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 Non-comparative Trial of the Combination of HCQ and AZI in the Treatment of ICU Patients (NCT04458948), a na phase 2 study. The primary outcome is Number of Participants That Had Viral Shedding as Determined by RT-PCR..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04458948 |
| Phase | Phase 2 |
| Condition | COVID-19 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of New Mexico |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes hospitalized patients with moderate or severe COVID-19 infection. The primary-outcome population is described as 28 patients with COVID-19 pneumonia. The trial title refers to ICU patients, while the official title and outcome description refer more broadly to hospitalized patients; the record does not clarify the precise relationship between these descriptions.
Intervention
All subjects in the single group received hydroxychloroquine and azithromycin. The record identifies both as drug interventions and describes the trial as open label. It does not report a separate intervention group receiving either drug alone.
Comparator
There was no comparator group in this non-comparative, single-group trial. The record therefore does not provide a randomized, concurrent contrast with usual care, placebo, or another treatment. Observed outcomes describe participants in the treated group and cannot, by themselves, separate treatment effects from other influences on outcomes.
Primary question
The primary outcome is the number of participants with viral shedding as determined by RT-PCR, with a timeframe stated as 14 to 28 days. Its description says the trial aimed to measure the duration of viral shedding in respiratory secretions among patients with moderate to severe COVID-19 who received the combination. The actual endpoint result is not reported in the registry record.
3. Trial Design
This was an open-label, non-comparative prospective trial, listed as Phase 2. Its model was single group, and allocation was recorded as not applicable. The registry status is terminated. The sponsor was the University of New Mexico. The record gives a start date of 2020-03-24 and a primary completion date of 2020-08-28.
The intervention group was named “Hydroxychloroquine and Azithromycin,” and its description states that all subjects received both drugs. With no control arm, the trial was structured to describe outcomes within the treated group rather than estimate a randomized between-group difference. “Open label” means the study was not masked; the record lists masking as none.
The record lists enrollment as 28 and describes the primary-outcome population as 28 patients with COVID-19 pneumonia. It records one outcome measure and no analyses. The registry material does not report the actual primary-outcome count, an effect estimate, or a statistical comparison. The reasons for termination, the planned enrollment target, and whether enrollment was completed as planned are not reported in the registry record.
The title mentions ICU patients, whereas the official title describes hospitalized patients with moderate or severe COVID-19. The outcome description likewise refers to moderate to severe infection. The registry record does not reconcile these differences, so the precise clinical setting and eligibility boundaries should not be inferred beyond those descriptions.
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 | Hydroxychloroquine and Azithromycin |
|---|---|
| STARTED | 28 |
| COMPLETED | 0 |
| NOT COMPLETED | 28 |
Analysis population for the primary outcome, as defined in the registry: 28 patients all had COVID -19 pneumonia.
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: Our baseline population is from the state of New Mexico, Navajo nation and other surrounding Pueblo nations. We enrolled 28 patients, about equal males and females, ages from 32 to 85.
| Characteristic | Unit | ICU Patients in Our Quarterary Care |
|---|---|---|
| Participants analysed | 28 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 |
| Age, Categorical: >=65 years | Participants | 19 |
| Age, Continuous | years | 70 (32 to 85) |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 18 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: United States | Participants | 28 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants That Had Viral Shedding as Determined by RT-PCR., measured over 14 to 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 “Number of Participants That Had Viral Shedding as Determined by RT-PCR.” It is a count of participants with the event, and the registry specifies participants as the unit. The stated timeframe is 14 to 28 days. The endpoint description frames the objective as measuring the duration of viral shedding in respiratory secretions among patients with moderate to severe COVID-19 treated with hydroxychloroquine and azithromycin.
RT-PCR is the stated method for determining viral shedding. In general, a laboratory-defined endpoint can make an outcome more operationally specific than a broad clinical description, because it ties the event to a named measurement method. Interpretation still depends on the collection schedule, specimen handling, positivity criteria, and rules for determining when shedding ends. Those details are not reported in the registry record.
The title describes a participant count, while the objective refers to duration. These are related but not identical ways to summarize an outcome: a count indicates how many participants met a definition, whereas duration concerns how long an event persists. The registry does not report the observed count, a duration estimate, or the detailed analysis used to connect the stated objective with the listed endpoint. The endpoint result is not reported in the registry record, so no conclusion about the observed pattern of viral shedding can be drawn from this entry.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical constraint is the absence of a reported primary-outcome result. Although the registry names a viral-shedding endpoint and gives its measurement method and timeframe, it does not state how many participants had viral shedding or report a duration estimate. Consequently, there is no posted primary estimate to describe, no uncertainty interval to assess, and no basis in the registry record for judging the precision of the endpoint result.
The single-group, non-comparative design also limits what any within-group result could establish. A count of participants with viral shedding would describe observations among people who received the combination. Without a concurrent comparator, it would not show how those observations differed from what would have occurred under another treatment or without the combination. Differences in participants, disease course, clinical care, or measurement timing could also affect observed outcomes. These are general interpretive considerations, not findings about this trial.
The registry reports that 9 participants were affected by serious adverse events among 28 at risk, and that no participants were affected by other adverse events among 28 at risk. It also reports a serious-event term, “Clotting to vital organs (lungs, heart, kidney and brain),” with 32.1%. The record does not provide further detail in these entries about event timing, recurrence, severity grading, or how the percentage for the term was calculated. The serious-event count and the term percentage should therefore be read as registry entries, not as a full clinical characterization or a comparison with another group.
The registry also lists deaths as 28. This entry is striking alongside the other safety counts, but the record as summarized does not explain its meaning or provide narrative context. It should be reported as recorded and treated as requiring verification; it should not be silently changed or assumed to mean something different. The entry alone does not clarify timing, cause, or relationship to treatment.
Overall, the available record supports a description of the planned question, single-group design, and selected safety entries. It does not support an estimate of comparative effectiveness, a causal treatment claim, or a precise account of the primary endpoint. A lack of a reported endpoint result is not evidence that the endpoint was absent or that a particular result occurred.
9. Statistical Methods Explained
What does a single-group design estimate?
In general, a single-group study describes outcomes observed among participants who receive the intervention. It can characterize what happened in that group, but it does not directly estimate a treatment contrast against a concurrent control group. Here, the registry identifies a single group receiving hydroxychloroquine and azithromycin and labels the trial non-comparative. There is therefore no randomized arm-to-arm estimate in the registry record.
Random allocation, when used, helps make groups comparable on average with respect to measured and unmeasured characteristics. That feature is not applicable to this trial's listed design. Without a comparator, changes or events observed during follow-up can reflect the natural course of illness, other care, measurement practices, or participant characteristics as well as any intervention effect. This is a general limitation of interpreting within-group outcomes, not a finding that any particular factor affected these participants.
What does open label mean for interpretation?
In general, an open-label study does not mask the intervention assignment from participants and study personnel. The registry lists masking as none. Lack of masking can matter when outcomes involve judgment, reporting, clinical decisions, or ascertainment that could be influenced by knowledge of treatment. RT-PCR is the stated method for the primary endpoint, but the record does not describe laboratory masking, specimen procedures, positivity criteria, or endpoint adjudication. The potential influence of open-label conduct on this endpoint therefore cannot be assessed from the registry entry.
How should a participant count be understood?
The primary endpoint is a count of participants with viral shedding as determined by RT-PCR. In general, a count is an event summary; its interpretation depends on a clearly specified event definition, observation period, and denominator. The record gives a timeframe of 14 to 28 days and describes a population of 28 patients with COVID-19 pneumonia, but it does not provide the observed event count or further operational details. No rate, proportion, or additional count should be inferred from the endpoint title alone.
For binary outcomes, uncertainty can be described with a confidence interval. In general, a confidence interval indicates the range of values compatible with the observed data under a specified statistical method and its assumptions. It does not eliminate bias from study design or incomplete outcome ascertainment. No confidence interval or primary endpoint estimate is reported in the registry record, so precision cannot be evaluated for this outcome.
Why does over-dispersion matter in some analyses?
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small if the model fails to account for that extra variability, leading to confidence intervals that are too narrow and tests that are too optimistic. Whether over-dispersion is relevant depends on the outcome and model. The registry record lists a participant-count endpoint and no analyses; it does not report a model or a dispersion estimate. There is no basis for claiming that over-dispersion was assessed or adjusted for in this trial.
What can a planning calculation tell readers?
In general, sample-size calculations are planning tools. They describe the number of participants an assumed design would require to detect an effect under specified assumptions; they do not show that an effect was observed or establish the precision of an actual trial result. The registry-related planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. It also distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. These are planning assumptions, not evidence that this single-group trial used a two-arm design. The record does not report the trial's own sample-size justification, so the planning description should not be treated as its protocol or design rationale.
Likewise, statistical power is a property of a design under assumptions, not a measure of whether a completed study found a real effect. In general, a retrospective power calculation based on an observed estimate does not replace reporting that estimate and its uncertainty. The registry record contains no primary analysis result to interpret, and no analysis count is reported. Thus, there is no posted basis for assessing a trial-specific power calculation or an inferential test of the primary outcome.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Hydroxychloroquine and Azithromycin | 28 | 6 | 21.4% | 8.3% to 41.0% | 10.2% to 39.5% | 10.3% to 39.7% |
R code and output
arm <- c("Hydroxychloroquine and Azithromycin")
n <- c(28)
events <- c(6)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Hydroxychloroquine and Azithromycin 28 6 21.4 8.3 41.0 10.2 39.5 10.3 39.711. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and no analyses. The named primary outcome concerns participants with viral shedding determined by RT-PCR, within a stated timeframe of 14 to 28 days. However, its result and any statistical analysis are not reported in the registry record. The record also does not report a statistical analysis plan, a hierarchy of outcomes, or a procedure for controlling multiplicity.
In general, multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. As the number of analyses increases, the chance of a nominally unusual result arising by chance can increase unless the analysis strategy accounts for it. The registry's listing of one outcome measure does not establish that only one analysis was conducted, especially because the registry reports no analyses. Whether multiple analyses were planned or performed is not reported in the registry record.
Missing outcome information is another distinct issue. The record gives a population description but does not state how many participants had an evaluable RT-PCR result, whether any measurements were missing, or how missing results were handled. It does not report the timing or completeness of sample collection. In general, missingness can affect both the estimated outcome and its uncertainty, particularly when missingness is related to health status or the outcome itself. The registry entry does not permit assessment of that possibility.
The analysis population is also not described beyond the outcome's population wording. The record does not state whether the primary analysis included all enrolled participants, only those with available measurements, or another defined group. These details are not reported in the registry record, so the analysis denominator and handling of incomplete follow-up cannot be reconstructed.
12. 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 |
|---|---|---|---|
| Hydroxychloroquine and Azithromycin | 9 | 28 | 32.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Hydroxychloroquine and Azithromycin | 28 of 28 |
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 |
|---|---|
| Hydroxychloroquine and Azithromycin | 0 of 28 |
Most frequent serious adverse event terms
| Event term | Organ system | Hydroxychloroquine and Azithromycin |
|---|---|---|
| Clotting to vital organs (lungs, heart, kidney and brain) | Respiratory, thoracic and mediastinal disorders | 9 of 28 |
Serious events with the highest arm-level rate: clotting to vital organs (lungs, heart, kidney and brain) (32.1%).
The safety entry lists 9 participants affected by serious adverse events among 28 at risk. It lists 0 participants affected by other adverse events among 28 at risk. These are counts reported for the single hydroxychloroquine and azithromycin group; there is no comparator group for a between-group safety contrast.
The listed top serious-event term is “Clotting to vital organs (lungs, heart, kidney and brain),” with 32.1%. The registry entry does not state the denominator or calculation details for that percentage in the information available, so it should not be converted into a count or assumed to describe a particular share of participants or events.
The record lists deaths as 28. It does not provide explanatory context for this entry alongside the other safety counts. For that reason, the value should be quoted as recorded but treated as requiring verification rather than reconciled by assumption. The record does not give details about timing, cause, or attribution. In general, adverse-event counts describe reported events in a study group; without a comparator and fuller event definitions, they do not by themselves establish whether an intervention caused an event.
13. What the Result Does, and Does Not, Mean
This trial record identifies a prospective, open-label, non-comparative study of hydroxychloroquine and azithromycin in hospitalized patients with moderate or severe COVID-19. It specifies viral shedding measured by RT-PCR as the primary outcome and gives a timeframe of 14 to 28 days. It also contains safety entries for serious events, other events, a serious-event term, and deaths. These details describe the registered study and the entries in its record.
The actual primary endpoint result is not reported in the registry record. Accordingly, the record does not show the number of participants with viral shedding, how long shedding continued, or how precise any estimate was. No effect estimate or statistical test for the primary outcome is reported. The information cannot establish a reduction or increase in viral shedding, nor can it support a claim that the combination did or did not produce a particular outcome.
Even if a within-group endpoint estimate were available, a single-group design would not show how outcomes compared with an alternative. The record contains no randomized control group, and its allocation is listed as not applicable. A difference from a hypothetical or historical outcome would require additional assumptions and information not reported in the registry record. Such a comparison should not be presented as if it were a randomized finding.
The serious adverse-event entries deserve similarly bounded interpretation. They report counts and a term percentage but do not provide the detail needed to understand event timing, causality, or the percentage denominator. The deaths entry is recorded as 28 and lacks contextual explanation in these data. It should be verified rather than reinterpreted. Overall, the registry record offers limited descriptive information, not a complete account of outcomes or a basis for medical advice.
14. Why This Trial Matters Statistically
Statistically, this trial illustrates the difference between a registered research question and a reported result. A clearly named endpoint and a stated measurement method do not provide the observed data needed to estimate an outcome. Here, the registry identifies RT-PCR viral shedding as the primary endpoint but does not report its result. Readers therefore need to distinguish the endpoint description from evidence about what participants experienced.
The design also makes the limits of non-comparative evidence visible. A single-group study can describe outcomes in the enrolled group, while a treatment comparison requires a suitable reference group and an analysis that supports that contrast. The absence of a comparator is not merely a missing table row: it changes which questions the design can answer. The registry does not support an estimate of a causal difference between treatments.
The safety entries show why denominator, event definition, and context matter. Counts at risk and affected are reported, but the serious-event term's percentage lacks an accompanying denominator in these data, and the deaths entry is not explained. Statistical summaries are only interpretable when readers can connect them to clear definitions and populations. Ambiguous entries should be identified as such rather than silently harmonized.
Finally, the record distinguishes a planning illustration from the trial's own design. Planning assumptions about equal allocation between two arms do not turn a listed single-group trial into a comparative study, and planning calculations do not constitute observed power. This is a useful reminder that design labels, outcome results, and planning exercises answer different questions. The absence of a reported analysis also means that inferential methods and their assumptions cannot be evaluated for the primary outcome.
15. 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 most important limitation for interpretation is that the primary outcome result is not reported in the registry record. The entry names a participant-count endpoint but gives no observed count, duration estimate, confidence interval, or test result. Consequently, the statistical magnitude and precision of the primary outcome cannot be assessed.
The study is identified as single group and non-comparative, with no randomized comparator. Any outcome description from the treated group alone would not establish how the same population would have fared under another intervention or no intervention. The record also states that the trial was open label and lists no masking.
Some study descriptions are not fully aligned: the trial title refers to ICU patients, while the official title and outcome wording refer to hospitalized patients with moderate or severe infection. The record does not explain that difference. It does not report detailed eligibility criteria, the endpoint's operational definition, specimen collection procedures, or rules for missing measurements. It also does not state the trial's sample-size justification or a statistical analysis plan.
The safety information is limited to listed counts, one serious-event term and percentage, and the deaths entry. Details needed to interpret timing, attribution, event recurrence, and the percentage denominator are not reported in the registry record. In particular, the record lists deaths as 28 but does not explain the entry in the information available. These limitations prevent a fuller safety interpretation and should not be filled in by assumption.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Non-comparative Trial of the Combination of HCQ and AZI in the Treatment of ICU Patients — NCT04458948.
- Registry record last updated 2023-09-13; status last verified 2023-08.
- Results first posted 2023-09-13.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry record describes a Phase 2, open-label, prospective, non-comparative, single-group trial sponsored by the University of New Mexico. All subjects received hydroxychloroquine and azithromycin. The stated population concerns hospitalized patients with moderate or severe COVID-19, and the primary-outcome description refers to 28 patients with COVID-19 pneumonia.
The primary endpoint is the number of participants with viral shedding determined by RT-PCR, with a timeframe of 14 to 28 days. Its result is not reported in the registry record. The record lists one outcome measure and no analyses, and the trial status is terminated.
Safety entries include 9 participants affected by serious adverse events among 28 at risk, 0 affected by other adverse events among 28 at risk, a serious-event term with 32.1%, and deaths listed as 28. The available record does not provide enough context to resolve the deaths entry or fully interpret the serious-event percentage.