Prazosin to Prevent COVID-19 (PREVENT-COVID Trial): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (NCT04365257), a randomized phase 2 study. The primary outcome is Death.

2. Clinical Question

The clinical question is therefore a comparison of participant counts for death between a prazosin arm and a standard-of-care arm. The record describes a randomized study, but it does not provide an estimable between-arm analysis for this binary endpoint. The posted counts are 0 deaths among 3 participants assigned to prazosin and 0 among 2 assigned to standard of care. These observations describe the enrolled participants; they do not establish that the arms have the same underlying risk.

The broader stated aim concerns prevention of cytokine storm syndrome and severe complications. However, the primary endpoint posted for this record is death, not a direct measure of cytokine storm syndrome. The registry record lists laboratory outcomes among its secondary outcomes, but does not post analyses for them. Details about how participants were selected, the clinical criteria used to assess cytokine storm syndrome, and the other severe complications targeted are not reported in the registry record.

3. Trial Design

This was a phase 2, randomized, open-label, parallel-group study comparing prazosin with standard of care in hospitalized patients with COVID-19. The record identifies Johns Hopkins University as the sponsor. Enrollment was 5 participants. The study started on 2020-05-13, had a primary completion date of 2022-03-31, and is listed as terminated.

Three participants were assigned to prazosin and 2 to standard of care. Because masking is listed as none, the study was open-label: treatment assignment was not masked according to the registry record. The record does not explain why the study was terminated, whether termination occurred before planned enrollment was complete, or whether the planned enrollment target changed. Those details are not reported in the registry record.

The prazosin arm description begins with 1mg to assess tolerance and symptoms of hypotension, with continued dosing described conditionally. The available description is incomplete, so the full regimen and any changes to it are not reported in the registry record. The standard-of-care arm is described as receiving standard of care, without a more detailed account of its components.

Randomization is intended to allocate participants among treatment groups by chance, reducing systematic differences in expectation. In a small study, however, randomization cannot ensure that groups have similar characteristics, and the record does not provide baseline characteristics with which to assess their balance. A parallel-group design assigns participants to an arm for comparison rather than describing a crossover. The registry record does not report the allocation sequence, concealment procedures, recruitment target, or detailed statistical plan. The very small enrollment means that the posted counts represent only a few participants and provide limited information for comparing outcomes.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Death, measured over up to day 60.

The primary endpoint is death, recorded as the number of participants in each arm who expired, with a timeframe of up to day 60. This is a binary outcome at the participant level: each participant either experienced the event during the stated timeframe or did not. The posted results report 0 deaths among 3 participants in the prazosin arm and 0 among 2 participants in the standard-of-care arm.

Death is a clinically consequential endpoint and can be counted without relying on a subjective symptom scale. It is also a relatively uncommon event in many study settings, so a small trial may observe few or no events. When no events are observed in either arm, the data cannot distinguish between genuinely similar underlying risks and different risks that the small study was unable to reveal. A zero count is an observation in the enrolled participants, not proof that the event cannot occur.

The registry record gives the endpoint timeframe but does not report additional details such as how deaths were ascertained, how participants lost to follow-up were handled, or whether the endpoint was assessed by a masked reviewer. Those details are not reported in the registry record. The primary endpoint is not itself a direct measurement of the study’s broader stated aim of preventing cytokine storm syndrome. The record lists laboratory outcomes as secondary outcomes, but analyses for those outcomes are not posted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being counted?

Death is a binary participant-level outcome. For each participant, the event status is either event or no event within the specified timeframe. The posted arm summaries give the number of participants with the event and the number enrolled in each arm. In this study, the recorded event counts are zero in both groups, with 3 participants in the prazosin arm and 2 in the standard-of-care arm.

General statistical explanation: binary outcomes are often compared using a difference in event proportions, a relative measure, or a model-based estimate. Each approach needs data and assumptions suited to the study. When both arms have zero observed events, common comparative estimates can become undefined or fail to convey useful information. The registry record explicitly states that the two-arm comparison is not estimable. No alternative method or adjusted estimate is reported.

What does not estimable mean?

In general, an estimate is not estimable when the available data and chosen calculation do not yield a usable numerical value for the target comparison. This is not the same as estimating no difference with high precision. In this record, the zero event counts provide no observed difference in counts, but they do not establish equal underlying event risks. The registry record does not report a confidence interval, p-value, or model-based comparison for the primary endpoint.

With very few participants and no observed events, uncertainty about the underlying event risk is substantial as a matter of general statistical reasoning. The data cannot show whether the underlying risks are close or meaningfully different. A method designed for sparse binary data might express uncertainty differently from a large-sample approximation, but the registry record does not report a method for estimating the primary comparison. It would be inappropriate to attribute an unreported method to the investigators.

How should the planning illustration be understood?

The registry’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. For time-to-event outcomes, the illustration is expressed as a total number of events; for other outcomes, it is expressed as participants per arm. Such a calculation is a planning illustration, not an observed result and not a measure of the probability that this trial detected an effect.

In general, a sample-size calculation depends on assumptions about the effect one wants to detect, the statistical method, and the desired operating characteristics. Its output indicates a planning requirement only under those assumptions. It cannot establish that a study was adequately powered after the fact, and it does not repair the uncertainty caused by sparse observed data. The trial’s own sample-size justification and design assumptions are not reported in the registry record. No specific planning estimate should be interpreted as the number actually enrolled or as evidence about the outcome.

Why can over-dispersion matter?

General explanation: over-dispersion means that observed variation is greater than a model expects. It matters in analyses of counts or rates because a model that assumes too little variation can make uncertainty appear smaller than it is. The primary outcome is a binary participant count, and the registry record does not report a model for it or evidence that over-dispersion was assessed. Therefore, over-dispersion should not be treated as a feature of the reported primary analysis. It is a general consideration when choosing models for count data, not a finding from this trial.

What is reported about analyses?

The registry record lists 10 outcome measures and 0 analyses. It identifies death as the primary outcome and lists four secondary outcomes concerning the number and duration of laboratory abnormalities in peripheral blood and plasma. The record does not post inferential analyses for those outcomes. The statistical analysis plan, handling of covariates, and any planned interim analyses are not reported in the registry record. No particular model, test, or adjustment strategy can therefore be attributed to the study.

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.

R code and output

arm    <- c("Prazosin", "Standard of Care")
n      <- c(3, 2)
events <- c(0, 0)
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  Prazosin  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Standard of Care  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures, including the primary outcome of death and four named secondary outcomes concerning laboratory abnormalities in peripheral blood and plasma. It reports 0 analyses. No results for the secondary outcomes are posted in the information described by the registry record. The record does not specify whether additional outcomes were planned, how outcome families were defined, or whether any adjustment for multiple comparisons was planned or used. A multiplicity strategy is therefore not reported in the registry record.

General statistical context: when researchers test multiple outcomes or make multiple comparisons, the chance of at least one apparently unusual result can increase if each test is interpreted separately. Methods for addressing multiplicity may control error rates or prioritize a small set of outcomes. Whether such an approach was appropriate cannot be determined from the posted information, and no specific adjustment should be assumed.

Information about missing data, withdrawals, loss to follow-up, and the handling of participants without complete outcome assessment is not reported in the registry record. The posted enrollment and outcome counts do not explain whether all participants completed follow-up through day 60. The analysis population is also not reported: the record does not state whether the intended analysis was based on randomized assignment, treatment received, or another defined group. These omissions limit assessment of how fully the posted counts represent all randomized participants and how the analysis was intended to preserve the randomized comparison.

The record’s count of 0 analyses does not establish what analyses may have been conducted outside the registry; it means no analyses are posted in the registry record. The registry record also does not report a statistical analysis plan that would clarify which outcomes and methods were specified before results were available.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted safety figures report 0 serious adverse events among 3 participants in the prazosin arm and 0 among 2 participants in the standard-of-care arm. The record also reports 1 other adverse event among 3 participants assigned to prazosin and 1 among 2 assigned to standard of care. No deaths are listed in either group. The record does not identify the terms for serious adverse events among its top serious terms.

These are participant counts, not comparisons adjusted for exposure time or participant characteristics. With so few participants, the counts cannot provide a precise estimate of the frequency of adverse events in a broader population. A count of zero in the enrolled group does not establish that the risk is absent. Likewise, the presence of an adverse event in a group does not, by itself, establish that the assigned treatment caused it.

The registry record does not provide event descriptions for the other adverse events, their severity, timing, relationship to treatment, or the criteria used to classify seriousness. It also does not report exposure duration in a way that permits a safety-rate comparison. The figures should therefore be read as the reported counts in each arm, not as proof of safety or harm.

13. What the Result Does, and Does Not, Mean

The result means that no deaths were recorded among the 3 participants assigned to prazosin or the 2 assigned to standard of care through day 60. It also means that the registry record does not provide an estimable statistical comparison for this binary endpoint. The posted counts describe what happened in this small enrolled group; they do not establish the relative effect of the two treatment strategies.

The result does not show that the underlying risks are identical. It does not rule out a difference in either direction, because a small number of participants and no observed events provide little information about the range of plausible underlying risks. There is no reported confidence interval or p-value for the primary comparison with which to quantify statistical uncertainty.

The trial’s stated purpose was to assess prazosin for prevention of cytokine storm syndrome and severe complications in hospitalized patients with COVID-19. The posted primary endpoint is death, and the registry record does not post analyses of the listed laboratory outcomes. Consequently, the available counts do not establish whether prazosin affected cytokine storm syndrome, laboratory abnormalities, or other severe complications.

The record identifies the study as phase 2 and terminated, but does not report the reason for termination or the trial’s planned enrollment target. Those details cannot be used to infer why only 5 participants were enrolled. The most defensible reading is descriptive: the posted record documents zero deaths in both arms, other adverse events in each arm, and no estimable primary comparison. It does not settle the clinical question posed by the study.

14. Why This Trial Matters Statistically

This trial illustrates a central issue in clinical research: a randomized design does not automatically produce a precise answer when enrollment is very small and the outcome is not observed. Randomization is a valuable design principle, but the amount of information available for estimating treatment differences still depends on the observed data. Here, the registry record reports 5 participants in total and no deaths in either arm, leaving the primary comparison not estimable.

The record also shows why outcome choice and outcome availability matter. The stated research aim concerns prevention of cytokine storm syndrome and severe complications, while the primary outcome is death up to day 60. The registry record lists laboratory measures as secondary outcomes, but posts no analyses. Without those results, the broader biological and clinical questions cannot be evaluated from the registry record.

Finally, the record highlights the importance of transparent reporting. Information about the reason for termination, the planned enrollment, missing-data handling, analysis populations, multiplicity, and the statistical plan is not reported in the registry record. These details would help readers distinguish a completed but small study from a study that stopped early for a particular reason, and would clarify how planned analyses relate to posted results. Their absence is a limitation on interpretation, not evidence about what happened outside the record.

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 main limitation is the very small enrollment: 5 participants, with 3 assigned to prazosin and 2 to standard of care. With no deaths observed, the primary binary comparison is not estimable according to the registry record. No comparative effect estimate, confidence interval, or p-value is posted. The counts therefore offer little precision about death risk beyond describing these enrolled participants through day 60.

The study is listed as terminated, but the reason for termination and its relationship to the planned enrollment are not reported in the registry record. It is not possible to determine from the posted information whether enrollment stopped early, whether the target changed, or why the listed enrollment was 5. Baseline characteristics are not reported in the registry record for this record, so the balance of prognostic factors between randomized arms cannot be assessed.

The study was open-label, with no masking listed. The registry record does not report whether outcome assessment was independently masked or how deaths and adverse events were ascertained. Full details of the prazosin regimen are not reported in the registry record, and the standard-of-care arm is not described beyond its name. The record also does not report missing-data handling, analysis populations, a statistical analysis plan, or a multiplicity approach.

Although laboratory outcomes are listed among the secondary outcomes, the registry record reports 0 analyses. Thus, those outcomes cannot provide additional evidence about the study’s broader aim. The safety counts are also based on the same small groups and lack event descriptions and exposure-adjusted rates. These limitations restrict both efficacy and safety interpretation; they do not imply a particular direction of treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) — NCT04365257.
• Registry record last updated 2023-04-10; status last verified 2023-03.
• Results first posted 2023-01-31.
• 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.

19. Record Summary

NCT04365257 is the PREVENT-COVID Trial, a phase 2 randomized, open-label, parallel-group study sponsored by Johns Hopkins University. It compared prazosin with standard of care in hospitalized patients with COVID-19. Enrollment was 5, with 3 participants in the prazosin arm and 2 in the standard-of-care arm. The study started on 2020-05-13, had a primary completion date of 2022-03-31, and is listed as terminated.

The primary outcome was the number of participants who died up to day 60. The posted count was 0 in each arm. The registry record states that a two-arm comparison for this binary endpoint was not estimable. It lists 10 outcome measures and 0 analyses, including no posted analyses of the four listed secondary laboratory outcomes. The record does not report the reason for termination, a detailed statistical plan, or the intended analysis population.