Operative vs Non-Operative Management of Acute Appendicitis and Acute Cholecystitis in COVID-19 Positive Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Operative vs Non-Operative Management of Acute Appendicitis and Acute Cholecystitis in COVID-19 Positive Patients (NCT04748120), a randomized na study. The primary outcome is Number of Participants With Pulmonary Complications.

2. Clinical Question

The study hypothesis described in the registry was that patients with COVID-19 could have safe operative outcomes compared with patients managed non-operatively. That wording identifies the question the study set out to examine; it does not establish that the treatments were equivalent or that either approach was safer. The posted results contain one participant in each arm, with zero pulmonary complications recorded in each. With so few observations, the results cannot characterize the range of outcomes that might occur in a larger group of eligible patients.

The record also lists outcomes involving post-intervention intensive care admission, all-cause mortality, complications measured with the Clavien-Dindo Classification, length of hospital stay, and emergency-room visits or readmission. Numerical results for these outcomes are not reported in the registry record. The clinical question is therefore broader than the result that can be interpreted from the posted primary outcome.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. Participants were assigned to operative management or non-operative management. The operative arm is described as treatment with surgery; the non-operative arm as treatment with antibiotics. Because masking was absent, participants and clinical teams were not blinded to the assigned management strategy. The record does not report further details about the randomization sequence or how assignments were implemented.

The listed enrollment is 2. The posted primary outcome data show one participant in each arm. The trial status is terminated. The record lists a study start date of 2020-12-28 and a primary completion date of 2021-04-06. The reason for termination is not reported in the registry record, so these entries do not establish why the study ended or whether any planned recruitment target was reached.

The study addressed acute appendicitis and acute cholecystitis among patients with active mild to moderate COVID-19 infection. Its description refers to uncomplicated cases considered amenable to laparoscopic treatment. The registry record does not report the precise diagnostic criteria, the distribution of the two conditions among participants, or other baseline characteristics. It is therefore not possible to determine from the posted results whether the participants in the two arms had comparable clinical presentations.

The primary outcome was pulmonary complications up to 90 days. The definition included pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. For operative management, the description includes non-invasive or invasive ventilation, or extracorporeal membrane oxygenation, after initial extubation, as well as inability to extubate as planned. For non-operative management, it includes any intubation. The registry lists seven outcome measures in total, including the primary outcome and secondary outcomes. It records five posted secondary outcomes, but numerical findings for those outcomes are not reported in the registry record.

The registry record does not report a target sample size, a sample-size justification, detailed analysis methods, or an analysis population definition. No reason for stopping recruitment is reported. These absences limit interpretation of the trial’s intended design and of how the two posted observations relate to any original recruitment plan.

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

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 Number of Participants With Pulmonary Complications, measured over Up to 90 days.

The primary endpoint counts participants with pulmonary complications up to 90 days. It includes pneumonia and acute respiratory distress syndrome, as well as specified forms of respiratory support or failure to extubate as planned. The definition differs by assigned management: after surgery, it includes qualifying ventilation or extracorporeal membrane oxygenation following initial extubation, or inability to extubate as planned; in the non-operative arm, it includes any intubation. The registry record does not provide further detail on how events were adjudicated.

A pulmonary-complication endpoint is relevant to the question because the study concerns patients with active COVID-19 who are also being managed for acute abdominal conditions. Counting participants with an event gives a direct description of how many people in each arm experienced the defined outcome during follow-up. It does not, by itself, describe severity beyond the event definition, the timing of each event, or the cause of an event.

The posted results report zero participants with pulmonary complications in the operative arm and zero in the non-operative arm, with one participant in each. These counts describe the observed participants only. They do not show that the underlying risk is zero in either group. With only one participant per arm, a single additional event would materially change the observed pattern, and the record provides no confidence intervals or other uncertainty estimates.

The endpoint’s follow-up window is up to 90 days. The registry record does not report individual follow-up duration, completeness of follow-up, or whether any participant was lost to follow-up. Those details matter because a participant must be observed sufficiently to determine whether the endpoint occurred during the specified period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group design. In a randomized trial, assignment is intended to make treatment groups comparable on average with respect to factors that could influence outcomes. In a parallel-group design, each participant is assigned to one management strategy and outcomes are observed under that assignment. These are general features of the design; the registry record does not describe the sequence-generation procedure, concealment of assignments, or implementation details.

What does a binary outcome count?

The primary endpoint is binary at the participant level: a participant either meets the pulmonary-complication definition during the stated follow-up or does not. The posted results express this as counts of participants with the event, rather than as continuous measurements such as a laboratory value. For the operative arm, the record reports zero events among one participant. For the non-operative arm, it also reports zero events among one participant.

Binary outcomes can be compared using measures such as a difference in event proportions, a relative measure, or a model-based estimate. These methods require an estimate to be calculated from the observed data and depend on assumptions about the data and analysis. The registry record does not report such a treatment-effect estimate for this endpoint, and its posted data are marked as not estimable for a two-arm comparison. No estimate should be inferred from the matching event counts alone.

Why is the comparison not estimable?

There is almost no outcome information available for comparing the arms: one participant is posted in each, and neither had a recorded pulmonary complication. With so few observations, the data cannot support a precise estimate of the underlying event rates or their contrast. A zero count is still an observation, but it does not imply that the event cannot occur. It indicates only that the event was not recorded among the participants represented in that arm.

In general, uncertainty is especially important when events are rare or sample sizes are small. Standard large-sample approximations can perform poorly in sparse data. Specialized exact or other small-sample methods exist, but the registry record does not report using any of them. It also does not provide confidence intervals, a p-value, or a model-based analysis for the primary outcome. The absence of those results means there is no reported inferential estimate to interpret.

What does randomization contribute?

Randomization is intended to prevent treatment choice from being determined by participant characteristics that might also affect outcome. In a sufficiently informative randomized study, this supports an interpretation of differences between arms as related to assignment, subject to adherence, follow-up, measurement, and analysis considerations. Here, randomization does not overcome the limited enrollment or produce a reliable estimate in the absence of sufficient outcome observations. The registry record does not provide enough baseline information to examine group comparability.

The trial was unmasked. In general, lack of masking can affect clinical decisions, co-interventions, reporting, and outcome assessment, depending on how outcomes are defined and collected. The registry definition includes several clinical events, but details about ascertainment and independent adjudication are not reported. The extent to which absence of masking influenced measurement cannot be determined from the registry record.

What is and is not reported about the analysis?

The registry lists no posted analyses. It does not report an analysis plan, a primary analysis population, handling of participants who did not follow assigned treatment, or adjustment for other variables. It does not report an interim-analysis plan or a multiplicity strategy. These items should not be presumed from the randomized design or from common practice in clinical trials.

In general, an analysis population specifies which participants contribute to a particular estimate. For example, an analysis may follow assigned treatment regardless of what was received, or may be restricted according to treatment received or protocol adherence. Different choices can answer different questions. Since the registry record does not state which population was used, the posted counts should be understood as the values recorded for the displayed arms, not as evidence of a particular analysis principle.

Multiplicity arises when several outcomes or comparisons are examined. In general, conducting many tests can increase the chance that at least one appears statistically notable by chance, so an analysis plan may specify how results will be interpreted. The record lists a primary outcome and secondary outcomes but does not report a multiplicity approach. Because no inferential analyses are posted, the record does not permit assessment of adjusted or unadjusted testing.

Sample-size justification is also not reported in the registry record. Without a stated target and assumptions, it is not possible to judge whether the planned enrollment was intended to detect a particular effect or how the trial’s termination related to its original plan. Any sample-size illustration based on observed effects would be a planning exercise, not observed evidence about treatment effects or trial power.

Overall, the available statistical information supports a descriptive statement about the two posted participants, but not a population-level estimate of comparative risk. Further analysis cannot substitute for outcome information that is absent from the registry record.

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("Operative Management", "Non-operative Management")
n      <- c(1, 1)
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  Operative Management  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Non-operative Management  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and secondary outcomes, but does not report a statistical analysis plan describing how multiple outcomes were to be handled. In general, multiplicity matters when researchers examine several outcomes or contrasts, because interpreting each test separately can make chance findings more likely across the collection of tests. A prespecified hierarchy, adjustment, or other strategy can clarify interpretation. No such approach is reported in the registry record.

The listed secondary outcomes include post-intervention intensive care admission, all-cause mortality, complications measured by the Clavien-Dindo Classification, median hospital stay, and emergency-room visits or readmission. The record reports five secondary outcomes as posted, but numerical results for them are not reported in the registry record. Therefore, their results cannot be assessed, and they cannot be used to qualify the primary endpoint finding.

Missing-data methods are not reported in the registry record. The record does not describe loss to follow-up, incomplete outcome ascertainment, exclusions, or the handling of missing values. It is not possible to determine whether all enrolled participants were observed through the full follow-up period or whether any planned outcomes were unavailable.

The registry record also does not define analysis populations or state whether results follow assigned treatment, treatment received, or another rule. In general, such definitions help readers understand who contributes to each estimate and how departures from assigned management are handled. No assumptions about adherence or analysis population can be made from the posted counts alone.

No interim analyses or stopping rules are reported. The trial status is terminated, but the reason for termination is not reported in the registry record. Consequently, the available information does not establish whether termination followed a planned decision, recruitment difficulty, or another circumstance. These omissions limit evaluation of both the intended analysis and the completeness of outcome reporting.

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.

The adverse-event figures list one participant at risk in each arm. In both groups, the number with a serious adverse event is zero, the number with another adverse event is zero, and deaths are zero. These are counts among the posted participants, not estimates of the frequency of harm in a broader population.

The primary endpoint separately reports zero pulmonary complications in the single participant in each arm. Although pulmonary complications and adverse events can overlap conceptually, the registry record presents them as distinct outcome fields, and it does not provide participant-level detail showing how the fields relate. The zero counts should therefore be reported as recorded rather than treated as interchangeable measures.

In general, a zero-event observation in a very small group is compatible with substantial uncertainty about the rate that might be observed in a larger group. It does not demonstrate that serious or other adverse events cannot occur. The record does not report event descriptions, timing, severity beyond the serious-event classification, attribution to treatment, or the completeness of adverse-event collection.

The registry lists complications by the Clavien-Dindo Classification as a secondary outcome, but numerical results for this outcome are not reported in the registry record. The adverse-event counts do not fill that gap. Overall, the safety figures describe no recorded events among the participants listed, while providing too little information to establish comparative safety.

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

The posted result documents zero pulmonary complications in the operative arm and zero in the non-operative arm, with one participant in each. It is a description of the observed participants. Because the registry record does not report an estimable between-arm comparison, the matching counts do not demonstrate equal risk or support a conclusion that either approach is safer.

The result also does not establish that pulmonary complications are absent among COVID-positive patients undergoing surgery or antibiotic management. No event in a very small group is not the same as proof that the event cannot occur. Without a confidence interval or other uncertainty estimate, readers cannot use the posted results to quantify how compatible the data are with different underlying risks.

The study question concerns a defined population: patients with active mild to moderate COVID-19 and uncomplicated acute appendicitis or acute cholecystitis considered suitable for laparoscopic treatment. The record does not provide detailed eligibility rules, participant characteristics, or separate results by condition. It therefore cannot establish whether the observations apply to particular clinical subgroups or to patients outside the described population.

The trial is listed as terminated, and the reason is not reported in the registry record. The available enrollment and outcome counts are consequently not enough to determine whether recruitment was complete relative to a planned target. A target sample size and its justification are not reported. These gaps also prevent an assessment of whether the study was designed to answer the comparative question with useful precision.

Secondary outcomes are listed, but their numerical results are not reported in the registry record. The primary endpoint cannot stand in for outcomes such as intensive care admission, mortality, hospital stay, or readmission. Nor do the adverse-event counts provide complete evidence about complications, since details and outcome-specific results are absent.

The appropriate interpretation is limited: no pulmonary complication was recorded for the single posted participant in either arm, while the comparative effect remains undetermined. This result neither establishes benefit nor demonstrates lack of benefit, equivalence, or harm. It is a sparse descriptive record, not a definitive resolution of the treatment question.

14. Why This Trial Matters Statistically

This trial addresses a consequential statistical challenge: comparing management strategies when the clinical population is narrowly defined and the outcome of interest may be uncommon. Randomization is a useful design feature for a comparative question, but the usefulness of the resulting estimate also depends on how much information the study collects. The registry record lists enrollment of 2, with one participant in each arm, so the posted data cannot support a precise comparison.

The example illustrates why event counts and uncertainty must be interpreted together. Seeing zero events in each arm can sound reassuring if read without context, but a count based on one participant per arm provides very little information about the range of outcomes in the wider population. Statistical interpretation should distinguish a lack of observed events from evidence that event risks are equal or negligible.

It also illustrates the importance of transparent reporting. The record describes the endpoint, follow-up window, interventions, randomization, and masked status, but does not report an estimable comparison, confidence intervals, analysis methods, analysis populations, or the reason for trial termination. Those omissions make it difficult to assess the intended inferential approach or the status of planned outcomes.

For clinical researchers, the registry entry is a reminder that a trial’s stated hypothesis and design do not themselves establish a result. A randomized label does not make an under-informative comparison conclusive. The number of participants, event definitions, follow-up completeness, and reporting of uncertainty all shape what can be learned from observed data.

The entry also highlights the value of complete outcome reporting. The registry lists secondary clinical outcomes, but their numerical results are not reported in the registry record. Without those findings, readers cannot evaluate whether the primary result aligns with other measures of clinical course or safety. The statistical lesson is straightforward: conclusions should be calibrated to the information actually available, and important uncertainty should remain explicit.

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 posted enrollment: one participant in each arm. This leaves the primary comparison not estimable and makes the observed zero counts highly limited as evidence about outcomes beyond those participants. The record does not provide an effect estimate or uncertainty interval.

The trial is listed as terminated, but the reason for termination is not reported in the registry record. A target sample size and sample-size justification are also not reported. It is therefore not possible to determine whether the posted enrollment reflects the intended recruitment target, why the trial ended, or what level of precision was originally sought.

The registry record does not report baseline participant characteristics or the distribution of appendicitis and cholecystitis across arms. The study description refers to both conditions, but separate outcome results are not available. Clinical comparability between arms and condition-specific patterns cannot be assessed.

Although the primary outcome definition and follow-up window are stated, details of outcome ascertainment, adjudication, and follow-up completeness are not reported. The record does not say whether participants were observed for the full period or whether any outcomes were missing. The effects of these unknowns cannot be evaluated.

The study was unmasked, and the registry record does not describe safeguards for outcome assessment. It does not report randomization implementation, treatment adherence, co-interventions, analysis populations, or methods for handling missing information. It also does not report interim analyses, stopping rules, or a multiplicity strategy.

Finally, numerical results for the listed secondary outcomes are not reported in the registry record. This limits assessment of outcomes beyond pulmonary complications and prevents a fuller description of clinical events. These are limitations of what can be concluded from the registry entry, not evidence that unreported outcomes were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Operative vs Non-Operative Management of Acute Appendicitis and Acute Cholecystitis in COVID-19 Positive Patients — NCT04748120.
• Registry record last updated 2022-03-14; status last verified 2022-03.
• Results first posted 2022-03-11.
• 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

The registry record describes a randomized, unmasked, parallel-group trial comparing operative management with antibiotic treatment for patients with active mild to moderate COVID-19 and acute appendicitis or acute cholecystitis. The listed enrollment is 2, and the posted primary results include one participant in each arm. The trial status is terminated.

The primary endpoint was pulmonary complications up to 90 days. The record reports zero participants with an event in each arm. It does not provide an estimable statistical comparison, confidence intervals, or a p-value. Secondary outcomes are listed, but their numerical results are not reported in the registry record.

The reason for termination, sample-size justification, detailed analysis plan, analysis populations, missing-data methods, and follow-up completeness are not reported in the registry record. The findings therefore support only a narrow descriptive statement about the participants represented in the posted results; they do not resolve the comparative treatment question.