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 Hydroxychloroquine as Post-Exposure Prophylaxis Against COVID-19 Infection (NCT04372017), a randomized phase 3 study. The primary outcome is Cohort A: Percentage of COVID-19 Exposed Healthcare Workers Treated With Hydroxychloroquine With a Positive COVID-19 Test..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04372017 |
| Phase | Phase 3 |
| Condition | COVID-19, SARS-CoV 2 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanford Health |
| Results posted | Yes |
2. Clinical Question
Population
The study planned to examine two cohorts: healthcare workers exposed to a known case of COVID-19, and high-risk participants. The primary outcome description concerns exposed healthcare workers. The eligibility criteria and definitions of exposure and high risk are not reported in the registry record. The record states that no subject data were analyzed and that the study was closed early.
Intervention
Hydroxychloroquine was the intervention being evaluated for post-exposure prophylaxis. The registry lists Vitamin D as an intervention as well, but its role in the study is not reported in the registry record. Dose, schedule, duration, and timing relative to exposure are also not reported in the registry record.
Comparator
The official title describes a placebo comparison. The arm descriptions identify hydroxychloroquine and placebo groups in both cohorts, but do not give further treatment details. The registry record does not report whether allocation was balanced in the enrolled participants or which cohort included the recorded enrollment.
Primary question
The primary outcome asks what percentage of exposed healthcare workers treated with hydroxychloroquine had a positive COVID-19 test. Its description frames the question as whether post-exposure prophylaxis can prevent COVID-19 in healthcare workers exposed to a known case. No outcome data or treatment comparison is reported, so the record cannot answer that question.
3. Trial Design
The registry describes a phase 3, randomized, double-blind, placebo-controlled study with a parallel design. Its official title identifies hydroxychloroquine versus placebo, and the brief summary describes two distinct cohorts. Cohort A comprised healthcare workers; Cohort B comprised high-risk participants. Each cohort has a hydroxychloroquine arm and a placebo arm in the registry listing. Detailed arm descriptions are blank, so treatment schedules and other arm-specific procedures are not reported in the registry record.
The sponsor was Sanford Health. The listed study start date is 2020-05-14, and the primary completion date is 2021-06-04. The status is terminated, and enrollment is recorded as 1. The primary outcome description says that no subject data was analyzed and that the study was closed early. The registry record does not explain why it was terminated or give further detail about the enrollment.
Randomization and double masking are design features intended to support a fair comparison and reduce the influence of expectations on treatment and outcome assessment. Those features describe the planned design; they do not establish that a treatment comparison was completed. With no subject data analyzed, the record does not report group-specific outcome results, an estimated treatment effect, or an uncertainty measure. The Vitamin D intervention is listed, but its connection to the study arms or objectives 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 | Cohort A: Healthcare Worker (Hydroxychloroquine) | Cohort A: Healthcare Worker (Placebo) | Cohort B: High-Risk Participant (Hydroxychloroqine) | Cohort B: High-Risk Participant (Placebo) |
|---|---|---|---|---|
| STARTED | 1 | 0 | 0 | 0 |
| COMPLETED | 1 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: No subject data was analyzed. Study was closed early.
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: No subjects or data analyzed. Study was closed to enrollment before analysis.
| Characteristic | Unit | Cohort A: Healthcare Worker (Hydroxychloroquine) | Cohort A: Healthcare Worker (Placebo) | Cohort B: High-Risk Participant (Hydroxychloroqine) | Cohort B: High-Risk Participant (Placebo) | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 1 | 0 | 0 | 0 | 1 | |
| Age, Categorical: <=18 years | Participants | 0 | — | — | — | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | — | — | — | 1 |
| Age, Categorical: >=65 years | Participants | 0 | — | — | — | 0 |
| Sex: Female, Male: Female | Participants | 0 | — | — | — | 0 |
| Sex: Female, Male: Male | Participants | 1 | — | — | — | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | — | — | — | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 | — | — | — | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | — | — | — | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | — | — | — | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | — | — | — | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | — | — | — | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | — | — | — | 0 |
| Race (NIH/OMB): White | Participants | 0 | — | — | — | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | — | — | — | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | — | — | — | 1 |
| Region of Enrollment: United States | participants | 1 | — | — | — | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Cohort A: Percentage of COVID-19 Exposed Healthcare Workers Treated With Hydroxychloroquine With a Positive COVID-19 Test., measured over At enrollment completion outcome 1 will be analyzed..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled as the percentage of COVID-19-exposed healthcare workers treated with hydroxychloroquine who had a positive COVID-19 test. Its description asks whether post-exposure prophylaxis with hydroxychloroquine can prevent COVID-19 among healthcare workers exposed to a known case. A positive test is therefore the recorded outcome of interest in this population, rather than a general measure of symptoms or illness severity.
In general, a percentage outcome can communicate how often an event occurred among the participants evaluated. To interpret it, readers need the number with a positive test and the total number assessed, along with a clearly defined assessment period and testing procedure. Those details and any observed percentage are not reported in the registry record. The timeframe says, “At enrollment completion outcome 1 will be analyzed.” It does not define when testing occurred relative to exposure or specify a testing protocol.
The registry lists two outcome measures, but the primary outcome is the only one described in the record details. No subject data was analyzed, so there is no observed endpoint result to compare between hydroxychloroquine and placebo. The outcome is relevant to the prevention question, but the stated objective and endpoint alone do not establish whether the intervention changed the chance of a positive test.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record does not report an efficacy result. It records enrollment of 1, but explicitly states that no subject data was analyzed and that the study was closed early. There is consequently no reported positive-test count, percentage, comparison between arms, or treatment-effect estimate for the primary outcome. A treatment effect cannot be judged from the trial results because the record contains no analyzed outcome data.
The randomized, double-blind, placebo-controlled design describes how the study was intended to compare treatment groups. Randomization can help balance measured and unmeasured participant characteristics on average, while masking can reduce the influence of treatment knowledge on care and outcome assessment. These are general design principles; they do not create evidence when the outcome comparison was not analyzed. The registry record also does not identify which cohort included the recorded enrollment or whether that person received either study treatment.
There is no reported confidence interval or p-value for the primary outcome. In general, a confidence interval describes the range of effect values compatible with the data and analysis under the method’s assumptions. A p-value, when reported, describes how unusual data at least as extreme as those observed would be under a specified null model. Neither statistic can be interpreted without an analyzed comparison, and neither is reported in the registry record. The record also does not report an adjusted or unadjusted estimate.
The adverse-event entries are separate from an efficacy analysis. They list small counts in the healthcare-worker hydroxychloroquine group and zeros in the other groups, but do not supply a treatment comparison or detailed event descriptions. Those entries cannot fill the gap in the primary outcome data. In particular, they do not show whether hydroxychloroquine prevented infection or establish a comparative safety profile.
The record’s enrollment and early closure limit what can be learned from the planned clinical question. No explanation for termination, analysis plan, or reason for the absence of subject-level outcome analysis is reported in the registry record. The appropriate reading is therefore descriptive: the record documents a planned trial and some adverse-event counts, but no analyzed efficacy result. It neither demonstrates benefit nor demonstrates lack of benefit.
9. Statistical Methods Explained
What randomization contributes
In general, randomization assigns participants to study groups by chance rather than by clinical judgment or participant choice. This can reduce systematic differences between groups and supports an interpretable comparison of outcomes. It does not guarantee that groups will be similar in a small enrollment, and it does not remove the need to report how many participants were assigned, treated, and analyzed in each group. The registry record identifies the design as randomized, but group-specific enrollment and analysis counts are not reported in the registry record.
Why masking matters
The record describes double masking and a placebo comparator. In general, masking can limit the effects of expectations on participant reports, clinician decisions, and outcome assessment. A placebo can help distinguish the effect of an intervention from changes that might occur in a comparison group. The registry record does not describe who was masked, how masking was maintained, or whether it was assessed. These missing details do not change the recorded design label, but they limit assessment of how the design was implemented.
How a percentage outcome is interpreted
The primary outcome concerns the percentage of exposed healthcare workers treated with hydroxychloroquine who had a positive COVID-19 test. In general, a percentage is a numerator—the number meeting the outcome—relative to a denominator—the number assessed in the relevant group. Interpretation depends on a consistent outcome definition, a specified period of observation, and complete enough testing and follow-up. A between-group analysis would also need results for the placebo group. The record does not report these counts, the testing definition, or a group comparison, and it states that no subject data was analyzed.
What uncertainty measures would add
In general, an effect estimate describes the observed contrast between groups, while a confidence interval communicates statistical uncertainty around that estimate. A narrower interval indicates greater precision under the analysis assumptions; a wider interval indicates less precision. A p-value is not a measure of the size or clinical importance of an effect. No effect estimate, confidence interval, or p-value for the primary outcome is reported in the registry record. Accordingly, there is no statistical precision to interpret for the efficacy question.
Why analysis choices matter
Clinical-trial analyses may use different populations, such as participants assigned to groups or participants who completed specified procedures. In general, these choices can affect the estimand and the conclusions, particularly when treatment discontinuation or missing outcomes occur. The registry record does not report an analysis population, a statistical analysis plan, or a method for handling missing data. Since the record states that no subject data was analyzed, it also gives no basis for assessing adherence to a planned analysis.
The record lists two outcome measures, but does not give details of the other outcome in the information. In general, when a study evaluates multiple outcomes or comparisons, the analysis plan should clarify which outcomes are primary and how inferential results will be interpreted. No multiplicity strategy or hierarchy beyond the named primary outcome is reported in the registry record. It is not possible to determine whether adjustments were planned or needed in an analysis that was not performed.
What the planning assumptions do and do not mean
In general, sample-size planning estimates the number of participants needed to detect a specified effect under chosen assumptions. Such an estimate is a planning illustration, not an observed result and not “observed power.” Here, the stated planning assumptions refer to a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of an observed effect. However, no observed primary-outcome effect is reported because no subject data was analyzed. The registry record does not report the trial’s own sample-size justification, and these assumptions should not be mistaken for evidence that the planned comparison was conducted.
Some event-based methods, in general, plan around the number of events rather than the number of participants. For time-to-event outcomes, event totals can be central because the information available for estimating a treatment contrast depends on events observed. The primary endpoint is a positive-test percentage, not a stated time-to-event outcome. No event-time analysis or time-to-event results are reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and identifies one primary outcome concerning positive COVID-19 tests among exposed healthcare workers treated with hydroxychloroquine. Details of the other outcome are not reported in the registry record. It does not describe a hierarchy among outcomes, a multiplicity adjustment, or how multiple comparisons were to be interpreted. Without an analysis, it is not possible to assess the implications of testing more than one outcome or comparison.
The record states that no subject data was analyzed. It does not report the number of participants assigned to each arm, the number assessed for the primary outcome, or the number with missing test results. Thus, the extent and pattern of missing outcome data cannot be evaluated. No imputation method, censoring rule, or other missing-data approach is reported in the registry record.
Analysis populations are also not specified. The record does not say whether an intention-to-treat, per-protocol, safety, or other population was planned or used. These terms refer generally to different rules for including participants in analyses; they can answer different questions and may produce different estimates. Since the record reports no subject-data analysis, none of these populations can be identified as the basis for an efficacy result.
It is not reported in the registry record whether interim analyses were planned or conducted. Nor does the record explain early closure. The status is terminated, but that status alone does not identify the reason or establish that any interim statistical decision was made. These omissions mean that multiplicity, missingness, and analysis-population choices cannot be reconstructed from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Cohort A: Healthcare Worker (Hydroxychloroquine) | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort A: Healthcare Worker (Hydroxychloroquine) | 0 of 1 |
| Cohort A: Healthcare Worker (Placebo) | 0 of 0 |
| Cohort B: High-Risk Participant (Hydroxychloroqine) | 0 of 0 |
| Cohort B: High-Risk Participant (Placebo) | 0 of 0 |
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 |
|---|---|
| Cohort A: Healthcare Worker (Hydroxychloroquine) | 1 of 1 |
| Cohort A: Healthcare Worker (Placebo) | 0 of 0 |
| Cohort B: High-Risk Participant (Hydroxychloroqine) | 0 of 0 |
| Cohort B: High-Risk Participant (Placebo) | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort A: Healthcare Worker (Hydroxychloroquine) | Cohort A: Healthcare Worker (Placebo) | Cohort B: High-Risk Participant (Hydroxychloroqine) | Cohort B: High-Risk Participant (Placebo) |
|---|---|---|---|---|---|
| diarrhea | Gastrointestinal disorders | 1 of 1 | 0 of 0 | 0 of 0 | 0 of 0 |
| Stomach pain | Gastrointestinal disorders | 1 of 1 | 0 of 0 | 0 of 0 | 0 of 0 |
| infections and infestations - Other, specify | Infections and infestations | 1 of 1 | 0 of 0 | 0 of 0 | 0 of 0 |
The registry’s adverse-event entries report counts by arm. In Cohort A, the hydroxychloroquine group lists 1 at risk and 0 affected for serious adverse events; it lists 1 at risk and 1 affected for other adverse events. The Cohort A placebo group and both Cohort B groups list 0 at risk and 0 affected in these categories. Deaths are listed as 0 in every group, and no top serious-event terms are listed.
These counts are descriptive entries, not comparative rates or evidence of causation. The record does not provide detailed event descriptions, timing, severity criteria, or an assessment of whether an event was related to treatment. It also does not explain the meaning of the at-risk counts or how safety monitoring was carried out. With enrollment recorded as 1 and no subject data analyzed, the entries should not be treated as a reliable estimate of comparative safety or as evidence that an event cannot occur. Zero affected in a registry cell does not establish zero risk.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, double-blind, placebo-controlled trial intended to evaluate hydroxychloroquine as post-exposure prophylaxis in two cohorts. Its primary question concerns positive COVID-19 tests among exposed healthcare workers. The design and question are described, but the record reports enrollment of 1, early closure, and no subject data analysis. There is therefore no analyzed efficacy result in the registry record.
This means the record cannot establish whether the hydroxychloroquine and placebo groups differed in positive tests. It also cannot show the size or precision of a possible difference, because no estimate or confidence interval is reported. A missing result is not the same as a finding of no effect: no treatment contrast is reported at all. Nor can the registry entries be used to conclude that a treatment effect would be large or small.
The listed adverse-event counts offer limited descriptive information, but they do not constitute a comparative safety analysis. The counts do not include enough detail to assess event type, relationship to treatment, or rates over a defined period. The record also does not explain why the study was terminated. Neither the termination status nor the absence of analyzed data should be interpreted as a statistical conclusion about efficacy or safety.
In general, a trial’s design can make a question testable, while its analyzed results are needed to answer that question. Here, the design description establishes the intended comparison, but the registry record does not report the outcome data needed to make that comparison. The most defensible conclusion is limited to what is documented: the study was terminated, enrollment was recorded as 1, and no subject data was analyzed. Any broader claim about prevention, lack of prevention, or comparative safety would go beyond the reported results.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a planned comparison and an analyzed result. Randomization, masking, a placebo comparator, and a clearly framed endpoint describe important features of a study design. However, those features cannot substitute for outcome counts and an analysis. The record reports no subject data analysis, so no efficacy estimate can be assessed for magnitude, uncertainty, or compatibility with a null effect.
Enrollment is recorded as 1, while the record also states that the study closed early. These registry entries underscore why conclusions depend on the information actually analyzed, not just on a trial’s phase or design labels. The registry does not report group-specific enrollment, an analysis population, or an explanation for termination. It is therefore not possible to determine from the record how far the planned comparison progressed or why it did not yield an analyzed result.
The case also emphasizes the role of transparent reporting. Knowing the endpoint title and timeframe helps clarify the intended question, but definitions of testing, follow-up, missing data, and statistical analysis are needed to interpret an estimate. Those details are not reported in the registry record. The adverse-event counts likewise require context before they can support a meaningful comparison.
For clinical researchers and biostatisticians, the key lesson is not a claim about hydroxychloroquine. It is that study design, conduct, and reported analysis are distinct parts of the evidence. When outcome data and the analysis are absent, statistical methods cannot recover a treatment effect. Accurate interpretation must preserve that boundary rather than treating a terminated study as either a positive or negative efficacy result.
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 principal limitation is that the registry record states no subject data was analyzed. Although enrollment is recorded as 1, no primary-outcome counts, group-specific percentages, or treatment-effect estimates are reported. The record therefore cannot support an efficacy comparison. It also does not identify the cohort or treatment arm associated with the recorded enrollment.
The study was terminated, but the reason for termination is not reported in the registry record. The record gives a primary completion date of 2021-06-04, but does not explain how that date relates to the early closure. It does not report recruitment progress, deviations from the intended design, or whether any participant completed follow-up.
Important endpoint details are absent. The registry record does not define the COVID-19 testing procedure, specify the timing of testing in relation to exposure, or give the denominator for the stated percentage. The timeframe says that outcome 1 will be analyzed at enrollment completion, but does not provide a follow-up schedule. The other listed outcome measure is not described in the record details.
The record does not report dose, schedule, or duration for hydroxychloroquine, nor does it explain the role of the listed Vitamin D intervention. It also lacks a statistical analysis plan, sample-size justification, analysis populations, missing-data methods, or multiplicity strategy. These gaps preclude evaluation of the intended analysis and limit interpretation of the adverse-event counts, whose definitions and event details are not given. The limitations are about the available record; they do not establish why the study ended or what an unreported analysis might have shown.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Hydroxychloroquine as Post-Exposure Prophylaxis Against COVID-19 Infection — NCT04372017.
- Registry record last updated 2021-12-10; status last verified 2021-12.
- Results first posted 2021-12-10.
- 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
NCT04372017 is a phase 3 randomized, double-blind, placebo-controlled, parallel study sponsored by Sanford Health. It planned to evaluate hydroxychloroquine for post-exposure prevention of COVID-19 in healthcare workers and high-risk participants. The primary outcome concerns positive COVID-19 tests among exposed healthcare workers treated with hydroxychloroquine. The registry lists Vitamin D as an intervention but does not describe its role.
The study is recorded as terminated, with enrollment of 1. The primary outcome description states that no subject data was analyzed and that the study was closed early. No efficacy comparison, effect estimate, confidence interval, or p-value is reported. Adverse-event entries list limited counts by group, with no deaths recorded. The registry record does not explain termination or provide the analysis and endpoint details needed for further interpretation.