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 ACTIV-5 / Big Effect Trial (BET-A) for the Treatment of COVID-19 (NCT04583956), a randomized phase 2 study. The primary outcome is Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04583956 |
| Phase | Phase 2 |
| Condition | COVID-19 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 214 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
Hospitalized adults diagnosed with COVID-19 were eligible for this platform trial. For the primary outcome, the registry defines the modified intention-to-treat population as randomized participants who received at least one dose of investigational product other than standard-of-care therapies, analyzed as randomized. Further eligibility details are not reported in the registry record.
Intervention
The intervention arm received remdesivir and risankizumab. The registry describes a 200-mg intravenous remdesivir loading dose on Day 1, followed by a 100-mg once-daily maintenance dose for up to a 10-day total course while hospitalized, and a 1200-mg intravenous risankizumab infusion on Day 1.
Comparator
The comparison arm received the same remdesivir regimen with a risankizumab-matched placebo infusion on Day 1. In the platform design, a control arm could be shared across interventions and could include participants receiving matched placebo for a different intervention. The extent of such sharing for this comparison is not reported in the registry record.
Primary question
Among participants in the modified intention-to-treat population, how many met the criteria for each of the eight ordinal clinical-status categories on Day 8 in each arm? The endpoint is a distribution across categories, not a single binary outcome. Category-specific results and a treatment-effect estimate for this primary outcome are not reported in the registry record.
3. Trial Design
ACTIV-5 / Big Effect Trial (BET-A) for the Treatment of COVID-19 is a Phase 2 randomized, double-blind, parallel-group component of a multicenter platform trial. The registry lists an enrollment of 214. The study was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), began on 2020-10-23, had primary completion on 2021-09-13, and is listed as completed.
The broader platform used common assessments and endpoints to evaluate putative therapeutics in hospitalized adults with COVID-19. Its stated purpose was proof of concept: identify interventions with data suggestive of efficacy that might merit a larger, more definitive study. The design description says interventions were compared with a common control and that each intervention had a matched placebo to maintain double blinding. It also describes the possibility of interventions starting at different times and of some interventions being discontinued after interim evaluations. Which interventions enrolled when, and the details or results of any interim evaluations, are not reported in the registry record.
The comparison of interest pairs remdesivir with risankizumab against remdesivir with placebo. The registry describes 100 participants for each treatment-arm description, while the safety results list 100 at risk in the risankizumab group and 107 at risk in the placebo group for the reported serious and other adverse events. These are different registry entries and should not be treated as interchangeable denominators. The reason for the difference is not reported in the registry record.
The platform description mentions up to 70 domestic sites and 5 international sites; this is a planned maximum, not a report of the number of sites that actually participated. The actual site count is not 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 | Remdesivir + Risankizumab | Remdesivir + Placebo |
|---|---|---|
| STARTED | 104 | 110 |
| Included in Modified Intention-to-treat (mITT) Population | 100 | 107 |
| COMPLETED | 83 | 85 |
| NOT COMPLETED | 21 | 25 |
Reasons for not completing this period:
| Reason | Remdesivir + Risankizumab | Remdesivir + Placebo |
|---|---|---|
| Death | 9 | 11 |
| Lost to Follow-up | 7 | 9 |
| Protocol Violation | 2 | 0 |
| Withdrawal by Subject | 0 | 2 |
| Randomized but not dosed | 2 | 3 |
| Withdrawal of consent before product administration | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized.
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: The intention-to-treat (ITT) population includes all participants who were enrolled and randomized.
| Characteristic | Unit | Remdesivir + Risankizumab | Remdesivir + Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 104 | 110 | 214 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 86 | 78 | 164 |
| Age, Categorical: >=65 years | Participants | 18 | 32 | 50 |
| Age, Continuous | years | 54.5 (SD 12.2) | 57.5 (SD 13.1) | 56.0 (SD 12.8) |
| Sex: Female, Male: Female | Participants | 36 | 52 | 88 |
| Sex: Female, Male: Male | Participants | 68 | 58 | 126 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 23 | 20 | 43 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 81 | 89 | 170 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 8 | 6 | 14 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 25 | 28 | 53 |
| Race (NIH/OMB): White | Participants | 59 | 67 | 126 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 12 | 8 | 20 |
| Region of Enrollment: United States | participants | 104 | 110 | 214 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8, measured over Day 8.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants meeting criteria for each of the eight ordinal scale categories on Day 8. The categories range from not hospitalized, through levels of hospitalization and respiratory support, to death. The category definitions distinguish both location of care and clinical support needs, including oxygen, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.
As a general statistical concept, an ordinal outcome represents ordered states: the categories have a meaningful order, but the distances between adjacent categories need not be equal. Describing the number of participants in every category can retain information about the range of clinical status rather than collapsing the scale into a simple event/no-event outcome. A category distribution can also make clear whether participants are concentrated in less severe or more severe states.
The registry identifies the primary measure as counts of participants by category at Day 8. It does not report category-specific results in the information available for this analysis, nor does it report a single summary contrast for the distribution. The primary outcome therefore cannot be reduced to a treatment-effect estimate or a claim about statistical significance.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted registry information identifies the primary endpoint and the treatment groups, but it does not give the Day 8 counts for the eight categories or an estimate comparing the groups on that endpoint. As a result, the clinical-status distribution cannot be described from the registry record, and the direction or magnitude of a primary-outcome difference cannot be assessed. The record’s stated purpose for BET was to identify promising candidates for further study, rather than to establish clear statistical significance for an intervention.
The safety entries are descriptive counts. Serious adverse events affected 24 participants among 100 at risk in the remdesivir-plus-risankizumab group and 26 among 107 at risk in the remdesivir-plus-placebo group. Other adverse events affected 24 among 100 at risk in the former group and 22 among 107 at risk in the latter. The registry lists 9 deaths for the risankizumab group and 11 for the placebo group. These counts do not establish that a treatment caused an event or that the groups differ reliably. The registry information does not supply uncertainty intervals or a comparative analysis for these figures.
As a general statistical concept, an estimate describes the observed contrast, while a confidence interval conveys the range of values compatible with the data under the analysis assumptions. Without an outcome estimate and its uncertainty, a reader cannot judge the precision of a treatment comparison. A difference in raw counts alone is not an adjusted or inferential comparison, particularly when the listed numbers at risk differ between the safety groups.
The registry lists 41 outcome measures and 7 analyses. That breadth indicates that the primary endpoint is only part of the planned or registered assessment landscape; it does not reveal how results across outcomes were prioritized or interpreted. Methods for handling multiplicity, missing observations, and the seven analyses are not reported in the registry record. The record also does not provide a primary-outcome analysis estimate in the information. Thus, the posted information supports a description of the trial structure and selected safety counts, but not a conclusion about the primary clinical-status comparison.
The listed serious adverse event terms include respiratory failure at 10.0%, acute respiratory failure at 5.6%, septic shock at 3.7%, acute myocardial infarction at 3.0%, bacterial pneumonia at 3.0%, and acute kidney injury at 2.8%. The denominator and exact population basis for these term percentages are not reported in the registry record. They should be read as registry-listed frequencies, not as comparative risks between the trial arms.
9. Statistical Methods Explained
Randomization assigns participants to treatment groups using a chance-based process. In general, this is intended to reduce systematic differences in prognostic factors between groups, although it does not guarantee identical groups. The registry identifies this study as randomized, double-blind, and parallel-group. It does not report the sequence-generation procedure, allocation-concealment details, or how blinding was maintained in practice.
What does the ordinal endpoint capture?
The primary outcome counts participants in each of eight ordered clinical-status categories at Day 8. As a general statistical concept, ordinal outcomes preserve ranking without assuming that moving between neighboring categories represents the same amount of change at every point on the scale. Reporting category counts is one way to show the distribution directly. Other possible summaries or models require explicit specification; the statistical model used for this primary outcome is not reported in the registry record.
The endpoint is a status assessment at a stated time point, rather than a time-to-event measure. It gives no information by itself about the trajectory between baseline and Day 8. The registry lists secondary outcomes that include sustained recovery, ordinal-scale assessments at Day 15 and Day 29, and changes in several laboratory measures, but their results and analysis details are not reported in the registry record.
What does the modified intention-to-treat population mean?
The primary-outcome population is defined as randomized participants who received at least one dose of investigational product other than standard-of-care therapies, analyzed according to randomized assignment. This is the registry’s stated modified intention-to-treat definition. It is not identical to a definition that necessarily includes every randomized participant, because the registry definition includes a treatment-receipt condition. The numbers included in this population for the primary outcome are not reported in the registry record.
As a general statistical concept, analyzing participants according to randomized assignment aims to preserve the comparison created by randomization. Excluding participants based on a post-randomization condition can affect that balance, depending on how exclusions relate to prognosis and treatment. The registry’s definition should therefore be read as written, without assuming that it includes all randomized participants or that particular exclusions occurred.
How should uncertainty be considered?
As a general concept, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. Wider intervals indicate less precision, while narrower intervals indicate greater precision. A p-value addresses compatibility between observed data and a specified null hypothesis under a statistical model; it does not measure clinical importance or the probability that a hypothesis is true. The registry information does not report an estimate, confidence interval, or p-value for the primary outcome, so those features cannot be evaluated for this comparison.
For count outcomes, the choice of model depends on the outcome structure and assumptions. General examples include models for binary counts, ordinal outcomes, or rates, but the appropriate approach cannot be identified solely from the endpoint label. The primary outcome consists of counts across ordered categories. The registry record does not report whether the groups were compared using a model, a global test, category-specific tests, or another procedure.
What do planning calculations represent?
As a general statistical concept, sample-size planning estimates how many participants may be needed to detect a prespecified effect with chosen error-rate and power assumptions. The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect. The calculated planning values are not reported in the registry record information available for this analysis.
Planning from an observed effect also depends on the observed estimate, which can be uncertain. A planning illustration cannot substitute for the actual treatment-effect estimate and its uncertainty. The registry does not report a sample-size justification for the trial’s original design, and the planning assumptions should not be mistaken for that justification.
How does the platform setting affect interpretation?
The registry describes a platform with a common control and matched placebos for interventions. As a general concept, shared controls can make efficient use of participants, but interpretation depends on the enrollment periods, eligibility criteria, treatment assignment, and analysis approach for each comparison. The registry says that a control could be shared and could include participants receiving placebo for another intervention. The extent and statistical handling of any shared control in this comparison are not reported in the registry record. The available description therefore does not justify assumptions about concurrent enrollment or the effect of sharing on the comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 41 outcome measures and 7 analyses. Multiple outcomes and analyses can raise multiplicity concerns because examining many estimates or tests can increase the chance of finding an apparently notable result by chance. As a general statistical concept, multiplicity can be addressed through prespecified hierarchies, adjusted thresholds, or by treating analyses as exploratory; which approach is appropriate depends on the study question and plan. The multiplicity procedure for this trial is not reported in the registry record.
The platform description states that interventions could be evaluated through interim assessments and that some could be discontinued for interim futility or efficacy. This describes the trial framework, but the timing, decision criteria, statistical adjustments, and whether any such decisions affected this comparison are not reported in the registry record. The specific interim analyses conducted for the remdesivir-plus-risankizumab comparison are not reported in the registry record.
The primary-outcome population is the modified intention-to-treat population, defined as randomized participants who received at least one dose of investigational product other than standard-of-care therapies, analyzed as randomized. The number of participants included in that analysis is not reported in the registry record. The registry information does not describe how missing Day 8 assessments were handled, whether any imputation was used, or whether sensitivity analyses assessed missing data. The amount and pattern of missing primary-outcome data are also not reported in the registry record.
These omissions matter because missingness and selective emphasis among multiple outcomes can affect interpretation. Without the analysis population counts, missing-data methods, and multiplicity plan, readers cannot determine how complete the primary assessment was or how the reported findings, if any, were protected against selective inference.
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 |
|---|---|---|---|
| Remdesivir + Risankizumab | 24 | 100 | 24.0% |
| Remdesivir + Placebo | 26 | 107 | 24.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Remdesivir + Risankizumab | 9 of 104 |
| Remdesivir + Placebo | 11 of 110 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Remdesivir + Risankizumab | 24 of 100 |
| Remdesivir + Placebo | 22 of 107 |
Most frequent serious adverse event terms
| Event term | Organ system | Remdesivir + Risankizumab | Remdesivir + Placebo |
|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 10 of 100 | 8 of 107 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 100 | 6 of 107 |
| Septic shock | Infections and infestations | 3 of 100 | 4 of 107 |
| Pneumonia bacterial | Infections and infestations | 3 of 100 | 3 of 107 |
| Acute kidney injury | Renal and urinary disorders | 2 of 100 | 3 of 107 |
| Sepsis | Infections and infestations | 2 of 100 | 2 of 107 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 2 of 100 | 2 of 107 |
| Acute myocardial infarction | Cardiac disorders | 3 of 100 | 0 of 107 |
| COVID-19 pneumonia | Infections and infestations | 2 of 100 | 1 of 107 |
| Renal Failure | Renal and urinary disorders | 1 of 100 | 2 of 107 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Remdesivir + Risankizumab | Remdesivir + Placebo |
|---|---|---|---|
| Hypertension | Vascular disorders | 4 of 100 | 10 of 107 |
| Glomerular filtration rate decreased | Investigations | 8 of 100 | 5 of 107 |
| Lymphocyte count decreased | Investigations | 6 of 100 | 6 of 107 |
| Oxygen saturation decreased | Investigations | 5 of 100 | 3 of 107 |
| Acute kidney injury | Renal and urinary disorders | 1 of 100 | 6 of 107 |
Serious events with the highest arm-level rate: respiratory failure (10.0%), acute respiratory failure (5.6%), septic shock (3.7%), acute myocardial infarction (3.0%), pneumonia bacterial (3.0%).
The registry reports serious adverse events for 24 of 100 participants at risk in the remdesivir-plus-risankizumab group and 26 of 107 at risk in the remdesivir-plus-placebo group. For other adverse events, the entries are 24 of 100 and 22 of 107, respectively. The registry lists 9 deaths in the risankizumab group and 11 in the placebo group. These are descriptive figures; they do not by themselves establish causation or a reliable difference between groups.
The listed serious adverse event terms and percentages are respiratory failure, 10.0%; acute respiratory failure, 5.6%; septic shock, 3.7%; acute myocardial infarction, 3.0%; bacterial pneumonia, 3.0%; and acute kidney injury, 2.8%. The registry information does not specify the denominator or population basis for these percentages. They should not be interpreted as arm-specific comparative rates without that information.
As a general statistical concept, adverse-event counts depend on the event definitions, observation period, and population included. The registry information does not report those details for each safety measure, nor does it report uncertainty intervals or a statistical comparison for the safety figures. The group counts therefore support a limited descriptive reading only.
12. What the Result Does, and Does Not, Mean
The registry establishes that a randomized, double-blind, parallel-group comparison was registered within a Phase 2 platform trial, and it describes the treatments and the Day 8 primary outcome. It also provides selected safety counts. Those details clarify what the trial set out to compare and what kinds of outcomes were recorded.
They do not establish the result of the primary comparison. The Day 8 counts across the ordinal categories, a treatment-effect estimate, and a measure of its uncertainty are not reported in the registry information available for this analysis. Without those results, it is not possible to describe how the groups’ clinical-status distributions differed or how precisely a difference was estimated. The trial’s stated proof-of-concept purpose also cautions against treating its design description as evidence that a larger confirmatory study was warranted or that a treatment effect was established.
The safety figures should not be treated as proof that either treatment caused or prevented an event. Raw event counts are descriptive and do not account for uncertainty, the event observation process, or any differences in the populations contributing to each measure. The term percentages have no reported denominator basis in the registry information, limiting direct interpretation.
As a general statistical concept, a study’s result is best understood through the estimate, its uncertainty, the analysis population, and the prespecified analysis plan, alongside clinical context. The registry record does not report several of these details for the primary endpoint. Consequently, the information supports a description of the design and selected safety entries, but not a conclusion about efficacy, comparative safety, or clinical importance.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of a proof-of-concept platform design. The registry describes common assessments and endpoints, a common control, and matched placebos for interventions. Such a structure is intended to support efficient screening of candidate treatments and to generate estimates that may inform the design of larger studies. The registry explicitly distinguishes that aim from establishing clear statistical significance for every intervention.
The primary endpoint also illustrates a recurring analysis choice: clinical status can be represented as an ordered set of categories rather than a single binary outcome. Category counts can retain detail about the spectrum of status, but readers need a clear analysis plan to understand how an overall comparison is made and how category-level findings are interpreted. That plan is not reported in the registry information for this comparison.
The platform context makes questions about shared controls, intervention timing, multiplicity, and interim decisions especially relevant. These are general design and analysis considerations, not evidence of a flaw in this trial. The registry describes the possibility of shared controls and interim evaluations, while the details needed to assess their statistical handling are not reported.
Finally, the record shows why design descriptions and outcome results should be distinguished. Knowing the randomization, masking, endpoint, and safety counts is useful, but it does not replace a treatment-effect estimate with its precision. Here, the primary endpoint results are not reported in the registry information available for analysis, so the trial’s statistical value cannot be judged from its design alone.
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 main limitation for interpreting the primary question is that the registry information does not report the Day 8 counts by ordinal category, an overall comparison, or an uncertainty estimate. The outcome is defined in detail, but its result cannot be reconstructed from the design description. The listed 41 outcome measures and 7 analyses also make the unreported multiplicity strategy relevant to interpretation.
The registry defines a modified intention-to-treat population for the primary outcome, but does not report its size or the number assessed at Day 8. Missing-data methods, the extent of missingness, and sensitivity analyses are not reported in the registry record. Accordingly, the completeness and robustness of the primary assessment cannot be evaluated from this information.
The treatment-arm descriptions state 100 participants for each arm, whereas the safety entries list 100 and 107 at risk. The registry information does not explain this difference. The figures should therefore be interpreted according to their specific registry labels rather than combined or treated as a single common analysis population.
For safety, the record gives group counts and selected serious-event terms, but does not report uncertainty intervals or comparative analyses. The denominator and population basis for the listed term percentages are not reported. The registry also does not provide the actual number of sites, details of enrollment timing for this comparison, or the statistical handling of any shared control. These limitations restrict interpretation to the design description and the particular descriptive safety entries reported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: ACTIV-5 / Big Effect Trial (BET-A) for the Treatment of COVID-19 — NCT04583956.
- Registry record last updated 2023-05-16; status last verified 2021-09.
- Results first posted 2022-12-19.
- 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
NCT04583956 is a completed Phase 2 randomized, double-blind, parallel-group comparison within the ACTIV-5 / Big Effect Trial platform. The registry lists enrollment of 214 and compares remdesivir plus risankizumab with remdesivir plus placebo in hospitalized adults with COVID-19.
The primary outcome is the number of participants meeting criteria for each of eight ordinal clinical-status categories on Day 8, in the modified intention-to-treat population. The category counts and a primary treatment-effect estimate are not reported in the registry information available for this analysis. Selected safety counts are reported, but they do not establish causation or comparative safety. Missing-data procedures, multiplicity methods, and details of the primary statistical analysis are not reported in the registry record.