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 Dornase Alfa for ARDS in Patients With Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) (NCT04402970), a non-randomized phase 3 study. The primary outcome is Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04402970 |
| Phase | Phase 3 |
| Condition | SARS-CoV 2, ARDS |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Missouri-Columbia |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes patients with SARS-CoV-2 infection, ARDS based on Berlin criteria, and respiratory failure requiring mechanical ventilation. The primary endpoint population is narrower: patients still on mechanical ventilation who underwent arterial blood gas monitoring to determine the PaO2/FiO2 ratio. Eligibility details beyond the registry description are not reported in the registry record.
Intervention
Patients in the intervention arm were to receive inhaled or nebulized dornase alfa, also identified as Pulmozyme, at 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. The study rationale describes dornase alfa as degrading cell-free DNA, with the aim of addressing airway mucus and neutrophil extracellular traps.
Comparator
The comparator arm received standard of care for ARDS. Allocation was non-randomized, so the arms are not a like-for-like control comparison. The registry does not report how treatment assignment was determined, and differences between the groups may reflect factors other than the intervention.
Primary question
The primary question concerns change in the arterial oxygen content to fraction of inspired oxygen ratio, PaO2/FiO2, over 14 days. The registry specifies daily evaluation at baseline before therapy and on days 1, 2, 3, 4, 5 and 14, if applicable. It does not report the observed group results, an estimated between-group contrast, or an analysis of this endpoint. The record therefore describes the question the study set out to examine, but does not establish what the posted data show about oxygenation.
3. Trial Design
This is a completed Phase 3 study registered as NCT04402970, sponsored by the University of Missouri-Columbia. The registry records an enrollment of 30 and gives a study start date of 2020-06-19 and a primary completion date of 2020-12-31. The brief summary separately says investigators aimed to recruit 10-20 patients. The record does not explain the relationship between that stated recruitment aim and the enrollment entry.
The design is parallel, with an inhaled or nebulized dornase alfa arm and a standard-of-care arm. The intervention arm received dornase alfa with standard care, whereas the comparator arm received standard care. Allocation is recorded as non-randomized. The registry also records single masking, but does not identify who was masked or describe how masking was maintained.
Because assignment was not randomized, the groups should not be interpreted as if treatment allocation had balanced measured and unmeasured characteristics. Any differences in outcomes could reflect treatment, baseline differences, clinical decisions, or other influences. The registry does not report the allocation process, baseline characteristics, or an adjusted analysis that might address group differences.
The primary outcome is change in PaO2/FiO2 over 14 days, with repeated daily assessment at specified times when applicable. Secondary outcomes listed include static lung compliance, duration of mechanical ventilation, ICU stay, hospitalization, secondary bacterial infections, and mortality. The registry marks the study as completed, but reports no analyses and no primary endpoint estimates.
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
| Stage | Inhaled/Nebulized Dornase Alfa | Standard of Care |
|---|---|---|
| STARTED | 10 | 20 |
| COMPLETED | 10 | 20 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Number of patients still on mechanical ventilation and who underwent arterial blood gas monitoring to determine PaO2/FiO2 ratio
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 | Inhaled/Nebulized Dornase Alfa | Standard of Care | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 20 | 30 | |
| Age, Continuous | years | 62 (47 to 79) | 58 (24 to 84) | 60 (24 to 84) |
| Sex: Female, Male: Female | Participants | 4 | 7 | 11 |
| Sex: Female, Male: Male | Participants | 6 | 13 | 19 |
| Race/Ethnicity, Customized: White, non-Hispanic | Participants | 8 | 16 | 24 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 2 | 3 | 5 |
| Region of Enrollment: United States | participants | 10 | 20 | 30 |
| Diabetes mellitus | Participants | 7 | 11 | 18 |
| Hypertension | Participants | 9 | 14 | 23 |
| Coronary artery disease | Participants | 5 | 7 | 12 |
| Chronic lung disease (COPD, asthma, ILD) | Participants | 3 | 7 | 10 |
| Obesity | Participants | 8 | 17 | 25 |
| Remdesivir | Participants | 9 | 20 | 29 |
| Corticosteroids | Participants | 9 | 20 | 29 |
| Antibiotics | Participants | 10 | 19 | 29 |
| Convalescent Plasma | Participants | 9 | 11 | 20 |
| Anticoagulation | Participants | 4 | 10 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2), measured over 14 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in the PaO2/FiO2 ratio, reported in mmHg. This ratio relates the oxygen measured in arterial blood to the fraction of oxygen being delivered in inspired air. As a general statistical and clinical concept, tracking it over time can describe changes in oxygenation during respiratory illness and treatment; it is not, by itself, a complete measure of recovery or overall clinical outcome.
The registry specifies a mean as the summary measure and a 95% confidence interval as the dispersion measure. Assessment was planned at baseline before therapy and on days 1, 2, 3, 4, 5 and 14, if applicable. The primary endpoint population is described as patients who remained on mechanical ventilation and underwent arterial blood gas monitoring to determine the ratio. This conditional population matters: measurements may not be available at every time point for every participant, and the record does not explain how such unavailable assessments were handled.
A confidence interval is a statistical way to express uncertainty around an estimate. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. No mean changes, confidence interval bounds, or endpoint comparison are reported in the registry record, so the magnitude and precision of any observed change cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study question and design, but does not report the primary endpoint results. It names change in PaO2/FiO2 as the primary outcome and gives its measurement schedule and target population. It provides no observed means, confidence intervals, between-arm estimate, or statistical test for that endpoint. Consequently, the record does not show the direction, size, or precision of any oxygenation change.
The non-randomized allocation is central to interpretation. Random assignment is a design method intended to make comparison groups similar on average, including for characteristics that may not be measured. This study did not use random allocation. The registry explicitly cautions that the arms are not a like-for-like control comparison. Even if outcome values were reported, a difference between these groups would not automatically isolate an effect of dornase alfa. Treatment assignment could be associated with illness severity, clinical judgment, timing, or other characteristics; the assignment process and baseline comparability are not reported.
The intervention was added to standard care, whereas the comparator received standard care. The intended comparison is therefore not dornase alfa versus no care. The record describes a mechanistic rationale involving cell-free DNA and neutrophil extracellular traps, as well as a clinical aim involving oxygenation and recovery. A rationale is not an observed result. The registry does not report whether the proposed biological pathway changed, and it does not provide results for the listed secondary outcomes.
The study is marked completed, and enrollment is recorded as 30. Completion status and enrollment do not supply evidence about the primary outcome. The brief summary’s recruitment aim of 10-20 differs from the enrollment entry; the registry does not explain this difference. No analyses are listed. Thus, the posted record does not permit an assessment of statistical significance, the size of an association, or how precisely an estimate was measured.
In general, estimates and confidence intervals are needed to understand both magnitude and uncertainty. A result can be imprecise even when a point estimate is available, and statistical significance alone would not establish clinical importance. Here, there is no primary estimate or interval to interpret. The defensible conclusion is limited to what the registry reports about the study’s design, intended measurements, and recorded safety counts—not a conclusion that the intervention improved or failed to improve outcomes.
9. Statistical Methods Explained
The registry identifies the primary measure as a continuous outcome summarized by a mean, with a 95% confidence interval. In general, a mean describes the average value in the analyzed observations. A confidence interval communicates uncertainty around an estimated mean or contrast under the assumptions of the analysis. It is not a range expected to contain most individual patients’ measurements, and it does not remove bias that may arise from non-random treatment assignment.
What does repeated measurement mean for this endpoint?
PaO2/FiO2 was to be assessed at baseline and on several later study days, if applicable. Repeated measurements from the same patient are statistically related: a person’s values over time are not independent observations. General methods for longitudinal data account for this within-person relationship and can estimate change over time while using the available measurements. The registry record does not report which method, if any, was used, how time was represented in a model, or whether the principal comparison was a change from baseline, a comparison at a particular time, or an overall time-course contrast.
The primary population is defined by continued mechanical ventilation and arterial blood gas monitoring. In general, this type of population definition can make the analyzed group differ from everyone enrolled. Whether a patient remains ventilated and receives testing may relate to clinical status or care decisions. The registry does not report the number assessed at each time point, reasons for unavailable measurements, or how those missing observations were treated. It also does not report whether the analysis included every enrolled participant or a defined subset.
How should the non-randomized comparison be read?
With non-randomized allocation, groups may differ before treatment begins. Statistical adjustment can sometimes account for measured baseline characteristics, but it cannot guarantee removal of confounding, particularly from unmeasured or poorly measured factors. This is a general limitation of observational comparisons, not a finding about a particular imbalance in this study. The registry does not report baseline group summaries, an adjustment set, or an adjusted primary analysis. It therefore offers no basis for judging whether any analysis addressed group differences.
Single masking is recorded, but the person or people masked are not specified. In general, masking may reduce the influence of knowledge of treatment assignment on assessments or decisions, depending on who is masked and how the procedure is implemented. The record does not describe implementation or state whether outcome assessors were masked. The masking entry alone is not enough to determine how much risk of assessment bias was reduced.
What can be said about statistical planning?
The registry describes a sample-size planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is described as detecting a stated fraction of the observed effect. No numerical sample-size outputs or observed effect are included in the record. Such planning values, when available, are illustrations of the sample size associated with specified assumptions; they are not observed power and do not show that a study had a particular probability of detecting a true effect.
The analysis count is recorded as zero, and the registry does not report the statistical analysis plan, a primary result, or a hypothesis test. The use of a 95% confidence interval as the stated dispersion measure does not identify the model used to calculate it. The record also does not specify whether estimates were adjusted, how multiple time points were handled, or whether any interim analysis occurred.
Why does over-dispersion matter in general?
For count outcomes, over-dispersion means that variability is greater than a simple model assumes. If ignored, uncertainty can be understated and statistical tests can be too optimistic. This general issue does not establish that over-dispersion occurred in this study. The primary endpoint is continuous, and the registry does not report a statistical model for it or methods for any count-based secondary outcomes. No specific model assumptions can therefore be evaluated from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and secondary outcomes covering lung compliance, mechanical ventilation, ICU stay, hospitalization, secondary bacterial infections, and mortality. Examining multiple outcomes or multiple time points can raise a general multiplicity issue: the more comparisons considered, the greater the chance that at least one appears noteworthy by chance alone under a set of null hypotheses. Whether and how to control this issue depends on the prespecified analysis strategy. The registry record does not report a multiplicity procedure, a hierarchy among outcomes, or which comparisons were considered confirmatory.
The primary outcome itself includes repeated assessments from baseline through day 14, if applicable. The record does not identify a single time point as the principal comparison or state how the repeated measurements were incorporated into an analysis. It also does not report whether secondary outcomes were analyzed, despite listing them. The analysis count is zero, and outcome estimates are not reported in the registry record.
Missing-data handling is not reported in the registry record. The endpoint population is defined as patients still on mechanical ventilation who underwent arterial blood gas monitoring. The record does not describe how many measurements were unavailable, why they were unavailable, whether patients who left ventilation were handled differently, or whether any imputation or sensitivity analysis was used.
The analysis population is also not reported in the registry record beyond the endpoint’s stated population description. It is not clear whether results were intended to include all enrolled patients, only those receiving the intervention, or another defined group. These omissions limit assessment of the analysis’s completeness and the potential effect of missing observations.
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 |
|---|---|---|---|
| Inhaled/Nebulized Dornase Alfa | 4 | 10 | 40.0% |
| Standard of Care | 10 | 20 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Inhaled/Nebulized Dornase Alfa | 4 of 10 |
| Standard of Care | 11 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Inhaled/Nebulized Dornase Alfa | 0 of 10 |
| Standard of Care | 0 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Inhaled/Nebulized Dornase Alfa | Standard of Care |
|---|---|---|---|
| Ventilator associated pneumonia | Infections and infestations | 3 of 10 | 5 of 20 |
| Bacteremia | Infections and infestations | 1 of 10 | 3 of 20 |
| Venovenous extracorporeal membrane oxygenation | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 2 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Inhaled/Nebulized Dornase Alfa | Standard of Care |
|---|---|---|---|
| Allergic reaction to drug | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 0 of 20 |
Serious events with the highest arm-level rate: ventilator associated pneumonia (30.0%), bacteremia (15.0%), venovenous extracorporeal membrane oxygenation (10.0%).
The registry reports serious adverse event counts by arm. For inhaled or nebulized dornase alfa, 4 affected participants are recorded among 10 at risk; for standard of care, 10 affected participants are recorded among 20 at risk. Deaths are recorded as 4 in the intervention arm and 11 in the standard-of-care arm. These are descriptive registry counts, not a randomized comparison. Because allocation was non-randomized, the figures should not be read as establishing that treatment caused or prevented an event or death.
The registry records 0 other adverse events affected in each arm. It also lists ventilator associated pneumonia at 30.0%, bacteremia at 15.0%, and venovenous extracorporeal membrane oxygenation at 10.0% among the top serious adverse event terms. The denominator and time basis for these percentages are not reported in the registry record. It is also not reported whether an individual could contribute to more than one event term or how event attribution was determined.
These safety entries do not provide a complete account of timing, severity, relatedness to treatment, or differences in baseline risk. They should be understood as the registry’s recorded counts and terms, not as evidence of comparative safety.
12. What the Result Does, and Does Not, Mean
The record documents a completed study of inhaled or nebulized dornase alfa in patients with SARS-CoV-2-related ARDS, using a non-randomized parallel-arm design. It describes the intervention, the standard-of-care comparator, and a planned primary outcome based on change in PaO2/FiO2. It also lists secondary clinical outcomes and reports adverse event counts.
What the record does not provide is equally important: no primary endpoint values, confidence intervals, between-group estimates, or outcome analyses are reported. The primary measure’s direction and magnitude cannot be determined from the record. Nor can the precision of any effect estimate be assessed. The study’s completed status and recorded enrollment do not substitute for outcome data.
Even if a difference between the arms were reported, non-randomized allocation would limit causal interpretation. Groups could differ in ways that influence outcomes, and the registry does not describe the allocation process, baseline comparability, or statistical adjustment. A difference would therefore be an association in this study unless the design and analysis supported stronger interpretation; the record does not provide the information needed to assess that support.
The stated biological rationale—degrading cell-free DNA and potentially affecting mucus and neutrophil extracellular traps—is a hypothesis described in the study summary. It is not evidence that the biological mechanism changed in participants. Likewise, a planned reduction in time to recovery is not an observed result in the absence of reported outcome estimates.
The safety counts are also descriptive. Without randomized allocation and additional context about event timing, attribution, and baseline risk, they do not establish comparative risks. The appropriate reading is that the registry record identifies a clinical question and some recorded safety information, while leaving the central efficacy and statistical interpretation unresolved.
13. Why This Trial Matters Statistically
This study is statistically notable because its clinical question involves both repeated oxygenation measurements and a non-randomized comparison. Repeated measurements can describe the course of oxygenation over time, but observations from the same person are related and require an analysis that accounts for that structure. The registry specifies several assessment times but does not report the model or the resulting estimates.
The non-randomized design also changes what a comparison can establish. Randomization is one way to reduce systematic differences between groups. Here, treatment allocation was non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. This means that a statistical difference, if one were reported, would need to be considered alongside possible confounding and the method used to address it.
The primary endpoint population is defined by remaining on mechanical ventilation and undergoing arterial blood gas monitoring. This makes the availability of measurements and the handling of patients who do not meet that condition important to interpretation. The record does not report missing-data methods or the analysis population in enough detail to assess these issues.
Finally, the record illustrates a distinction between a completed trial and a reportable result. Completion and enrollment describe study status, while interpretation depends on outcome estimates, uncertainty, and analysis details. Those results are not reported in the registry record. Statistical importance therefore lies not in a conclusion about treatment, but in recognizing the design and reporting information required to evaluate the intended comparison.
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 primary limitation is that the registry record does not report primary endpoint estimates or analyses. Without observed PaO2/FiO2 means, changes, confidence intervals, or a comparison between arms, neither the size nor precision of an outcome can be assessed.
Non-randomized allocation limits the ability to interpret between-arm differences causally. The mechanism of assignment, baseline characteristics, and any adjustment for prognostic factors are not reported in the registry record. The record itself warns that the arms are not a like-for-like control comparison.
The primary endpoint population depends on remaining on mechanical ventilation and undergoing arterial blood gas monitoring. The number of observations at each assessment, reasons for unavailable measurements, and handling of missing data are not reported. It is therefore unclear how closely the analyzed measurements, if any, would represent all enrolled patients.
Single masking is recorded, but who was masked and how masking was implemented are not reported. The statistical analysis plan, treatment of repeated measures, multiplicity approach, and analysis populations are also not reported in the registry record. The record lists secondary outcomes without reporting their results.
The brief summary states a recruitment aim of 10-20 patients, while the enrollment entry is 30; no explanation is reported. Safety entries lack reported detail on event timing, attribution, and the denominators and time basis for the listed percentages. These limitations leave substantial uncertainty about both outcome interpretation and the context of the safety data.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dornase Alfa for ARDS in Patients With Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) — NCT04402970.
- Registry record last updated 2021-04-14; status last verified 2021-04.
- Results first posted 2021-04-14.
- 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
NCT04402970 is a completed Phase 3, parallel, single-masked, non-randomized study sponsored by the University of Missouri-Columbia. The registry records enrollment of 30, with a start date of 2020-06-19 and primary completion date of 2020-12-31. The brief summary states an aim to recruit 10-20 patients, and the record does not explain the difference from the enrollment entry.
The intervention was inhaled or nebulized dornase alfa at 2.5 mg twice daily for 3 days in addition to standard care. The comparator received standard care. The primary endpoint was change in PaO2/FiO2 over 14 days, assessed at baseline and specified later times if applicable.
The registry does not report the primary endpoint results or analyses. Its safety entries include serious adverse event counts and deaths, but the non-randomized design does not support a like-for-like comparison. Outcome estimates, analysis methods, and missing-data handling are not reported in the registry record.