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 A Trial of GC4419 in Patients With Critical Illness Due to COVID-19 (NCT04555096), a randomized phase 2 study. The primary outcome is 28 Day All-cause Mortality.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04555096 |
| Phase | Phase 2 |
| Condition | Covid19, SARS-CoV-2 Infection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Galera Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
The trial asked whether GC4419, also named avasopasem manganese in the official title, could be evaluated against placebo in patients with critical illness due to SARS-CoV-2 infection (COVID-19). The primary outcome was all-cause mortality 28 days after initiation of therapy. The registry record identifies a randomized, parallel-group comparison and describes the study as a pilot trial. It does not provide a numerical result for the primary outcome or an analysis comparing the arms, so the clinical question is visible but its answer is not available from the posted results.
Population
Patients with critical illness due to COVID-19, as described in the trial title and primary endpoint description. Specific eligibility criteria, clinical characteristics, and the definition of critical illness are not reported in the registry record.
Intervention
GC4419, identified in the official title as avasopasem manganese. The posted record does not describe the dose, route, or schedule in the registry record.
Comparator
Placebo. The record describes the study as placebo-controlled, but does not report further details about placebo administration or how treatment was delivered.
Primary question
What was the count of participants who died from any cause within 28 days after therapy initiation in each arm, and how did the arms compare? The registry record identifies this endpoint but does not report an arm-level primary result or comparison.
This framing separates the intended question from the evidence posted in the record. Randomization describes the planned allocation approach; it does not itself establish the outcome. Likewise, the endpoint description does not show how many participants experienced it. The analysis therefore has to focus on what can be read from the design and safety entries, while treating the primary mortality result as unavailable in the registry record.
3. Trial Design
The registry describes a phase 2, randomized, placebo-controlled, parallel-group pilot trial. The listed interventions are GC4419 and placebo, with the arms identified as Active GC4419 and Placebo. Enrollment is recorded as 16. The record says the trial was terminated; it does not state the reason for termination in the registry record. The recorded start date is 2020-09-09, and the primary completion date is 2021-05-28.
Randomization is intended to allocate participants by chance rather than by clinical choice. In general, that approach can reduce systematic differences between groups at the time of allocation, although it cannot guarantee that groups will be similar in a small trial. The posted at-risk counts in the serious-adverse-event entries are 9 for Active GC4419 and 7 for Placebo. Those figures describe the safety entries and should not be treated as a complete account of the allocation process or as a substitute for a participant flow diagram. Further details about screening, exclusions, withdrawals, and the numbers included in each analysis are not reported in the registry record.
The record marks masking as quadruple. This indicates the registry’s masking classification, but the identities of the parties who were masked and the practical masking procedures are not reported in the registry record. The record also gives no dosing, treatment-duration, or adherence information in the registry record. The official title calls the study a pilot; that label does not tell us the protocol’s sample-size justification or the precision the investigators intended to achieve. Those details are not reported in the registry record.
The available design information establishes the broad comparison and trial status, but does not provide enough detail to reconstruct the protocol or participant experience. No more specific design feature should be inferred from the trial title or from the posted adverse-event counts.
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 | Active GC4419 | Placebo |
|---|---|---|
| STARTED | 9 | 7 |
| COMPLETED | 4 | 2 |
| NOT COMPLETED | 5 | 5 |
Reasons for not completing this period:
| Reason | Active GC4419 | Placebo |
|---|---|---|
| Death | 4 | 4 |
| Withdrawal by Subject | 1 | 0 |
| Other | 0 | 1 |
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.
Population: Baseline analysis population is the same.
| Characteristic | Unit | Active GC4419 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 7 | 16 | |
| Age, Continuous | years | 62.7 (SD 6.89) | 64.0 (SD 11.28) | 63.3 (SD 61.5) |
| Sex: Female, Male: Female | Participants | 1 | 3 | 4 |
| Sex: Female, Male: Male | Participants | 8 | 4 | 12 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 0 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 7 | 7 | 14 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): White | Participants | 5 | 5 | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 1 | 3 |
| Region of Enrollment: United States | participants | 9 | 7 | 16 |
6. Primary Endpoint
The registry lists the primary outcome as 28 Day All-cause Mortality, measured over 28 days.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “28 Day All-cause Mortality.” It measures the count of participants who died from any cause during the 28 days after initiation of therapy. Because it is all-cause mortality, the endpoint concerns death regardless of the recorded cause; it is not limited to deaths attributed to COVID-19 or to the study treatment. The registry describes the unit as participants and the measure as a count.
In general, mortality is used as an outcome because it is a clearly defined event and does not depend on a subjective assessment of symptom change. A fixed follow-up window also specifies the period in which events are counted. These general features do not establish why this particular endpoint was selected; the endpoint-selection rationale is not reported in the registry record.
The endpoint description is not itself a result. The record does not give the number of deaths in either arm for this primary measure, a between-arm estimate, or uncertainty around a comparison. The primary endpoint has several categories or time points in the posted outcome structure and is not reduced to one comparison. For that reason, the page should not interpret a count from the separate safety listing as the primary mortality result, even though the safety listing also includes deaths. The endpoint and the available safety data serve different roles in the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry identifies a primary mortality question but does not post a result that answers it. The listed endpoint is all-cause mortality 28 days after therapy initiation. However, the outcome entry is not reduced to a single comparison, and the record reports no primary analysis. There is therefore no posted arm-level estimate, uncertainty interval, or statistical test for the primary endpoint to interpret. The page cannot determine from this record whether the observed mortality differed between GC4419 and placebo, or how precisely any difference was estimated.
The study was recorded as terminated and enrolled 16 participants. These registry entries matter for context, but neither explains the termination nor establishes why the primary analysis is absent. The reason for termination, the sample-size justification, and the analysis plan are not reported in the registry record. It would be speculative to attribute the missing comparison to any particular operational or statistical reason.
The posted safety entries show serious adverse events affecting 5 of 9 participants at risk in Active GC4419 and 4 of 7 in Placebo. Other adverse events are recorded for 8 of 9 and 7 of 7 participants, respectively. Deaths are listed for 4 participants in each group in those safety entries. These counts describe the safety data as posted; they are not the primary endpoint analysis and do not show whether deaths occurred within the primary endpoint’s 28-day window. The registry record does not provide enough detail to equate the safety death counts with the primary endpoint counts.
In general, an estimate is more informative when accompanied by an uncertainty interval, which indicates a range of values compatible with the data under the analysis assumptions. A statistical test alone would not describe the size or precision of an effect. Neither an estimate nor an interval for the primary comparison is reported in the registry record, so statistical significance and precision cannot be assessed from this entry.
The study’s pilot designation and small enrollment make caution appropriate, but they do not justify a claim about benefit, harm, or equivalence. The posted evidence permits description of the design and listed safety counts. It does not support a conclusion about the primary mortality comparison.
9. Statistical Methods Explained
The registry identifies a binary primary outcome measured as a count of participants: death from any cause by 28 days after initiation of therapy. A binary outcome records whether each participant experienced the event within the defined period. In general, such data can be summarized as event counts and the number of participants assessed in each arm, then compared using a method suited to the design and the analysis plan. The registry record does not report which statistical method was planned or used for the primary endpoint.
What can the design tell us?
Random allocation and parallel groups define the basic comparison: participants are assigned to one of the two intervention arms and outcomes are considered across those groups. In general, randomization can support causal interpretation when allocation is implemented as planned and the analysis preserves the randomized comparison. It does not remove uncertainty, and it does not guarantee balance in every baseline characteristic. The record does not provide enough information to assess allocation concealment, baseline balance, treatment adherence, or departures from the assigned intervention.
Masking is listed as quadruple, but the registry record does not identify which individuals were masked or describe how masking was maintained. Those details can matter for outcomes that involve judgment or for decisions about care and follow-up. Mortality itself is a comparatively objective event, but the endpoint’s ascertainment and follow-up procedures are not reported in the registry record.
Why is there no primary comparison to interpret?
The posted outcome structure is not reduced to one comparison because the primary outcome has several categories or time points. The registry also records no analyses. Accordingly, there is no reported estimate, test statistic, confidence interval, or p-value for the primary comparison in the registry record. This absence should not be filled by calculating an effect from the safety entries: those entries are not identified as the primary outcome analysis and do not establish the specified 28-day time window.
In general, a confidence interval communicates statistical uncertainty around an estimate. A narrow interval indicates greater precision under the model and assumptions used; a wide interval indicates less precision. A p-value summarizes how compatible the observed data are with a specified null model, given the method’s assumptions. Neither quantity gives the probability that a treatment works, and neither substitutes for considering the size and clinical meaning of an effect. Since the registry record posts no primary estimate or inferential result, those interpretive tools cannot be applied to the primary comparison.
How should planning illustrations be read?
The sample-size section contains planning illustrations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. These are assumptions for the illustration, not a report of the trial’s original design rationale. The registry record does not report the protocol’s sample-size justification. The illustrations should not be read as evidence that the trial had a particular probability of detecting an effect, nor as a substitute for an analysis of the participants’ outcomes.
More generally, a planning calculation asks how much information might be needed to detect an effect under specified assumptions. Its output depends on the effect selected and the statistical model. When the primary result is not available as a single comparison, a planning illustration cannot resolve the missing outcome evidence. The values in the calculated sample-size section are separate from the posted trial results and should be interpreted only according to their stated assumptions.
Why can over-dispersion matter?
General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It can make standard errors too small if the model fails to account for that extra variability, which can in turn make intervals too narrow and tests too optimistic. This concept is relevant to some count-data models, but the primary outcome is described as a participant count for a binary event. The registry does not report a model or an over-dispersion assessment for this trial, so it would be inappropriate to claim that over-dispersion was present or was addressed.
The trial enrollment and the safety at-risk counts give context for the posted data, but they do not establish which participants were included in the primary analysis. Analysis populations, missing-outcome handling, and methods for participants with incomplete follow-up are not reported in the registry record. Any method-specific interpretation beyond the broad outcome definition would therefore be speculation.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan, a strategy for controlling multiplicity, or a hierarchy of primary and secondary hypotheses. The primary outcome entry is not reduced to one comparison because it has several categories or time points. Without a reported analysis plan, it is not possible to determine how the investigators intended to handle multiple comparisons or which specific contrast would have been treated as primary. No adjustment method should be inferred.
Missing-data procedures are also not reported in the registry record. The available information does not explain whether all participants completed the 28-day follow-up, how incomplete outcome status was handled, or whether any imputation or sensitivity analysis was planned. In general, missing outcome data can affect an analysis if the probability of missingness is related to participant outcomes or treatment assignment. That general concern does not establish that missing data occurred in this trial.
The analysis populations are not reported in the registry record. The record does not identify whether the primary outcome analysis was intended to include all randomized participants, participants who received study treatment, or another defined group. The safety entries’ at-risk counts should not be assumed to define the primary analysis population. With no reported analysis and no stated missing-data or multiplicity approach, the robustness of a primary result cannot be assessed from the registry entry.
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 |
|---|---|---|---|
| Active GC4419 | 5 | 9 | 55.6% |
| Placebo | 4 | 7 | 57.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Active GC4419 | 4 of 9 |
| Placebo | 4 of 7 |
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 |
|---|---|
| Active GC4419 | 8 of 9 |
| Placebo | 7 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Active GC4419 | Placebo |
|---|---|---|---|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 9 | 2 of 7 |
| Cardiogenic Shock | Cardiac disorders | 1 of 9 | 0 of 7 |
| Stress cardiomyopathy | Cardiac disorders | 1 of 9 | 0 of 7 |
| Retroperitoneal haematoma | Gastrointestinal disorders | 1 of 9 | 0 of 7 |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 1 of 7 |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 1 of 7 |
| Respiratory arrest | Respiratory, thoracic and mediastinal disorders | 1 of 9 | 0 of 7 |
| Increased respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 1 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Active GC4419 | Placebo |
|---|---|---|---|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 3 of 9 | 3 of 7 |
| Hypotension | General disorders | 5 of 9 | 1 of 7 |
| Pyrexia | General disorders | 3 of 9 | 2 of 7 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 9 | 2 of 7 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 9 | 2 of 7 |
| Hypophosphataemia | Metabolism and nutrition disorders | 3 of 9 | 0 of 7 |
| Constipation | Gastrointestinal disorders | 1 of 9 | 1 of 7 |
| Hyperkalaemia | Metabolism and nutrition disorders | 2 of 9 | 0 of 7 |
| Hyperphosphataemia | Metabolism and nutrition disorders | 2 of 9 | 0 of 7 |
| Malnutrition | Metabolism and nutrition disorders | 1 of 9 | 1 of 7 |
Serious events with the highest arm-level rate: acute respiratory failure (28.6%), acute respiratory distress syndrome (14.3%), pneumothorax spontaneous (14.3%), increased respiratory failure (14.3%), cardiogenic shock (11.1%).
The registry lists serious adverse events for Active GC4419 and Placebo. In the Active GC4419 group, 5 of 9 participants at risk were recorded as affected by a serious adverse event; in the Placebo group, 4 of 7 were recorded as affected. The entries for other adverse events show 8 of 9 affected in Active GC4419 and 7 of 7 in Placebo. The registry also lists deaths for 4 participants in each group.
These are descriptive safety figures. They do not establish that an event was caused by study treatment, and the record does not provide the event-level timing or attribution needed to make that judgment. The listed deaths are in the safety entries; they should not be treated as the primary 28-day all-cause mortality result because the registry does not link them to that endpoint’s time window or report the primary comparison.
The registry lists the following serious adverse event terms and percentages: Acute respiratory failure, 28.6%; Acute respiratory distress syndrome, 14.3%; Pneumothorax spontaneous, 14.3%; Increased respiratory failure, 14.3%; Cardiogenic Shock, 11.1%; and Stress cardiomyopathy, 11.1%. These terms are presented as posted and are not assigned to a particular arm in the information. The registry record does not report further details about event severity grading, duration, relatedness, or overlap between participants and event terms. The counts and percentages should therefore be read as a summary of recorded safety events, not as a causal comparison.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, placebo-controlled phase 2 pilot trial of GC4419 in critical illness due to COVID-19 was conducted, with a primary endpoint of 28-day all-cause mortality. It also records that the trial was terminated, had enrollment of 16, and includes arm-specific safety entries. These registry entries describe the study and the data posted in the registry; they do not answer the primary clinical question.
The primary outcome result is not reported as a single comparison, and the record contains no analysis. There is no posted estimate of the difference between arms, no interval describing uncertainty, and no reported statistical test for the primary endpoint. Consequently, this entry cannot support a claim that GC4419 reduced mortality, increased mortality, or had no effect. Absence of a reported comparison is not evidence of equivalence.
The safety entries can be described as counts of participants with recorded serious and other adverse events, along with death counts. They do not, by themselves, establish causation or provide a complete benefit-harm assessment. The registry record does not report whether the listed deaths occurred during the primary endpoint window, nor does it provide event attribution in the registry record. The serious-event terms and percentages are also not sufficient to establish an arm-level comparison.
In general, the strength of an interpretation depends on the quality and completeness of the reported outcome data, the analysis methods, and the precision of the estimates. Here, key elements—including the primary analysis, analysis populations, missing-data approach, and statistical plan—are not reported in the registry record. The appropriate conclusion is limited: the record documents the design and selected safety information, while leaving the primary mortality result unresolved.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry entry presents a clear clinical endpoint but does not provide a single primary comparison to interpret. That distinction is important in clinical research: an endpoint definition tells readers what the study intended to measure, whereas a result requires observed outcome data and an analysis. A registered question is not an answer.
The pilot designation and enrollment of 16 also make precision a central consideration. In general, estimates from small studies can be uncertain, and a lack of a statistically significant result—if one were reported—would not by itself establish that groups were equivalent. In this record, however, even that question cannot be assessed because the primary estimate and its uncertainty are not reported. The caution comes from the limits of the posted information, not from an assumed outcome.
The calculated tables, plots, and planning section can help readers understand the posted data and statistical concepts, but they should not be confused with a sponsor-reported primary analysis. Planning illustrations rely on stated assumptions and are not observed power. Likewise, the adverse-event counts are safety summaries rather than substitutes for the 28-day mortality endpoint.
For biostatisticians and clinical researchers, the record illustrates why interpretation depends on reporting as well as design. Randomization and masking are useful design features, but they do not supply missing estimates, confidence intervals, analysis populations, or details on missing outcomes. The terminated status and absence of a posted primary analysis are therefore essential context. The trial matters statistically as an example of the boundary between what a registry entry documents and what readers can responsibly infer from it.
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 trial-specific limitations constrain interpretation of this registry entry. The study is recorded as terminated, but the reason for termination is not reported in the registry record. The record gives enrollment of 16 and at-risk counts in the safety entries, but does not provide a participant flow account showing screening, allocation, follow-up, withdrawals, or the analysis population for the primary outcome.
The 28-day all-cause mortality endpoint is specified, but the posted outcome is not reduced to one comparison and no analysis is recorded. There is no primary arm-level result, uncertainty interval, or statistical test to interpret. The registry entries do not establish whether the primary outcome was collected for every participant or whether any data were missing. Missing-data handling, analysis populations, and sensitivity analyses are not reported in the registry record.
The record identifies randomization, parallel groups, placebo control, and quadruple masking, but does not give allocation procedures or identify who was masked. It also does not report treatment dose or schedule, participant characteristics, baseline comparability, adherence, or details of outcome ascertainment. These omissions limit assessment of how the planned design was implemented.
The safety entries are informative as posted counts, but provide no event timing or treatment-relatedness information in the registry record. The death counts in those entries cannot be assumed to be the primary endpoint counts within the specified follow-up window. The sample-size justification and statistical analysis plan are not reported in the registry record, so the rationale for enrollment and intended inferential approach cannot be reconstructed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Trial of GC4419 in Patients With Critical Illness Due to COVID-19 — NCT04555096.
- Registry record last updated 2022-03-18; status last verified 2022-03.
- Results first posted 2022-03-18.
- 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 phase 2, randomized, placebo-controlled, parallel-group pilot trial of GC4419 versus placebo in patients with critical illness due to COVID-19. Enrollment is recorded as 16, masking as quadruple, and study status as terminated. The listed dates are start on 2020-09-09 and primary completion on 2021-05-28.
The primary endpoint is 28-day all-cause mortality, measured as a participant count. The posted outcome is not reduced to one comparison, and no primary analysis is reported. Safety entries list serious adverse events, other adverse events, and deaths by arm; these entries do not replace the primary endpoint analysis or establish event causation. The reason for termination, analysis populations, missing-data methods, sample-size justification, and statistical plan are not reported in the registry record.