Treatment of Persistent Pulmonary Hypertension in Neonates With Nebulized Magnesium Sulfate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Persistent Pulmonary Hypertension in Neonates With Nebulized Magnesium Sulfate (NCT06603766), a non-randomized phase 2, phase 3 study. The primary outcome is Mean Airway Pressure (cm H2O).

2. Clinical Question

The clinical question therefore has a defined population, two routes of administration, and a named physiological endpoint, but the available record does not establish what the comparison found. The study is identified as a comparative study, yet it was non-randomized and unmasked. Those design features matter when interpreting any group contrast: the arms may differ in ways other than treatment route, and knowledge of the treatment can influence some aspects of care or measurement. The registry record does not report enough detail to determine whether those risks were addressed in the analysis.

3. Trial Design

The registry describes a completed parallel-group study with non-randomized allocation and no masking. It lists the study as phase 2 and phase 3. Benha University is the sponsor. The recorded study start date is 2021-10-01, and the primary completion date is 2023-09-28. Enrollment is listed as 40. The arm descriptions state n=20 for the NebMag group and n=20 for the IVMag group.

The comparison is between nebulized magnesium sulfate and intravenous magnesium sulfate in neonates with persistent pulmonary hypertension. The nebulized arm is described as receiving nebulized isotonic magnesium at 64 mg/mL. The intravenous arm description includes a 10% magnesium sulfate solution and a loading dose of 2 mL/kg over 30 minutes, equivalent to 200 mg/kg of magnesium sulfate. Both arm descriptions in the registry record are incomplete, so the full treatment schedules and any additional treatment details are not reported in the registry record.

Non-randomized allocation means that assignment was not described as being determined by chance. As a general statistical concern, treatment groups formed this way can differ at baseline in prognostic factors, care circumstances, or other characteristics. If such differences are related to the outcome, a raw comparison may combine treatment-route differences with those other influences. The registry record does not report how participants were assigned or whether the analysis adjusted for baseline differences.

The record identifies mean airway pressure as the primary outcome, assessed from baseline to 12 and 24 hours after administering the study drug. It also names variations in mean arterial blood pressure and alterations in serum magnesium levels as secondary outcomes. The record lists six outcome measures and six analyses, but does not describe all of them in the available information. It reports the study status as completed, but completion does not by itself indicate that results were posted or that the primary comparison can be evaluated.

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: The total number of neonates who admitted at Benha University hospital diagnosed as PPHN during study period was 158. 95 was excluded as they did not meet inclusion criteria. 23 parents refused to participate in the study.

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 Mean Airway Pressure (cm H2O), measured over from baseline to 12 and 24 hours after administering the study drug.

Mean airway pressure, measured in cm H2O, is the primary endpoint. The registry specifies a mean as the summary measure and standard deviation as the dispersion measure. Measurements are described at baseline and at 12 and 24 hours after administration of the study drug. The endpoint therefore concerns a continuous physiological measurement observed over time, rather than a binary event such as whether a participant experienced an event.

In general, airway pressure measures can characterize the pressure used during respiratory support. Following the measure over time can describe its course after treatment administration, while comparing groups can address whether their observed courses differ. The registry record does not define a particular contrast, such as change from baseline at each follow-up or an overall comparison across follow-up times. It also does not report the measurement procedure, the analysis population, or whether the primary comparison focused on one follow-up time or both.

A mean describes the group’s average value, while a standard deviation describes the spread of individual observations around that average. These summaries can help readers understand both the typical level and variability, but neither is reported by arm for the primary endpoint in the registry record. Without the actual measurements or estimates, the endpoint definition alone cannot indicate the direction, size, or precision of any group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous, and the registry identifies the mean and standard deviation as its summary statistics. The endpoint is mean airway pressure at baseline and at 12 and 24 hours after study drug administration. The statistical methods used to analyze these observations are not reported in the registry record. The general explanations below describe how such data are commonly interpreted; they do not establish which methods this study used.

What does a mean and standard deviation describe?

General: The mean is the arithmetic average of the observed measurements in a group. The standard deviation describes how dispersed those measurements are around the group mean. A mean can provide a compact description of the group’s central level, while the standard deviation conveys variation among observations. The mean and standard deviation do not show the full distribution, and they do not by themselves indicate how precisely a group difference has been estimated. For that, an estimate’s standard error or confidence interval is useful.

The registry’s designation of a mean and standard deviation identifies a reporting format for the continuous endpoint. It does not state whether the primary analysis compared follow-up values, changes from baseline, or trajectories across the measurement times. Those choices can target different quantities. The precise contrast and model are not reported in the registry record.

Why does the repeated measurement structure matter?

General: Measurements taken from the same participant over time are usually correlated. A participant’s later value may be related to that participant’s baseline value, so treating every measurement as if it came from a different person can misrepresent the uncertainty. Repeated-measures methods can account for within-participant correlation and can estimate changes over time or differences in trajectories, depending on how the model is specified.

Baseline and post-administration values can also be handled in different ways. An analysis might compare follow-up values between groups while accounting for baseline, compare changes from baseline, or model observations over time together. These approaches require clear definitions of the target contrast and assumptions about the data. The registry record does not report which approach was used, how correlation was handled, or whether one follow-up time was prioritized over the other.

What does a confidence interval contribute?

General: A confidence interval expresses uncertainty around an estimated quantity under a specified statistical model and its assumptions. For a between-group contrast, it gives a range of values that are compatible with the observed data and method. Its width depends on factors such as variability, the amount of available information, and the analysis. A narrow interval indicates greater precision than a wide interval, but precision is not the same as importance.

No confidence interval or effect estimate for mean airway pressure is reported in the registry record. Accordingly, the size and precision of the primary contrast cannot be assessed. The standard deviations named in the endpoint description would help characterize variability if reported, but they would not substitute for a between-group estimate and its uncertainty.

How should a p-value be understood?

General: A p-value describes how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the probability that a result is due to chance in a broad, assumption-free sense. A small p-value does not establish that a difference is large or important, while a larger p-value does not establish that groups are equivalent. Interpretation should consider the estimated contrast, its confidence interval, design limitations, and the analysis plan.

No p-value for the primary endpoint is reported in the registry record. The record also does not state the significance threshold, whether tests were one- or two-sided, or which analysis generated the primary result. A significance test therefore cannot be reconstructed from the available outcome information.

Why is allocation relevant to the analysis?

General: Random allocation can help balance measured and unmeasured prognostic factors across groups on average. In a non-randomized study, group differences may instead reflect how treatment was selected or assigned. Statistical adjustment can address measured differences when relevant variables are available and the model is appropriate, but adjustment cannot guarantee removal of bias from unmeasured factors or poor measurement. The registry identifies allocation as non-randomized; it does not report the allocation process, baseline comparisons, covariates, or adjusted estimates.

These issues affect what a group contrast can support. A comparison can describe outcomes among the observed groups, while a causal interpretation requires stronger assumptions about comparability and confounding. The registry record does not report a causal estimand or the methods and assumptions used to support a causal claim. The available record therefore supports description of the study question and design, not a causal result.

What can planning calculations tell readers?

General: A sample-size planning calculation asks how much information a future study might need to detect a specified effect under stated assumptions. The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. Such planning quantities are hypothetical design illustrations, not observed outcomes and not evidence of the probability that this completed study detected an effect.

The numerical planning results and the observed effect used in those calculations are not reported in the registry record. The record does not report the trial’s own sample-size justification. No sample-size planning illustration can replace an observed treatment contrast with uncertainty, and it should not be interpreted as observed power.

10. Multiplicity, Missing Data and Analysis Populations

The record lists six outcome measures and six analyses. It names mean airway pressure as the primary outcome and identifies variations in mean arterial blood pressure and alterations in serum magnesium levels as secondary outcomes. The relationship between all listed measures and analyses is not reported in the registry record. The registry record also does not report a multiplicity strategy, such as whether selected outcomes or time points were treated as confirmatory or whether any adjustment was planned for multiple comparisons.

General: When many outcomes, time points, or statistical tests are considered, the chance of obtaining at least one apparently notable result can increase. Multiplicity procedures can control a specified error rate, but they may affect interpretation and precision. Without the analysis plan and results, it is not possible to determine what multiplicity concerns applied or how they were handled in this study. The count of listed analyses alone does not establish that each analysis was an independent hypothesis test.

Missing-data methods and the extent of missing outcome measurements are not reported in the registry record. The record does not state whether all enrolled participants contributed to each endpoint, how incomplete follow-up was handled, or whether any imputation or sensitivity analysis was used. General: Missingness can affect estimates when the likelihood of an unavailable measurement is related to participant characteristics or outcomes. The consequences depend on the pattern and reasons for missingness and the assumptions used in analysis.

The analysis population is not reported in the registry record. It is therefore unclear whether the primary analysis included all enrolled participants, only participants who received treatment, or another defined group. The record also does not describe exclusions, protocol deviations, or the handling of participants with incomplete measurements. These omissions limit assessment of both bias and reproducibility.

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 0% reporting threshold.

The registry reports 0 serious adverse events, 0 other adverse events, and 0 deaths for the NebMag group, with 20 participants listed at risk in each adverse-event category. For the IVMag group, it likewise reports 0 serious adverse events, 0 other adverse events, and 0 deaths, with 20 participants listed at risk in each category. These are the safety counts recorded for the two groups.

These entries should be read narrowly: the registry record reports no affected participants in the listed categories. They do not establish that no adverse events occurred outside the definitions or reporting period used, nor do they demonstrate the absence of risk. The record does not report the definitions used for serious or other adverse events, the duration or completeness of safety follow-up, or detailed event narratives. It also does not explain how events were collected or adjudicated.

General: Zero recorded events in a study does not imply that the underlying event risk is zero. The amount of information available for evaluating uncommon events depends on study size, follow-up, event definitions, and reporting completeness. The registry counts can describe what was recorded, but they cannot, on their own, establish comparative safety or rule out harms that were not observed or reported.

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

The record establishes that a completed, non-randomized, unmasked parallel-group study compared nebulized with intravenous magnesium sulfate in neonates with persistent pulmonary hypertension. Mean airway pressure from baseline to 12 and 24 hours after study drug administration was designated as the primary endpoint. The record also names mean arterial blood pressure and serum magnesium levels as secondary outcomes.

Those details describe the research question and design, not the treatment effect. Arm-specific outcome values, between-group estimates, confidence intervals, and p-values are not reported in the registry record. It is therefore not possible to determine from the registry whether the groups differed in mean airway pressure, how large any difference was, or how precisely it was estimated. Results for the named secondary outcomes are also not reported.

The non-randomized design is important because the groups may not have been comparable at baseline. In general, observed differences can reflect treatment, pre-existing group differences, other care, or a combination of factors. The registry record does not report the allocation process, baseline characteristics, or adjustment methods needed to evaluate those possibilities. The unmasked design is another consideration, although the record does not describe whether or how lack of masking could have influenced outcome measurement or care.

The safety counts report 0 serious adverse events, 0 other adverse events, and 0 deaths in each group. These are registry entries, not proof of no risk or evidence of equivalent safety. Definitions, follow-up completeness, and event-collection procedures are not reported in the registry record.

In general, a treatment comparison is most informative when the endpoint estimate, its uncertainty, the analysis population, and the assumptions behind the analysis are clear. For this study, the record documents the design and endpoint but not the outcome results needed to judge the observed comparison. It supports neither a conclusion that one route is better nor a conclusion that the routes are equivalent.

13. Why This Trial Matters Statistically

This trial is statistically notable as a comparison of two administration routes conducted without random allocation. That design can be useful for documenting a clinical question and observed outcomes, but it requires careful attention to comparability between groups. General: In randomized studies, chance assignment helps reduce systematic differences on average; in non-randomized studies, treatment choice or assignment can be related to prognosis. The resulting comparison needs transparent information on baseline characteristics and analysis methods to help readers assess confounding.

The endpoint also has a time structure: mean airway pressure is specified at baseline and at 12 and 24 hours after administration. General: Repeated measurements can capture change over time, but they are correlated within participants. A clear analysis plan should state how time is handled, what contrast is primary, and how incomplete follow-up is treated. Those details are not reported in the registry record, so the endpoint specification does not fully define the statistical estimand.

The record lists six outcome measures and six analyses, making it important to know which comparisons were planned as primary and how multiple outcomes or time points were interpreted. The registry identifies mean airway pressure as primary and names two secondary outcomes, but does not report the broader analysis plan or multiplicity approach. Nor does it report endpoint estimates or their uncertainty.

For clinical researchers, the central statistical lesson is that an outcome definition and a completed status are not substitutes for posted results. A transparent report needs estimates, measures of precision, participant flow, missing-data information, and sufficient design detail to understand how the comparison was conducted. The available record identifies the subject of the trial but does not provide those elements for evaluating efficacy or comparative safety.

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.

Several limitations specific to this trial can be identified from the registry record. Allocation is described as non-randomized, so the groups may not have been comparable before treatment. The allocation process and baseline characteristics are not reported in the registry record. Without those details, readers cannot assess potential confounding or determine whether an adjusted analysis addressed measured differences.

The study is also described as unmasked. The registry record does not explain who knew treatment assignment, how airway pressure measurements were collected, or whether outcome assessment was independent of treatment. These missing details make it difficult to evaluate the potential influence of knowledge of treatment on care or measurement.

Although the primary endpoint and assessment times are specified, outcome results are not reported in the registry record. Arm-specific means and standard deviations, between-group estimates, confidence intervals, and p-values are absent. The record does not report how the repeated measurements were modeled or which contrast was the main comparison. Results for the secondary outcomes are also not reported.

The registry record does not report eligibility criteria, participant characteristics, participant flow, missing-data handling, or the analysis population. It lists six outcome measures and six analyses but does not provide a full statistical analysis plan or multiplicity approach. The arm descriptions give some preparation and dosing details, but the full administration regimens are not reported in the registry record.

Finally, safety entries list 0 events in the categories reported, but event definitions, follow-up duration, and reporting completeness are not described. These gaps mean the safety counts should be interpreted as registry reporting rather than as a comprehensive estimate of risk. Together, these limitations prevent a detailed assessment of the treatment comparison from this record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of Persistent Pulmonary Hypertension in Neonates With Nebulized Magnesium Sulfate — NCT06603766.
• Registry record last updated 2025-02-05; status last verified 2025-02.
• Results first posted 2025-02-05.
• 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

The registry record describes a completed, non-randomized, unmasked parallel-group study sponsored by Benha University. It is listed as phase 2 and phase 3, with enrollment of 40. The comparison is nebulized versus intravenous magnesium sulfate for persistent pulmonary hypertension in neonates. Mean airway pressure, measured from baseline to 12 and 24 hours after study drug administration, is the primary endpoint; mean arterial blood pressure and serum magnesium levels are named as secondary outcomes.

The record lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each group. It does not report primary or secondary outcome estimates, confidence intervals, p-values, the analysis population, missing-data methods, or a full statistical analysis plan. The design and endpoint are described, but the posted registry information is insufficient to assess the comparative outcome results.