Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post-Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses in Elderly Residents of Long-Term Care Facilities (LTCF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post-Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses in Elderly Residents of Long-Term Care Facilities (LTCF) (NCT04343248), a randomized phase 3 study. The primary outcome is Symptomatic Laboratory-confirmed COVID-19.

2. Clinical Question

The trial asked whether nitazoxanide, given after exposure, was associated with a different proportion of elderly long-term care facility residents developing symptomatic, laboratory-confirmed COVID-19 during treatment than placebo. The primary outcome was assessed through the end of the six-week treatment period. The record also lists hospitalization and mortality due to COVID-19 or complications, and the presence of anti-SARS-CoV-2 at weeks 6 or 8, as secondary outcomes.

The comparison is specifically about the recorded primary outcome over the stated follow-up window. It does not, by itself, address every respiratory illness or every possible benefit or harm. Although the trial title and summary refer to COVID-19 and other viral respiratory illnesses, the primary endpoint is symptomatic, laboratory-confirmed COVID-19. The registry record does not report statistical analyses for that endpoint, so the posted outcome figures do not establish a statistically supported difference between the assigned groups.

3. Trial Design

This was a phase 3, randomized, triple-masked, parallel-group trial sponsored by Romark Laboratories L.C. Its stated purpose was to evaluate the efficacy and safety of nitazoxanide for post-exposure prophylaxis of COVID-19 and other viral respiratory illnesses in elderly residents of long-term care facilities. The registry lists an enrollment of 190 and records the trial status as terminated.

The nitazoxanide arm is described as receiving two 300 mg tablets orally twice daily for six weeks. The placebo arm is described as receiving two placebo tablets on the same schedule and for the same duration. Vitamin Super B-Complex is also listed among the interventions, but an arm description or role for it is not reported in the registry record. The record identifies the design as randomized and triple-masked; it does not report further details about who was masked or how masking was maintained.

The recorded start date is 2020-05-12, and the primary completion date is 2021-02-01. The trial was terminated early, and the primary-outcome description states that no statistical analyses were performed because enrollment was terminated early. The registry record does not report why the trial was terminated or give further details about the circumstances of termination.

The primary efficacy population is defined as participants who received at least one dose of study medication and were negative for all respiratory viruses at baseline. The primary endpoint concerns events identified after treatment started and before the end of the six-week treatment period. The registry also lists three secondary outcomes: hospitalization due to COVID-19 or complications, mortality due to COVID-19 or complications, and anti-SARS-CoV-2 presence at weeks 6 or 8. Results for those outcomes are not reported in the registry record.

Randomization and masking are features of the planned design, but their presence does not substitute for reported outcome analyses. The registry record does not report the method of random sequence generation, allocation concealment, detailed masking procedures, or a statistical analysis plan. Those details should not be inferred from the design labels alone.

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:

Analysis population for the primary outcome, as defined in the registry: The primary efficacy population consists of all subjects who received at least one dose of study medication and were negative for all respiratory viruses at Baseline. Proportions rounded to the nearest hundredth.

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 safety population includes all subjects who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Symptomatic Laboratory-confirmed COVID-19, measured over up to 6 weeks.

The primary endpoint is the proportion of participants with symptomatic, laboratory-confirmed COVID-19 identified after the start of treatment and before the end of the six-week treatment period. It combines symptoms with laboratory confirmation, so it is narrower than an endpoint counting all infections, all respiratory illness, or laboratory positivity without symptoms. The defined efficacy population includes participants who received at least one dose of study medication and were negative for all respiratory viruses at baseline.

A proportion is a binary-outcome summary: each participant either meets the endpoint definition during the specified window or does not. It provides an interpretable description of how often the outcome occurred in a group, while a comparison between groups is needed to describe a treatment contrast. The registry says that the proportions are rounded to the nearest hundredth.

This endpoint is used to focus the primary question on symptomatic COVID-19 arising during the treatment period. Its interpretation depends on the endpoint definition, baseline eligibility, follow-up window, and completeness of outcome ascertainment. The record does not report additional details about laboratory testing procedures, symptom criteria, or how missing outcome information was handled. It also states that no statistical analyses were performed after early termination. Therefore, the posted proportions are descriptive registry results rather than a reported inferential analysis of the primary question.

7. Results Posted in the Registry

• Nitazoxanide: 0.0% (0/85) versus 0.0% (0/81) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because it classifies participants according to whether they met the definition of symptomatic, laboratory-confirmed COVID-19 within the specified treatment window. For a binary endpoint, a group proportion describes the frequency of participants meeting the definition in that group. The registry reports proportions rounded to the nearest hundredth. A rounded proportion can conceal some detail, so it should not be treated as a full account of the underlying event data.

What does a risk difference describe?

In general, a risk difference is the proportion with an outcome in one group minus the proportion with the outcome in the comparison group. It expresses the absolute contrast on the proportion scale. The posted comparison records a risk difference of 0.0 and records zero events in each group. That is the comparison output in the registry; it is not a new calculation from the rounded arm summaries. Because the primary outcome description states that no statistical analyses were performed, the comparison output should be read cautiously and not as a completed inferential analysis.

What do confidence intervals and p-values add?

In general, a confidence interval describes the uncertainty around an estimate under a specified statistical method and assumptions. A p-value summarizes how compatible data are with a specified null hypothesis under a statistical model; it is not the probability that the null hypothesis is true. Neither measure replaces the effect estimate or addresses all design and data-quality concerns. No primary-outcome confidence interval or p-value is reported in the registry record. The record also does not report a statistical analysis plan that would establish which inferential methods were intended.

Why does early termination matter?

The primary-outcome description says the trial stopped enrollment early and that no statistical analyses were performed. When fewer outcome observations are available than intended, estimates may be less precise, and the information available may be insufficient for a planned comparison. The registry record does not report the planned enrollment target, the reason for termination, any interim analyses, or whether any formal stopping rule was used. It would be inappropriate to infer any of these details. The recorded enrollment is not a substitute for a documented design target or a completed analysis.

How should the posted summaries be distinguished?

The arm summaries report proportions of 0.01 and 0.0. The comparison output separately reports zero events in both groups and a risk difference of 0.0. The registry does not explain why these entries differ in their apparent event information. Rounding can affect descriptive proportions, but the record does not identify rounding as the explanation for this particular difference. The safest interpretation is to report both entries as recorded and avoid using either to reconstruct unreported event counts or an alternative estimate.

What do the planning illustrations mean?

In general, sample-size calculations ask how many participants would be needed under specified assumptions to detect a chosen effect with a chosen statistical operating characteristic. The planning illustrations associated with the posted results are described as based on the observed effect, rather than the trial's own design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. These are planning illustrations, not evidence that the trial was designed around those assumptions or that it achieved a particular power.

When an observed effect is used to construct a planning illustration, the result is conditional on that observed estimate and the calculation assumptions. Such a calculation does not show the probability that the completed trial detected an effect, and it is not observed power. The record does not report the trial's original sample-size justification or design assumptions. No numeric planning estimates are stated in the registry information, so no participant requirements can be inferred from the assumptions alone.

In general, the choice of analysis population matters because excluding participants or restricting eligibility can change the group being described and the interpretation of the estimate. The registry defines a primary efficacy population based on receiving at least one dose and being negative for all respiratory viruses at baseline. It does not report a detailed account of how many participants met each condition, how missing observations were handled, or whether other analysis populations were used. The posted summaries should therefore not be assumed to represent an intention-to-treat analysis or any other population beyond the descriptions attached to them.

These methodological distinctions are especially important when the record contains descriptive proportions but no reported inferential analysis. The proportion describes an outcome frequency as recorded; a contrast describes a difference between groups; and uncertainty measures describe the precision of that contrast under stated assumptions. They answer related but different questions. The registry record supplies descriptive entries and a separate comparison output, but does not document a complete statistical analysis of the primary endpoint.

10. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated outcome or group contrast. In general, a confidence interval gives a range of values compatible with the data and a specified method, subject to the method's assumptions. A narrow interval indicates greater statistical precision than a wide interval, but an interval does not resolve possible biases, endpoint misclassification, or limitations in the design.

No confidence interval for the primary outcome or its treatment contrast is reported in the registry record. The comparison output lists lower and upper bounds of 0.0, but the primary-outcome description says that no statistical analyses were performed. Those recorded bounds should not be interpreted as a meaningful uncertainty interval demonstrating perfect precision. The registry does not report the method or inferential interpretation for those bounds.

The arm proportions are rounded to the nearest hundredth, which limits the detail available in those descriptive summaries. The registry also presents a separate comparison entry recording zero events in both groups, without explaining its relationship to the arm proportions. This difference in presentation makes it particularly important not to infer an unreported confidence interval or reconstruct a more precise estimate from the rounded values.

The registry's planning illustrations are not a substitute for uncertainty intervals around the trial results. They are described as calculations based on the observed effect, using specified assumptions, and are intended as planning illustrations rather than observed power. The original design calculation and the trial's statistical plan are not reported in the registry record. Accordingly, the primary result should be described as lacking a reported precision estimate, rather than as precisely null or precise evidence of a difference.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: hospitalization due to COVID-19 or complications, mortality due to COVID-19 or complications, and the presence of anti-SARS-CoV-2 at weeks 6 or 8. Their listing identifies additional questions the trial was set to assess, but results for these outcomes are not reported in the registry record. The record lists five outcome measures overall, but does not provide a statistical analysis plan explaining how primary and secondary outcomes were to be analyzed.

In general, testing multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance if each is tested separately. A prespecified multiplicity strategy can address that issue, but the record does not report whether any such strategy was planned. There are no reported secondary-outcome analyses from which to assess multiplicity in practice. No adjustment method, hierarchy of testing, or distinction between confirmatory and exploratory analyses is reported in the registry record.

The registry defines the primary efficacy population as participants who received at least one dose and were negative for all respiratory viruses at baseline. It does not report participant-level missingness, reasons for missing outcome data, imputation methods, or sensitivity analyses. It also does not report whether all randomized participants were included in the posted primary summaries. The different denominators appearing in the efficacy and adverse-event summaries should not be assumed to describe identical analysis populations.

These omissions limit what can be concluded about the completeness and robustness of the reported results. The registry record states that no statistical analyses were performed for the primary endpoint because enrollment was terminated early. The record does not report interim analyses or additional missing-data procedures. In general, missingness can affect both the amount of information available and the interpretation of group comparisons; without details, its impact cannot be assessed for this trial.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest (1.1%), cardiovascular disorder (1.1%), diarrhoea (1.1%), urinary tract infection (1.1%), musculoskeletal chest pain (1.1%).

The safety summaries use denominators of 97 for nitazoxanide and 93 for placebo. The registry records serious adverse events affecting 10 participants in the nitazoxanide group and 8 in the placebo group. It records other adverse events affecting 8 and 9 participants, respectively. The death counts are 1 for nitazoxanide and 2 for placebo. These are the posted group summaries; they should not be interpreted as a causal comparison or as proof that an event was caused by study medication.

The registry lists six serious adverse-event terms at 1.1% each: cardiac arrest, cardiovascular disorder, diarrhoea, urinary tract infection, musculoskeletal chest pain, and cerebrovascular accident. These entries identify reported event terms; the record does not provide further context about timing, severity details, relatedness assessments, or whether any participant had more than one event. The terms and group-level counts do not establish how events were distributed across individuals.

In general, adverse-event summaries depend on the population monitored, the event definitions, and the way events are counted. The safety denominators differ from those in the primary efficacy summaries, and the registry record does not explain the relationship between those populations. The figures describe what was recorded, not a complete assessment of comparative safety or causation.

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

The posted results describe a randomized comparison of nitazoxanide and placebo in elderly long-term care facility residents, with a primary endpoint of symptomatic, laboratory-confirmed COVID-19 during a six-week treatment period. The registry reports arm proportions of 0.01 for nitazoxanide and 0.0 for placebo. A separate comparison output records zero events in both groups and a risk difference of 0.0. The record does not explain the relationship between these entries, and it explicitly states that no statistical analyses were performed after early termination.

These registry entries support a descriptive account of what the registry records, but they do not establish whether the groups differed statistically or whether any difference is compatible with chance. No primary-outcome confidence interval or p-value is reported. The absence of an inferential analysis is not evidence that the treatments are equivalent, and the recorded risk difference of 0.0 should not be treated as proof that the underlying effect is exactly zero.

The record also does not provide results for the listed secondary outcomes of hospitalization, mortality, and anti-SARS-CoV-2 presence. Their inclusion in the registry does not show that a benefit or harm occurred. Likewise, the adverse-event summaries describe recorded counts and terms but do not establish that treatment caused an event or support a complete comparative safety conclusion.

Trial termination, lack of a reported analysis plan, and the unexplained difference between the primary arm summaries and the comparison output all constrain interpretation. The record does not state why enrollment was terminated, how missing outcome data were handled, or whether any interim analyses took place. Those details cannot be inferred from the posted outcome entries.

The appropriate conclusion is limited: the registry presents descriptive primary and safety results, while noting that no statistical analyses were performed for the primary outcome. The results do not provide a reliable inferential estimate of treatment effect, and they cannot by themselves resolve whether nitazoxanide differs from placebo for this endpoint.

14. Why This Trial Matters Statistically

This trial is statistically important as an example of the difference between having outcome numbers and having an interpretable treatment-effect analysis. The record includes rounded primary proportions and a separate risk-difference output, but explicitly says that no statistical analyses were performed because enrollment was terminated early. A numerical result without an accompanying, documented analysis cannot answer all the questions readers may expect about uncertainty or group differences.

The record also illustrates why outcome definitions and analysis populations matter. The primary endpoint is symptomatic, laboratory-confirmed COVID-19 within a defined treatment window, and the efficacy population is restricted by treatment receipt and baseline respiratory-virus status. Those choices specify what the endpoint summaries describe. They do not automatically make the results generalizable to other populations, outcomes, or follow-up periods.

Early termination can leave a study with less information than intended, but the registry does not report the reason for termination or the original design assumptions. Those missing details limit assessment of whether the planned question could be answered. It would be inappropriate to infer a sample-size target, a stopping rule, or the study's intended statistical power from the posted enrollment alone.

The safety results offer another statistical lesson: group counts are tied to their own denominators and event definitions. The adverse-event denominators differ from the primary-outcome summaries, and the record does not explain the population relationship. Keeping those summaries separate avoids implying a common analysis population or a causal interpretation that the registry does not report.

Finally, the record shows the value of distinguishing a lack of statistical evidence from evidence of no effect. With no reported primary-outcome inference and no confidence interval, the precision and compatibility of possible treatment effects cannot be judged from the registry record. That distinction is essential when communicating incomplete trial results.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The main limitation is explicit in the registry: enrollment was terminated early, and no statistical analyses were performed for the primary outcome. The record does not report the reason for termination, the original planned enrollment, any interim analyses, or the trial's statistical analysis plan. Without those details, the context for the termination and the intended analysis cannot be assessed.

The primary outcome is reported as rounded arm proportions, while the separate comparison output records zero events in each group and a risk difference of 0.0. The registry does not explain the relationship between these entries. No confidence interval or p-value for the primary endpoint is reported. This limits both the interpretation of the apparent group summaries and any assessment of precision.

The record defines a primary efficacy population but does not report a participant-flow account, missing-data handling, or whether the posted outcome population aligns with all randomized participants. Efficacy and adverse-event summaries use different denominators; their relationship is not reported. The record also does not report the laboratory testing procedures, symptom criteria, or detailed ascertainment methods for the primary endpoint.

Although secondary outcomes are listed, their results are not reported in the registry record. No multiplicity strategy is reported. The record does not explain the role of Vitamin Super B-Complex, which is listed as an intervention without a corresponding arm description. Masking is recorded as triple, but further details about who was masked and how are not reported.

These limitations restrict interpretation to the registry's descriptive entries. They do not establish that the endpoint was measured incorrectly or that the treatment had a particular effect; rather, they identify information that is not reported and analyses that were not performed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post-Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses in Elderly Residents of Long-Term Care Facilities (LTCF) — NCT04343248.
• Registry record last updated 2024-07-08; status last verified 2024-07.
• Results first posted 2024-07-08.
• 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

This phase 3, randomized, triple-masked, parallel-group trial evaluated nitazoxanide versus placebo for post-exposure prophylaxis of COVID-19 and other viral respiratory illnesses in elderly long-term care facility residents. The recorded enrollment is 190, and the registry status is terminated. The primary endpoint was symptomatic, laboratory-confirmed COVID-19 identified after treatment began and before the end of the six-week treatment period.

The registry reports primary arm proportions of 0.01 for nitazoxanide and 0.0 for placebo. Its separate comparison output records zero events in both groups and a risk difference of 0.0. The primary-outcome description states that no statistical analyses were performed because enrollment was terminated early. No primary confidence interval or p-value is reported. Results for the listed secondary outcomes are not reported in the registry record. The posted figures therefore permit only a limited descriptive interpretation, not a firm inferential conclusion about the treatment comparison.