relevant to the stated purpose of assessing zinc supplementation and dose escalation because it tracks plasma zinc during the study period. However, the registry record does not report the observed mean concentrations, standard deviations, estimates of change, or comparisons between groups. It also does not report a specific primary time point or a statistical model for the repeated measurements. Consequently, the endpoint description identifies what was measured, but the record does not provide enough numerical outcome information to characterize the observed concentration patterns or their uncertainty.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint is named and described, but numerical plasma zinc results are not reported in the registry record. There are no posted group means or standard deviations for the daily measurements in the registry record for this analysis. Therefore, the size, direction, and precision of any change in plasma zinc cannot be described from the registry record. Nor can a between-group difference, dose-response pattern, or uncertainty interval be reported.
The design further limits what a group comparison could establish. Allocation was non-randomized, so the assigned groups should not be treated as though they were created by random assignment. In general, randomization helps reduce systematic differences between groups at the start of a study. When allocation is non-random, baseline differences or allocation decisions may be related to the outcome. The registry record does not report the allocation procedure or baseline characteristics that would help readers assess this concern.
The study lists a control group and three zinc dose groups, but the record’s own design information warns that the arms are not a like-for-like control comparison. Thus, even if numerical outcome differences were available, they would need to be interpreted in light of the non-randomized design. The current record does not provide the outcome estimates needed to make that assessment.
The adverse-event data are more explicit at the group level. The registry lists 6 participants at risk in each group. One participant in the low-dose group is listed as having a serious adverse event; no participants in the control, medium-dose, or high-dose groups are listed as affected by a serious adverse event. No participants are listed as affected by other adverse events in any group. The registry also lists refractory hypoxemia as the top serious adverse-event term at 16.7%. Death counts are not reported in the registry record. These entries describe recorded counts; they do not by themselves establish whether an event was caused by zinc or whether the groups differed in underlying risk.
The record lists 3 outcome measures and 1 analysis, but the specific analysis method is not reported in the registry record. It is therefore not possible to determine whether the analysis accounted for repeated measurements, adjusted for baseline values, or handled missing measurements in a particular way. A single listed analysis count does not establish that all planned analyses are represented or explain how the reported analysis was chosen.
Overall, the available registry information supports a description of the study’s design, endpoint, regimens, and event counts. It does not support a quantitative conclusion about plasma zinc changes or an adjusted comparison among groups. The numerical information needed to judge precision for the primary endpoint is not reported in the registry record.
9. Statistical Methods Explained
The statistical descriptions below distinguish general concepts from details recorded for this study. The registry identifies the primary measure as a mean of a continuous outcome, with standard deviation as its dispersion summary. It does not report the numerical endpoint observations or the model used to analyze them.
What do mean and standard deviation describe?
General explanation: a mean summarizes the central level of a continuous measure across observations. A standard deviation describes how dispersed those observations are around the mean. They answer different questions: the mean concerns the average level, while the standard deviation concerns variability among observations. A standard deviation is not the same as the uncertainty in the estimated mean. That uncertainty depends on the amount and structure of data and on the analysis approach.
For this study, the endpoint description says plasma zinc was measured daily during the 7-day study period in each group. The record does not provide the daily means or standard deviations. It also does not state whether the analysis used each daily measurement separately, summarized change from an initial measurement, or modeled the full within-participant pattern. Those choices matter because measurements from the same participant are generally related rather than independent. This is a general statistical consideration, not a claim about the method used in this study.
Why does the non-randomized design matter?
General explanation: random assignment is intended to make the groups comparable, on average, with respect to characteristics that may affect outcomes. In a non-randomized study, that protection is not guaranteed. Differences in participant characteristics, care, or the process used to assign groups may contribute to observed outcome differences. Statistical adjustment can sometimes address measured differences, but it cannot automatically resolve unmeasured confounding. The registry record does not report an adjustment model or enough allocation details to assess whether such methods were used.
The registry explicitly characterizes the study as non-randomized and cautions that the arms are not a like-for-like control comparison. This is important context for any interpretation, not a numerical correction that can be applied to the posted counts. The record does not report baseline group summaries in the registry record, so the extent of any initial differences is unknown.
What does a confidence interval ordinarily add?
General explanation: a confidence interval expresses the statistical uncertainty around an estimate under a specified method and its assumptions. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. A confidence interval does not remove bias from non-random allocation, and it does not by itself show whether an estimate is clinically important. No confidence interval for the primary endpoint is reported in the registry record. Without an estimate and an interval, the precision of any plasma zinc comparison cannot be evaluated.
How should repeated measurements be considered?
General explanation: repeated measurements can provide information about change over time, but observations from the same person tend to be correlated. An analysis that treats all measurements as independent may misstate uncertainty if that correlation is ignored. Common approaches can model the time course or account for within-person dependence, but the registry record does not identify which, if any, approach was used. It does not state whether baseline concentration was included, how time was represented, or how incomplete daily measurements were handled.
Daily measurement also raises questions about the target comparison. A study might focus on a value at a particular time, an average across the observation period, or an overall trajectory. These are general possibilities, not reported analysis choices for this study. The primary endpoint title and description say plasma zinc concentration over time and daily measurement during 7 days; a specific summary contrast or primary time point is not reported in the registry record.
What do the sample-size assumptions mean?
The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. It also states that time-to-event illustrations use the total number of events under the Schoenfeld method, while other illustrations use participants per arm. These are planning assumptions, not a description of the trial’s actual allocation or an observed outcome.
General explanation: a planning calculation estimates the number of participants needed for a chosen design and target effect under specified assumptions. A calculation based on an observed effect is sensitive to that effect estimate and should be interpreted as an illustration rather than a guarantee. It is not observed power, and it does not show that the study had adequate power for its endpoint. The trial’s own sample-size justification is not reported in the registry record. Numerical planning counts and a numerical observed effect are not reported in the registry record available for this account.
The normal approximation and equal-allocation assumptions describe the illustration’s setup. They should not be mistaken for a claim that participants in the completed study were randomized or equally allocated between two arms. The registry describes non-randomized allocation and lists a control group plus three dose groups. The planning assumptions therefore do not resolve the design limitations or establish the precision of the endpoint findings.
What can be inferred from the analysis listing?
The registry lists 3 outcome measures and 1 analysis. It also identifies glucose homeostasis as a secondary outcome. These counts do not specify the statistical model, the contrast tested, the handling of multiple outcomes, or whether the analysis was adjusted. In general, an analysis count is not a substitute for a complete statistical analysis plan. Details on model choice, covariates, hypothesis tests, and uncertainty estimates are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures, identifies plasma zinc concentration over time as the primary outcome, and lists glucose homeostasis as a secondary outcome. It records 1 analysis. The method used for that analysis and the relationship between the listed outcomes are not reported in the registry record. It is also not reported whether multiple comparisons, multiple time points, or dose-group contrasts were planned and how they would be handled.
General explanation: when an analysis examines multiple outcomes, time points, or group contrasts, the chance of at least one apparently unusual result can increase if each is tested separately. A prespecified testing strategy can clarify which comparisons are primary and how multiplicity is addressed. No such strategy is reported in the registry record, so readers cannot determine whether any statistical adjustment or hierarchical testing plan was used.
Missing-data handling is also not reported in the registry record. The endpoint description indicates daily measurement during the 7-day period, but it does not say whether every participant contributed measurements on every day, how missing values were treated, or whether the analysis used all available observations. The record does not describe imputation, exclusions, or sensitivity analyses for missing primary-outcome data.
The analysis population is not reported in the registry record. The record does not specify whether the endpoint analysis included all enrolled participants, only participants with measurements, or another defined group. Nor does it state how participants who did not complete the intended regimen or measurement schedule were handled. These omissions limit assessment of possible selection and missing-data bias. They do not establish that data were missing or that a particular analysis population was used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Control Group | 0 | 6 | 0.0% |
| Low Dose Group | 1 | 6 | 16.7% |
| Medium Dose Group | 0 | 6 | 0.0% |
| High Dose Group | 0 | 6 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Control Group | 0 of 6 |
| Low Dose Group | 0 of 6 |
| Medium Dose Group | 0 of 6 |
| High Dose Group | 0 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Control Group | Low Dose Group | Medium Dose Group | High Dose Group |
|---|---|---|---|---|---|
| Refractory hypoxemia | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
Serious events with the highest arm-level rate: refractory hypoxemia (16.7%).
The registry reports serious adverse-event counts for each group, with 6 participants at risk in each. The control group has 0 affected, the low-dose group has 1 affected, the medium-dose group has 0 affected, and the high-dose group has 0 affected. For other adverse events, 0 participants are listed as affected in each group. Death counts are not reported in the registry record.
The registry lists refractory hypoxemia as the top serious adverse-event term at 16.7%. The group-level counts and this event-term listing describe recorded safety data; the record does not establish a causal relationship between the event and zinc supplementation. A count in one group, especially in a small study, cannot by itself distinguish a treatment-related event from an event associated with critical illness or other factors. The record does not provide further event timing, severity details, or attribution information in the registry record for this analysis.
These are descriptive counts, not a comparative estimate of risk. Because allocation was non-randomized and the groups are not a like-for-like control comparison, differences in the counts should not be interpreted as a causal contrast. Zero recorded events in a group does not establish that the underlying risk is zero.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed, non-randomized study was designed to examine intravenous zinc supplementation in critically ill children, with plasma zinc concentration over time as the primary endpoint. It identifies a control group and low-, medium-, and high-dose zinc sulfate regimens, and it gives group-level serious and other adverse-event counts. The record also states the study’s purpose: assessing safety and determining an appropriate supplementation dose.
However, the primary outcome description is not accompanied by numerical plasma zinc results in the registry record. There are no group-level means or standard deviations, daily concentration estimates, or reported comparisons in the information available for this account. Therefore, the observed plasma zinc pattern, its magnitude, and its statistical precision cannot be characterized. The registry information does not support a numerical conclusion about change over time or differences by dose.
The safety entries are likewise limited. They describe one serious adverse event recorded in the low-dose group and none in the other groups, with no other adverse events listed as affecting participants. The record does not provide a causal assessment, and the non-randomized design prevents the event counts from serving as a straightforward treatment-versus-control estimate. The death counts are not reported in the registry record.
General interpretation: a study’s stated purpose and design indicate what it set out to investigate, while conclusions depend on the actual estimates, uncertainty, and analysis details. Here, key outcome results, analysis methods, missing-data procedures, and analysis populations are not reported in the registry record. The study description can therefore be read as a record of the question and design, but not as a complete quantitative account of the primary endpoint. It does not establish that zinc supplementation is effective or ineffective, nor does it settle the appropriate dose.
13. Why This Trial Matters Statistically
This study is statistically notable because it combines a dose-escalation question with repeated measurement of a continuous biological outcome in a non-randomized parallel-group design. The endpoint was plasma zinc concentration measured daily during the 7-day study period, summarized in the registry as a mean with standard deviation. Such a design raises distinct questions about change over time, within-participant correlation, and comparisons across dose groups.
The non-randomized allocation is central to interpretation. A control group can provide context, but it does not automatically provide an unbiased counterfactual when group assignment is not random. Potential differences between participants or allocation processes may contribute to any observed contrast. This is why the registry’s caution that the arms are not a like-for-like control comparison is important when assessing claims based on group differences.
The record also illustrates the distinction between a study’s stated aims and the evidence available for evaluating those aims. Safety and dose selection are described as purposes, but the primary concentration results and analysis details are not reported in the registry record. Event counts provide a limited descriptive view, yet they cannot replace the missing endpoint estimates or establish causation.
For researchers, the record underscores the value of transparent reporting of group-level outcome summaries, uncertainty intervals, analysis methods, missing-data handling, and analysis populations. Such information helps readers understand what was estimated and how much confidence to place in it. The planning assumptions described in the record also illustrate why a planning calculation must be distinguished from observed results and from a justification for the completed design.
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.
The main limitation for interpreting the primary endpoint is that numerical plasma zinc results are not reported in the registry record. The daily group means and standard deviations, any baseline values, between-group estimates, and uncertainty intervals are not available in the registry record used for this account. As a result, the endpoint’s observed pattern and precision cannot be assessed.
The study was non-randomized, and the registry itself cautions that the groups are not a like-for-like control comparison. The allocation procedure and baseline group characteristics are not reported in the registry record. This prevents an assessment of how comparable the groups were before the intervention and whether any adjustment addressed differences.
The statistical plan is not described in sufficient detail to evaluate the analysis. The model for repeated measurements, selected contrasts, covariate adjustment, multiplicity approach, missing-data handling, and analysis population are not reported in the registry record. The record’s count of 1 analysis does not clarify these methodological choices.
The safety information is also limited to counts and a listed serious-event term. The registry does not provide death counts, event attribution, or further detail about timing in the registry record for this account. The small group-level counts and non-randomized design mean that descriptive differences cannot establish a causal safety comparison. These limitations concern what can be concluded from the registry record; they do not show that an unreported method or result was absent from other study materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Dose Escalation Study of Zinc Supplementation in Critically Ill Children — NCT01062009.
- Registry record last updated 2019-08-20; status last verified 2019-08.
- Results first posted 2019-08-20.
- 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.
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18. Record Summary
The registry record describes a completed Phase 1 and Phase 2, non-randomized, unmasked, parallel-group study of intravenous zinc sulfate in critically ill children. Enrollment was 24. The groups were control with no intervention, low dose at 250 mcg/kg/day, medium dose at 500 mcg/kg/day, and high dose at 750 mcg/kg/day; the zinc regimens were given for 7 days.
The primary endpoint was plasma zinc concentration over time, measured daily during the 7-day study period and described using a mean and standard deviation. The record lists glucose homeostasis as a secondary outcome. Numerical plasma zinc results and detailed statistical methods are not reported in the registry record.
Serious adverse events were recorded for 6 participants at risk in each group: 0 affected in control, 1 in low dose, 0 in medium dose, and 0 in high dose. No participants were listed as affected by other adverse events. Death counts are not reported in the registry record.