Nebulized Magnesium Sulfate in Children With Moderate to Severe Asthma Exacerbation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nebulized Magnesium Sulfate in Children With Moderate to Severe Asthma Exacerbation (NCT01515995), a randomized phase 4 study. The primary outcome is Change in Forced Expiratory Volume in One Second (FEV1) %.

2. Clinical Question

The trial focuses on the vehicle used to deliver albuterol, rather than comparing albuterol with no albuterol: both arms received the same stated albuterol dose and volume over the same treatment period, while the nebulized solution differed. The primary outcome was change in forced expiratory volume in one second (FEV1), measured by bedside spirometry before and after the intervention.

The registry reports mean changes of 3.6 for the magnesium sulfate group and 5.0 for the normal saline group. Each estimate has a 95% confidence interval. These are separate group summaries; the record does not report a direct between-group estimate or a statistical test. It also marks the two-arm comparison as not estimable for this continuous endpoint. Consequently, the posted group estimates alone do not answer whether the observed changes differed statistically between the treatment groups.

The question addressed is therefore narrower than whether either regimen is effective in clinical care. The record describes a randomized comparison of two albuterol vehicles and reports group-level FEV1 changes over one hour. It does not report a comparative effect estimate, additional outcome results, or a broader assessment of clinical outcomes.

3. Trial Design

This was a completed, randomized, parallel-group, triple-masked phase 4 trial sponsored by the University of Texas Southwestern Medical Center. The registry lists enrollment of 50 participants, a start date of 2012-01, and primary completion in 2015-10. The condition listed is asthma. The study objective was to evaluate nebulized magnesium sulfate as a vehicle for albuterol in children with moderate to severe asthma exacerbation.

Participants were assigned to one of two nebulized regimens. The magnesium sulfate group received 15 mg of albuterol in 22 ml of magnesium sulfate solution containing 880 mg of magnesium sulfate over one hour. The normal saline group received 15 mg of albuterol in 22 ml of normal saline over one hour. The stated contrast is thus between the solutions used as the vehicle for the albuterol. The registry record does not report additional treatment details or the procedures used to maintain masking.

The primary outcome was change in FEV1 percentage, measured by bedside spirometry at baseline and one hour after treatment. The registry lists one outcome measure and no posted analysis entries. For this outcome, it reports 22 participants in the magnesium sulfate group and 21 in the normal saline group. These outcome-specific counts do not by themselves explain how the enrolled participants relate to the reported outcome groups; reasons for any difference are not reported in the registry record.

Randomization supports a planned comparison between groups, while the parallel design means participants were assigned to one group rather than crossing between regimens. Masking can reduce the influence of expectations on care or assessment in general, but the registry does not identify who was masked or describe how masking was implemented. Although the trial is marked completed, completion status alone does not establish that all planned analyses or all results were posted.

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

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 Change in Forced Expiratory Volume in One Second (FEV1) %, measured over Baseline and one hour after treatment.

The primary endpoint is change in forced expiratory volume in one second (FEV1) from baseline to one hour after treatment. FEV1 is the amount of air a person can forcibly exhale during the first second of a breathing test. The registry describes measurement by bedside spirometry before and after the study intervention and identifies the outcome unit as percentage of FEV1.

Change from baseline is used to describe how a measured value shifts over a specified period, rather than reporting only a post-treatment measurement. In general, a change score can help readers understand the direction and size of movement within each group during the stated interval. It does not, by itself, isolate a treatment effect: a randomized comparison requires assessing the difference in change between groups, with an estimate of uncertainty for that contrast.

The posted group means are 3.6 for magnesium sulfate and 5.0 for normal saline. Their respective 95% confidence intervals are 0.9 to 6.3 and 1.7 to 8.4. The registry record does not report a direct contrast for these means, and it identifies the two-arm comparison as not estimable. The outcome therefore describes group-level changes, but the posted record does not quantify the comparative change attributable to the differing vehicles.

The one-hour timeframe is specific to this measurement. The endpoint does not, on its own, describe later lung function, symptoms, subsequent treatment, or other clinical outcomes; those results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group trial with triple masking. Randomization is intended, in general, to make treatment groups comparable on average at assignment, including for factors that may not be measured. A parallel design assigns each participant to one study group. Masking can help limit the influence of treatment expectations on assessment or care, although the registry record does not report which parties were masked or the practical masking procedures.

What does the reported mean represent?

The primary outcome is continuous: change in FEV1 percentage from baseline to one hour after treatment. For a continuous measure, a mean is an average of participant-level values. The posted mean change is 3.6 in the magnesium sulfate group and 5.0 in the normal saline group. These means summarize each group; they do not themselves quantify the randomized treatment contrast. The registry record does not specify additional details about the calculation of the change score, such as the exact analysis population or any adjustment for baseline values.

How should the confidence intervals be read?

The registry reports 95% confidence intervals of 0.9 to 6.3 for the magnesium sulfate group and 1.7 to 8.4 for the normal saline group. In general, a confidence interval gives a range of values compatible with the data under the method's assumptions and reflects uncertainty in an estimate. It is not a range containing every participant's result, nor does it directly state the probability that the true value lies in that particular calculated interval. These intervals concern the separate group means, not their difference.

For a randomized comparison, the central inferential quantity would generally be a between-group contrast, such as a difference in mean change, alongside an uncertainty interval and, where appropriate, a test. The registry record does not report that contrast or its interval. It marks the two-arm comparison as not estimable for this continuous endpoint. It is therefore not appropriate to derive a comparative effect by subtracting the posted means or to use the separate confidence intervals as a substitute for a direct analysis.

What does non-estimable mean in this record?

Here, the registry's stated reason is that values are missing or not estimable for a two-arm comparison of the continuous endpoint. This signals a limitation in the posted comparative results; it does not establish why the values were unavailable or what analysis was attempted. The record lists no analysis entries, so the statistical model, handling of participant-level observations, any covariate adjustment, and any inferential procedure are not reported in the registry record.

In general, precision in a group mean and precision in a group contrast are different questions. A group mean can be estimated even when the registry does not furnish a usable comparative estimate. The randomized design describes how groups were assigned, but a design label alone cannot supply the missing analysis result. Without a reported contrast, readers cannot determine its estimated magnitude or precision from the registry results.

How do planning assumptions differ from observed results?

The registry's stated planning convention describes illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not measures of the trial's observed power. A sample-size illustration asks how many participants per arm might be needed under specified assumptions; it does not change the actual enrollment or produce evidence that a result was significant.

Because the record marks the two-arm continuous comparison as not estimable, it does not provide a comparative effect value on which a reader can independently base an interpretation. Specific numerical planning counts are not reported in the registry record. The assumptions alone should not be read as the trial's original design justification: the registry does not report the protocol's sample-size justification or its planned effect size.

Why can over-dispersion matter?

In general, over-dispersion refers to observed variability that is greater than a statistical model assumes. If a model understates variability, its uncertainty estimates can be too small and inferential results can appear more precise than warranted. The registry identifies this endpoint as a continuous measure summarized by means and confidence intervals; it does not report an over-dispersion assessment or a model where that issue is described. This general concept therefore does not establish a problem with the posted FEV1 estimates.

The statistical information available supports a careful description of group-level means and their separate intervals. It does not support a reconstructed treatment contrast, a claim of statistical significance, or a claim of equivalence. Those would require analysis information not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero secondary outcomes posted. It also lists zero analysis entries. The primary outcome is change in FEV1 percentage from baseline to one hour after treatment. The record does not report a broader analysis plan, a hierarchy of outcomes, adjustments for multiple testing, or interim analyses. Their presence or absence in the study protocol is not reported in the registry record.

Multiplicity arises in general when several outcomes, time points, or analyses are tested: repeated opportunities to identify a nominally unusual result can affect the interpretation of statistical evidence. With only one posted outcome measure and no analysis entries, the registry does not provide enough information to assess how the investigators handled multiplicity, if relevant to their planned analyses.

The registry reports endpoint counts of 22 in the magnesium sulfate group and 21 in the normal saline group, while total enrollment is 50. It does not state why those counts differ from enrollment, whether any measurements were missing, how missing measurements were handled, or which analysis population was used. The outcome description names baseline and one hour after treatment, but it does not establish that every enrolled participant had both measurements.

Consequently, the record does not allow readers to assess whether the results were analyzed by assigned group, whether participants were excluded, or whether missing data could have affected the estimates. No missing-data method, sensitivity analysis, or population definition is reported in the registry record. These omissions do not prove that such procedures were absent from the study; they mean their details cannot be evaluated from the posted record.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse-event counts for 25 participants at risk in each group. There were zero participants with a serious adverse event in the magnesium sulfate group and zero in the normal saline group. The registry also reports zero deaths in each group.

For other adverse events, 25 participants were listed at risk in each group. Four participants in the magnesium sulfate group were reported as affected, compared with zero in the normal saline group. The record does not describe the specific events in this category, and it lists no serious adverse-event terms.

These are descriptive counts, not a comparative safety analysis. The registry does not report a statistical test, an adjusted comparison, or further detail about event timing, severity, or attribution. Zero reported serious events in these groups should not be interpreted as proof that serious events cannot occur, and the difference in other-event counts does not by itself establish that the study treatment caused those events. The adverse-event population and denominators should also be kept distinct from the outcome-specific group counts; the registry does not explain their relationship.

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

The posted results show mean one-hour FEV1 changes of 3.6 in the magnesium sulfate group and 5.0 in the normal saline group. The corresponding 95% confidence intervals are 0.9 to 6.3 and 1.7 to 8.4. These figures describe group-level endpoint summaries and uncertainty around each group mean. They do not supply an estimated difference between the groups.

The registry explicitly says that values are missing or not estimable for the two-arm comparison of this continuous endpoint. No analysis entries are posted. As a result, the record does not establish whether the groups differed statistically, how large a comparative effect may have been, or how precisely such an effect could be estimated. It also does not establish that the regimens were equivalent or that no difference existed. A missing comparative result is not evidence for either conclusion.

The outcome is limited to FEV1 change between baseline and one hour after treatment. It does not describe longer-term lung function, symptoms, subsequent care, or other outcomes. The registry lists one outcome measure and no secondary outcome results. The adverse-event record provides counts but not event descriptions or a comparative analysis, so it cannot support a detailed account of the safety profile.

In general, a randomized design is intended to support comparisons between assigned groups, but the relevant comparative analysis must be reported to interpret the treatment contrast. The posted group summaries remain useful as descriptions, yet they cannot replace that analysis. The record's completion status and enrollment do not resolve the missing comparative result or explain the endpoint-specific counts.

The defensible reading is therefore limited: group mean changes and their intervals are reported, while the direct randomized comparison is not estimable in the registry record. Any stronger claim about relative benefit, lack of difference, or causation would go beyond the results posted.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical statistics: reporting a result for each group is not the same as reporting the comparison that a randomized trial is designed to address. The posted means describe the one-hour FEV1 change in each group, and the confidence intervals describe uncertainty around those separate means. The registry does not report a direct estimate of the difference between groups.

That distinction matters because readers can be tempted to infer a treatment contrast by looking at two group summaries. In general, the uncertainty of a difference depends on the variability and precision of both groups and on the analysis used. Separate confidence intervals do not convey that contrast's uncertainty. The registry's explicit non-estimability flag makes this limitation visible rather than leaving readers to mistake descriptive estimates for a comparative result.

The record also demonstrates why transparent reporting of analysis populations and missing-data handling is important. Enrollment is listed as 50, while the primary outcome counts are 22 and 21. The record does not explain the relationship between those counts, so the reason cannot be assessed from the posted information. Likewise, the absence of posted analysis entries leaves the statistical method and the handling of incomplete measurements unknown.

For biostatisticians and clinical researchers, the practical lesson is to distinguish the planned randomized contrast from the summaries that happen to be available. A trial may have a clear intervention, comparator, and endpoint, yet still lack a posted estimate that answers its comparative question. Reporting the estimate, its uncertainty, the analysis population, and missing-data procedures would allow a more complete statistical interpretation.

The safety counts offer another reporting lesson: numerators and denominators provide a basic descriptive frame, but event definitions and comparative methods matter for interpretation. Counts alone should not be converted into causal claims. In this record, both the efficacy comparison and detailed safety interpretation remain limited by what is posted.

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 most important trial-specific limitation in the registry record is the absence of an estimable two-arm comparison for the primary continuous endpoint. Although group means and confidence intervals are posted, no between-group estimate or analysis result is reported. This prevents direct interpretation of the randomized contrast that the study was designed to examine.

The analysis record is sparse: one outcome measure is listed, no secondary outcomes are posted, and there are zero analysis entries. The registry does not report the statistical model, analysis population, covariate adjustments, missing-data approach, or sensitivity analyses. It also does not report the protocol's sample-size justification or planned effect size. These missing details limit assessment of how the reported estimates were produced and how robust they may be.

The endpoint counts are 22 and 21, whereas enrollment is listed as 50. The registry does not report the reasons for the difference or whether measurements were missing, excluded, or unavailable. Without those details, readers cannot assess the extent or possible consequences of incomplete outcome data. The record also does not report further population characteristics or eligibility details beyond children with moderate to severe asthma exacerbation.

The primary outcome is restricted to FEV1 change at one hour. Longer-term outcomes and additional clinical measures are not reported in the registry record. For safety, the record reports event counts but not the kinds of other adverse events, detailed timing, or a comparative statistical analysis. The study's completed status does not fill these reporting gaps, and none of them can be resolved from the posted summaries alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Nebulized Magnesium Sulfate in Children With Moderate to Severe Asthma Exacerbation — NCT01515995.
• Registry record last updated 2019-02-21; status last verified 2019-01.
• Results first posted 2019-02-21.
• 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.

18. Record Summary

NCT01515995 is a completed, randomized, parallel, triple-masked phase 4 trial sponsored by the University of Texas Southwestern Medical Center. It enrolled 50 participants and studied nebulized magnesium sulfate as a vehicle for albuterol in children with moderate to severe asthma exacerbation. The magnesium sulfate arm received 15 mg of albuterol in 22 ml of solution containing 880 mg of magnesium sulfate over one hour; the comparator received 15 mg of albuterol in 22 ml of normal saline over one hour.

The primary outcome was change in FEV1 percentage from baseline to one hour after treatment. The registry reports means of 3.6 and 5.0, with respective 95% confidence intervals of 0.9 to 6.3 and 1.7 to 8.4. It does not report an estimable two-arm comparison or analysis entries. Serious adverse events and deaths were reported as zero in both groups; other adverse events were reported for four participants in the magnesium sulfate group and none in the normal saline group. Further analysis and outcome details are not reported in the registry record.