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 BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19) (NCT04494646), a randomized phase 2 study. The primary outcome is Number of Serious Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04494646 |
| Phase | Phase 2 |
| Condition | Covid19 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 40 |
| Arms in the primary outcome | 2 |
| Lead sponsor | NYU Langone Health |
| Results posted | Yes |
2. Clinical Question
Population
BARCONA enrolled participants hospitalized with confirmed COVID-19. The registry record describes the study as a multi-center Phase II trial and lists enrollment of 40. The posted outcome reports results for the bardoxolone methyl and placebo arms; the registry record does not report further details about participant characteristics or the population used for the primary outcome.
Intervention
The intervention was bardoxolone methyl, given once daily at 20 mg according to the trial summary. Treatment was to continue for the duration of hospitalization, until recovery, with a maximum treatment duration of 29 days. The registry record does not report adherence, dose changes, or treatment actually received by each participant.
Comparator
The comparator was matching placebo. The study used randomized allocation and a 1:1 assignment plan, with permuted block randomization described in the summary. The registry record does not provide details of the randomization sequence or concealment procedures.
Primary question
The posted primary outcome is the number of serious adverse events at Day 29. The outcome reports 4 events in the bardoxolone methyl arm and 6 in the placebo arm. These are descriptive event counts, not an adjusted treatment comparison. The registry record does not report a statistical test or estimate of uncertainty for the between-arm difference, and it does not report a primary efficacy outcome.
3. Trial Design
BARCONA is recorded as a Phase II, randomized, double-blind, placebo-controlled, multi-center study. The allocation model is parallel, and masking is listed as triple. These design features are intended to make the treatment groups comparable at assignment and to reduce the influence of expectations or knowledge of assigned treatment on care and outcome assessment. The registry record does not specify who was masked or describe how masking was maintained.
The trial summary describes permuted block randomization in a 1:1 fashion. Participants were assigned to once-daily bardoxolone methyl at 20 mg or matching placebo. Treatment was planned for the duration of hospitalization, until recovery, with a maximum treatment duration of 29 days. Because treatment could end with recovery, actual treatment exposure could vary; the registry record does not report individual exposure or follow-up time.
The registry record lists enrollment of 40. The reported primary outcome has 21 participants in the bardoxolone methyl arm and 17 in the placebo arm. Those arm counts are the denominators associated with the posted outcome record; the registry record does not explain the difference between the listed enrollment and the outcome denominators. It also does not report whether any participants were excluded from the outcome analysis, or why.
The study status is completed. Its start date is 2020-09-08 and its primary completion date is 2021-01-08. The summary says the trial was designed to provide an early interim analysis of safety, but the registry record contains no posted analyses. No further details about interim monitoring, stopping rules, or the statistical design are reported in the registry record.
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 | Bardoxolone Methyl | Placebo |
|---|---|---|
| STARTED | 21 | 19 |
| COMPLETED | 21 | 17 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Bardoxolone Methyl | Placebo |
|---|---|---|
| Adverse Event | 0 | 1 |
| Withdrawal by Subject | 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.
| Characteristic | Unit | Bardoxolone Methyl | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 21 | 17 | 38 | |
| Age, Continuous | years | 57.3 (SD 16.3) | 60.5 (SD 12.5) | 57.4 (SD 14.2) |
| Sex: Female, Male: Female | Participants | 9 | 5 | 14 |
| Sex: Female, Male: Male | Participants | 12 | 12 | 24 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 5 | 6 | 11 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 16 | 11 | 27 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 3 | 4 |
| Race (NIH/OMB): White | Participants | 16 | 9 | 25 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 3 | 3 | 6 |
| Region of Enrollment: United States | participants | 21 | 17 | 38 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Serious Adverse Events, measured over Day 29.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of serious adverse events at Day 29. The registry record describes the outcome unit as adverse events and the measure as a number. The posted values are 4 for bardoxolone methyl and 6 for placebo. The record does not describe how a serious adverse event was defined, how events were collected, or how events occurring more than once in a participant were handled.
As a general statistical concept, serious adverse events are used to monitor important safety outcomes because they focus attention on events judged serious under a study’s safety definitions. A count endpoint records the number of events, rather than necessarily counting only whether each participant experienced any event. These measures answer different questions: one concerns event burden, while the other concerns the number of participants affected. The registry record does not clarify whether its primary count is a count of events, affected participants, or a particular event-counting convention beyond its stated outcome title and unit.
The endpoint is assessed at Day 29, while treatment could end earlier with recovery and was capped at 29 days. The record does not explain how participants with differing time on treatment or differing observation time contributed to the count. Therefore, the posted values should be read as the registry’s reported outcome counts, not as rates adjusted for time at risk. The listed primary endpoint addresses safety; an efficacy endpoint is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports 4 serious adverse events in the bardoxolone methyl arm and 6 in the placebo arm at Day 29. The arm denominators shown with the primary outcome are 21 and 17, respectively. These figures describe the posted results. They do not, by themselves, establish whether the observed difference is compatible with chance, whether it is clinically important, or whether it reflects a treatment effect.
No inferential analysis is posted for the primary outcome. The registry record lists no analyses and indicates that values are missing or not estimable for a two-arm comparison for this count outcome. As a result, there is no reported confidence interval, p-value, adjusted estimate, or model-based comparison to interpret. The event counts should not be treated as a statistically established difference between treatment groups.
There is also an important distinction between an event count and the proportion of participants with at least one event. If a participant can experience more than one event, the event count and the number of affected participants need not be the same. Although the adverse-event record lists serious-event counts and numbers at risk for each arm, the registry does not explain the relationship between those entries and the primary outcome’s event-counting rules. It is therefore safest to describe the primary outcome as the registry-reported number of serious adverse events, without converting it into an individual risk estimate.
The study was randomized and masked, features that can support a fair comparison when allocation, follow-up, outcome ascertainment, and analysis are handled as intended. However, a design feature does not substitute for a reported analysis. The registry record does not provide an analysis plan, details of missing outcome data, or an explanation of the analysis population. It also does not report whether outcome ascertainment differed between arms.
The registry summary describes the study as intended to examine safety, tolerability, and efficacy and to provide an early interim safety analysis. The posted outcome record contains one primary safety measure, and no efficacy result or interim analysis is reported. Accordingly, the available record supports a limited descriptive account of the serious-event counts, not a broad conclusion about safety or efficacy.
9. Statistical Methods Explained
Randomization assigns participants to study arms by a chance-based procedure. In general, this helps reduce systematic differences in prognostic characteristics between arms at assignment. BARCONA is listed as randomized, and its summary describes permuted block randomization with a 1:1 allocation plan. The registry record does not report the sequence-generation details, block sizes, allocation concealment, or whether the planned allocation was achieved in practice.
Blinding, or masking, is intended to limit the influence of knowledge about treatment assignment on participant behavior, clinical care, and outcome assessment. The registry record lists triple masking and describes the study as double-blind in its official title and summary. It does not identify which roles were masked, explain whether the placebo was indistinguishable from the active treatment, or report whether masking was assessed. The differing masking descriptions are part of the record; no further reconciliation is reported.
The primary measure is a count of serious adverse events. As a general statistical concept, count outcomes can be analyzed using methods that reflect their distribution and the amount of time participants are observed. Some count data vary more than a simple model expects, a property often called over-dispersion. In that situation, a model that allows extra variability may give more realistic uncertainty than one that assumes the count variance follows a restrictive pattern. This is general methodological context, not a description of an analysis performed in BARCONA. The registry record reports no model, test, dispersion estimate, or inferential comparison for this outcome.
Time at risk can matter for event counts. When participants have different observation periods, a raw count may combine differences in event occurrence with differences in opportunity for events to be observed. A rate-based analysis can account for person-time when appropriate, while other approaches may be suitable depending on the outcome definition and study design. BARCONA treatment could continue until recovery, with a maximum duration of 29 days, and the primary outcome is assessed at Day 29. The registry record does not report individual observation times, exposure-adjusted rates, or a method for handling different follow-up durations.
A confidence interval is a statistical range intended to express the precision of an estimated quantity under a specified method and assumptions. A narrow interval generally indicates greater precision than a wide interval, while an interval that includes values on both sides of a null comparison can indicate that the data do not clearly distinguish those possibilities under that method. This is general explanation. No confidence interval or comparable uncertainty estimate is reported for the primary outcome, so the precision of a treatment comparison cannot be assessed from the registry record.
A p-value, when reported, describes how unusual data at least as incompatible with a specified null model would be if that model and the test assumptions held. It is not the probability that a treatment is effective, nor a measure of clinical importance. No p-value is reported for the primary outcome. The registry record also does not identify a prespecified hypothesis test or state whether any adjustment was planned for multiple outcomes or analyses.
Because the endpoint is a count, a raw difference in counts would not necessarily be an adequate treatment-effect estimate, particularly if the groups differ in observation time or if participants can contribute multiple events. Suitable analysis choices depend on the endpoint’s precise definition, the distribution of counts, follow-up, and the intended estimand. These details are not reported in the registry record. The registry explicitly indicates that values are missing or not estimable for a two-arm comparison for this count outcome, so no recalculated comparison should be substituted for the sponsor’s own analysis. No sponsor analysis is posted in the record.
For planning a future study, power calculations require assumptions about the effect to detect, variability, allocation, significance level, and analysis method. A planning illustration based on an observed effect is not evidence that the completed trial had a particular power. The registry record does not report the trial’s sample-size justification, target power, or assumptions used in its design. Its enrollment figure and observed outcome counts cannot on their own establish whether the study was adequately powered to detect a safety or efficacy difference.
In general, a transparent report of a randomized comparison would identify the analysis population, the number of participants contributing to each endpoint, the handling of missing data, the statistical model, and an effect estimate with uncertainty. This information helps readers distinguish the observed data from assumptions introduced by an analysis. The registry record does not report those analysis details for the primary outcome, which limits statistical interpretation to a description of the posted counts.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, comparisons, time points, or analyses are tested. In general, the more opportunities there are to find an apparently notable result, the greater the chance that at least one result may appear unusual by chance alone. Statistical plans may address this issue by identifying a primary comparison in advance or by adjusting inference across a family of tests. The registry lists one outcome measure and no posted analyses. Whether other outcomes or analyses were planned, and whether multiplicity procedures were specified, is not reported in the registry record.
The registry summary says the study was designed to provide an early interim analysis of safety. The record does not report an interim analysis, its timing, any decision rules, or whether interim findings affected the final analysis. The completed status alone does not establish that an interim analysis was conducted or how it was handled.
Missing-data handling is also not described. The primary outcome has arm denominators of 21 and 17, while listed enrollment is 40. The registry record does not explain the difference, identify any missing endpoint observations, or state how participants without an observed outcome were treated. It does not report an analysis population such as all randomized participants or participants with available outcome data.
These omissions matter because exclusions or incomplete follow-up can affect which participants are represented in an outcome summary. Without a reported accounting of participant flow and missingness, readers cannot determine whether the posted counts reflect all randomized participants or a subset. No imputation, sensitivity analysis, or other missing-data method is reported in the registry record.
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 |
|---|---|---|---|
| Bardoxolone Methyl | 4 | 21 | 19.0% |
| Placebo | 6 | 17 | 35.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Bardoxolone Methyl | 0 of 21 |
| Placebo | 4 of 17 |
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 |
|---|---|
| Bardoxolone Methyl | 1 of 21 |
| Placebo | 1 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Bardoxolone Methyl | Placebo |
|---|---|---|---|
| Presyncope, Pre-syncope | Nervous system disorders | 0 of 21 | 1 of 17 |
| Hypoxia, Worsening hypoxia | Respiratory, thoracic and mediastinal disorders | 0 of 21 | 1 of 17 |
| Cardiac failure acute, Acute on chronic systolic (congestive) heart failure | Cardiac disorders | 0 of 21 | 1 of 17 |
| Nephrolithiasis, Nephrolithiasis | Renal and urinary disorders | 1 of 21 | 0 of 17 |
| Splenic rupture | Injury, poisoning and procedural complications | 1 of 21 | 0 of 17 |
| Mechanical ventilation, Invasive mechanical ventilation | Surgical and medical procedures | 1 of 21 | 0 of 17 |
| Abdominal wall wound, Worsening abdominal wound | Injury, poisoning and procedural complications | 1 of 21 | 0 of 17 |
| Respiratory failure Worsening hypoxemic respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 21 | 1 of 17 |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | 0 of 21 | 1 of 17 |
| Mechanical ventilation | Surgical and medical procedures | 0 of 21 | 1 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bardoxolone Methyl | Placebo |
|---|---|---|---|
| Dizziness and Lightheadedness | Nervous system disorders | 1 of 21 | 0 of 17 |
| Fungal Infection | Infections and infestations | 0 of 21 | 1 of 17 |
| Loss of Consciousness | Nervous system disorders | 1 of 21 | 0 of 17 |
| Blackouts | Nervous system disorders | 1 of 21 | 0 of 17 |
Serious events with the highest arm-level rate: presyncope, pre-syncope (5.9%), hypoxia, worsening hypoxia (5.9%), cardiac failure acute, acute on chronic systolic (congestive) heart failure (5.9%), respiratory failure worsening hypoxemic respiratory failure (5.9%), pulmonary embolism (5.9%).
The primary outcome reports 4 serious adverse events in the bardoxolone methyl arm and 6 in the placebo arm at Day 29. The registry’s adverse-event record lists 4 serious events among 21 at risk for bardoxolone methyl and 6 among 17 at risk for placebo. It also records deaths as 0 in the bardoxolone methyl group and 4 in the placebo group. These are descriptive registry entries, not adjusted comparisons.
The record does not define whether each serious-event count represents events, participants affected, or another counting convention, and it does not report a statistical comparison. The numbers should therefore not be read as evidence that one treatment caused more or fewer events. The death counts are also descriptive; the registry does not report their timing, causes, adjudication, or a formal analysis.
The serious-event terms listed in the record include presyncope, hypoxia or worsening hypoxia, acute cardiac failure, worsening hypoxemic respiratory failure, pulmonary embolism, and mechanical ventilation. Each listed term is paired with 5.9% in the registry. The record does not provide enough detail to establish how those terms map to the primary event count or whether categories overlap. These figures should be interpreted as reported event-term entries, not as a complete safety profile or a causal assessment.
As general guidance for reading safety summaries, distinguish event counts from the number of participants affected, note the observation period, and check whether follow-up time and event definitions are comparable. Those details are not fully reported for this outcome.
12. What the Result Does, and Does Not, Mean
The posted result establishes that the registry records 4 serious adverse events for bardoxolone methyl and 6 for placebo at Day 29. It also shows the denominators attached to the outcome record: 21 in the bardoxolone methyl arm and 17 in the placebo arm. These are descriptive findings from the registry record, not a complete estimate of comparative safety.
The result does not establish that the treatments differ. No statistical comparison, confidence interval, or p-value is posted, and the registry states that values are missing or not estimable for a two-arm comparison of this count outcome. The counts alone do not indicate how much uncertainty surrounds a comparison or whether an observed difference is likely to reflect chance variation.
The result also does not establish that either treatment is safe or unsafe, or that either treatment changes the risk of serious adverse events. The endpoint’s counting rules are not described in detail, and the record does not report participant-level event status, person-time, missing-data handling, or an adjusted analysis. The death counts and serious-event terms are descriptive entries and do not establish causation.
The registry summary mentions safety, tolerability, and efficacy as study aims, but the posted primary outcome is a safety count. No efficacy result is reported in the registry record. The observed counts should not be extended to outcomes, populations, or follow-up beyond those recorded.
In general, randomized and masked designs can support treatment comparisons, but conclusions depend on complete outcome reporting and an analysis suited to the endpoint. For this record, the defensible interpretation is narrow: it documents the reported serious-event counts and leaves the comparative effect and its precision unresolved.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its primary outcome is an event count, while the registry does not provide a comparative analysis. A count is not automatically equivalent to the number of participants affected, and interpretation can depend on event definitions, repeated events, and time under observation. The record’s treatment period could vary with recovery, making information about follow-up and exposure relevant to an event-count comparison.
The trial also illustrates the difference between a randomized design and a reported treatment-effect estimate. Random allocation and masking are important design features, but readers still need an analysis that connects the observed outcomes to a defined comparison and quantifies uncertainty. In this case, the record supplies descriptive counts but no inferential estimate for the primary outcome.
The summary describes an intended early interim safety analysis, but the completed record does not post such an analysis or explain any interim procedures. This distinction is important: an intention described in a study summary is not itself evidence that an analysis was conducted or that its results are available.
Finally, the difference between the listed enrollment and the arm denominators accompanying the primary outcome highlights why participant flow and analysis populations matter. Without an explanation of who contributed to the endpoint, readers cannot fully assess the relationship between enrollment and the reported results. BARCONA therefore offers a useful example of how registry results can document outcomes while leaving key elements of statistical interpretation unreported.
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 record constrain interpretation. The registry lists enrollment of 40, but the primary outcome is accompanied by arm denominators of 21 and 17. The reason for this difference is not reported in the registry record. Participant flow, exclusions, and the analysis population are also not reported, so it is not possible to determine how the outcome denominators were formed.
The primary endpoint is identified as the number of serious adverse events at Day 29, but its operational definition and event-counting rules are not reported. The record does not clarify whether repeated events in one participant contribute separately, how events were adjudicated, or how events were linked to the other safety entries. This limits interpretation of the counts and their relationship to the number of participants affected.
Treatment was planned until recovery, with a maximum duration of 29 days. The registry does not report individual treatment exposure, time at risk, or whether all participants had comparable observation. The posted outcome is not presented as a rate adjusted for follow-up time.
No statistical analysis, confidence interval, p-value, missing-data method, or sensitivity analysis is posted. The trial’s sample-size justification and statistical plan are not reported in the registry record. The summary mentions an early interim safety analysis, but no interim results or procedures are reported. The record also does not post an efficacy outcome. These limitations prevent a broader or more precise comparative interpretation of the completed trial.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19) — NCT04494646.
- Registry record last updated 2022-01-13; status last verified 2022-01.
- Results first posted 2022-01-12.
- 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
BARCONA (NCT04494646) is a completed Phase II randomized, double-blind, placebo-controlled, multi-center study of bardoxolone methyl in participants hospitalized with confirmed COVID-19. The registry lists triple masking and a parallel allocation model. The study summary describes once-daily bardoxolone methyl at 20 mg versus matching placebo, assigned in a 1:1 fashion, with treatment through recovery and a maximum duration of 29 days.
Enrollment is listed as 40. The primary outcome is the number of serious adverse events at Day 29, with 4 reported for bardoxolone methyl and 6 for placebo. The associated outcome denominators are 21 and 17. The registry record posts no statistical analyses and indicates that a two-arm comparison for this count outcome is missing or not estimable. It does not report an efficacy result, analysis plan, or explanation of the outcome denominators.