Prophylactic Ivermectin in COVID-19 Contacts: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prophylactic Ivermectin in COVID-19 Contacts (NCT04422561), a randomized phase 2, phase 3 study. The primary outcome is Development of Symptoms ( Fever ,Cough, Sore Throat, Myalgia,Diarrhea, Shortness of Breath).

2. Clinical Question

This is a question about a comparison between assigned groups in the population enrolled in the trial. It is not, by itself, a question about all possible contacts or about outcomes beyond the registry’s stated follow-up. The posted primary outcome concerns symptoms; the record lists development of COVID as a secondary outcome, but the endpoint results and analysis details for that outcome are not reported in the registry record. The result should therefore be read as a comparison of the recorded primary symptom counts, not as a complete account of every clinical outcome that might matter.

3. Trial Design

The registry identifies NCT04422561 as a completed randomized trial with phase listed as PHASE2 and PHASE3. Its title concerns prophylactic ivermectin in COVID-19 contacts, and its official title specifies asymptomatic family close contacts of a patient with COVID-19. Zagazig University is listed as the sponsor. The record gives an enrollment of 340 and identifies COVID as the condition.

The design is recorded as sequential, and masking is listed as none. Thus the registry describes randomized allocation without masking. It does not report how the random sequence was generated, how allocation was concealed, or the details of the sequential design. Those features should not be inferred from the labels alone. The ivermectin group received prophylactic ivermectin tablets; the control group was to be observed without prophylaxis.

The record gives a study start date of 2020-05-31 and a primary completion date of 2020-07-14, with status COMPLETED. The brief summary describes follow-up for 14 days for symptoms and diagnosis of COVID-19. The primary outcome timeframe is stated as within 14 days after enrollement, using the registry’s spelling. The primary measure is a count of participants with symptoms. Development of COVID is listed as a secondary outcome, and the record reports two outcome measures overall.

The outcome counts identify 203.0 participants in the ivermectin group and 101.0 in the control group. These reported group denominators do not match the registry’s overall enrollment figure, and the reason for the difference is not reported in the registry record. Participant flow, withdrawals, exclusions and the populations included in each outcome analysis are also 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

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 Development of Symptoms ( Fever ,Cough, Sore Throat, Myalgia,Diarrhea, Shortness of Breath), measured over within 14 days after enrollement.

The primary endpoint counts participants who developed the listed symptoms: fever, cough, sore throat, myalgia, diarrhea or shortness of breath. The registry describes assessment by history taking and clinical examination, and gives the timeframe as within 14 days after enrollement. The outcome type is a participant count, rather than a continuous measurement such as a laboratory value or symptom score. The record does not give a separate definition of whether one or several symptoms were required, how symptoms were verified, or whether a particular severity threshold applied.

A symptom endpoint can capture experiences that are relevant to participants and can be assessed during follow-up. In a randomized comparison, the number of participants meeting the endpoint in each group describes how often the recorded event occurred in the analyzed groups. It does not establish that every symptom was caused by the same process, nor does the count describe symptom severity, duration or impact unless those features are specifically measured. They are not reported in the registry record.

The registry separately lists development of COVID as a secondary outcome. That distinction matters: the primary endpoint is the specified symptom count, while a clinical diagnosis outcome is listed separately. The posted results described in the record give counts for the symptom endpoint; results for the secondary outcome are not reported in the registry record. Interpretation should remain tied to the endpoint and follow-up actually recorded.

7. Results Posted in the Registry

• Ivermectin Group: 7.4% (15/203) versus 58.4% (59/101) on control; risk difference -51.0 percentage points (95% CI -61.3 to -40.8), risk ratio 0.13 (0.08–0.21); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the event occurred or did not occur during the specified period. Here, the event is the primary symptom outcome recorded within 14 days after enrollement. The registry reports counts of participants with the event in each group. The proportion in each group expresses the event count relative to that group’s reported denominator. This is a direct description of the observed outcome and does not require assuming that symptom events are normally distributed.

What does the risk difference express?

The risk difference subtracts the control-group event proportion from the intervention-group event proportion, using the comparison’s stated direction. The posted estimate is -0.510, with a 95% confidence interval from -0.613 to -0.408. A value below zero means the observed event proportion was lower in the ivermectin group under this direction of comparison. The interval describes uncertainty around the estimated difference. It is not a range containing a fixed percentage of individual participant outcomes, and it does not account for unreported sources of bias or uncertainty in the trial’s conduct.

Why are risk ratio and odds ratio also reported?

The risk ratio compares the event proportions between groups, while the odds ratio compares event odds. Both express relative contrasts, but they use different scales and need not have the same numerical value. The posted risk ratio is 0.127, with a 95% confidence interval from 0.076 to 0.211. The posted odds ratio is 0.057, with a 95% confidence interval from 0.029 to 0.110. These measures are not interchangeable with the risk difference, which expresses an absolute contrast between proportions. The estimates are unadjusted.

What does the p-value add?

The unadjusted p-value is <0.001. In general, a p-value describes how incompatible the observed data are with a specified null model, assuming that model and the calculation’s assumptions apply. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Its interpretation depends on the analysis being considered. The record does not report a detailed statistical analysis plan, so the reported p-value should be read as an unadjusted comparison rather than evidence of a particular adjusted or prespecified analysis.

Randomization is intended to make treatment groups comparable on average at assignment, which supports a causal interpretation when allocation is properly implemented and follow-up and analysis preserve that comparison. The record confirms randomized allocation but does not report the sequence-generation method, allocation concealment, analysis population or handling of missing data. Masking is listed as none. Without masking, knowledge of assignment could potentially affect symptom reporting or assessment; the registry does not report procedures to assess or address that possibility. These are general considerations, not claims that any particular bias occurred in this trial.

The registry’s outcome is a count of participants with an event, so the direct comparison treats each participant’s event status as binary. The registry does not report repeated event counts or event timing analyses. The listed secondary outcome, development of COVID, is distinct from the primary symptom endpoint, and its results are not reported in the registry record. No conclusion about the secondary outcome can be drawn from the primary symptom comparison.

Confidence intervals are useful alongside p-values because they show both the direction and the precision of an estimate on its measurement scale. The reported interval for the risk difference is entirely negative, while the interval’s width also conveys uncertainty about the size of that difference. In general, confidence intervals depend on the statistical model and method used to calculate them. The method used for the posted comparisons is not reported in the registry record. Accordingly, the interval can be described as posted, but its construction cannot be independently characterized from this record.

Finally, the group denominators reported for the endpoint should be kept distinct from overall enrollment. The record gives enrollment as 340, but endpoint denominators of 203.0 and 101.0. Statistical interpretation depends on knowing who contributed data and how missing or excluded observations were treated. Those details are not reported in the registry record. The unadjusted estimates are therefore informative descriptions of posted counts, while the absence of fuller analysis documentation limits assessment of robustness.

10. Confidence Intervals and Precision

The posted risk difference is -0.510, with a 95% confidence interval from -0.613 to -0.408. This interval describes uncertainty in the estimated difference between the group event proportions under the calculation used. Its values are all negative, consistent with a lower observed symptom proportion in the ivermectin group for this comparison. The interval does not mean that the true effect has a 95% probability of falling within these particular limits; in general, a confidence interval is produced by a method that would cover the target quantity at its stated rate over repeated samples if the method’s assumptions hold.

The relative estimates have their own intervals: the risk ratio is 0.127, with a 95% confidence interval from 0.076 to 0.211, and the odds ratio is 0.057, with a 95% confidence interval from 0.029 to 0.110. These intervals describe uncertainty on different scales. They should not be read as if they were interchangeable with the risk-difference interval.

Precision is shaped by the amount of information in the data and by the statistical method. The endpoint denominators are 203.0 and 101.0, and the posted interval gives a range of plausible effect magnitudes rather than a single exact value. The method used to calculate the intervals is not reported in the registry record. The intervals also do not incorporate uncertainty from possible outcome misclassification, incomplete follow-up, or analysis decisions that are not documented. Their numerical precision should therefore be distinguished from the broader certainty of the evidence.

The p-value is <0.001, but it does not replace the confidence intervals. The p-value addresses compatibility with a null model; the intervals help show the estimated direction and range of effect sizes compatible with the data and method. Neither alone establishes the absence of bias or the relevance of the result outside the recorded study population.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculation. For this binary outcome, the entries are participants per arm, not total events. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the stated fraction of the observed effect as the effect to detect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm in the planning illustration for a design with 80% power under those assumptions. The 90% power column gives the corresponding per-arm planning number for 90% power. Power is the probability that a specified statistical procedure will reject its null hypothesis when a particular assumed effect is present, under the assumptions of the calculation. These numbers are not observed power; they are prospective planning illustrations and should not be treated as a measure of what the completed trial achieved.

The displayed scenarios use 100% of the observed effect, 75% of the observed effect and 50% of the observed effect. In the posted illustration, planning for 100% of the observed effect gives 13 participants per arm for 80% power and 16 participants per arm for 90% power; planning for 75% gives 25 and 33 participants per arm; planning for 50% gives 59 and 79 participants per arm. Smaller effects need more participants for the same target power, all else held to the stated assumptions. These values are illustrative rather than evidence that the trial was designed using those assumptions.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.584; treatment proportion p₁ = 0.074; average p̄ = 0.329.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6645 = 1.3024.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5580 = 0.4696.
4. n = (1.3024 + 0.4696)² / (-0.5103)² = 12.1, rounded up to 13 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.584158415841584                          # control proportion
p1 <- 0.0738916256157636                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4422561)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 13 (80% power), 16 (90% power)
 75% of observed effect: n per arm = 25 (80% power), 33 (90% power)
 50% of observed effect: n per arm = 59 (80% power), 79 (90% power)
power.prop.test: 12.1 
Simulated power at n = 13 per arm: 0.868 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The record lists a primary symptom outcome and identifies development of COVID as a secondary outcome. It reports two outcome measures overall and one secondary outcome, but does not report the detailed outcome hierarchy, timing of outcome specification, or a plan for managing multiple statistical comparisons. Multiplicity refers generally to the increased chance of at least one false-positive finding when several hypotheses are tested. Whether an adjustment was planned or used is not reported in the registry record. The reported p-value is therefore best described as an unadjusted comparison, not as a multiplicity-adjusted result.

The registry record reports zero analyses. It does not provide a statistical analysis plan, identify an analysis population such as intention-to-treat or per-protocol, or explain whether any covariate adjustment was used. The posted summary comparison is unadjusted. Whether it matches a prespecified analysis or a sponsor’s final analysis is not reported in the registry record. A lack of detail does not establish that an analysis decision was improper; it limits the ability to evaluate how outcomes and analysis choices were specified and carried out.

Missing-data handling is also not reported in the registry record. The outcome denominators are 203.0 for the ivermectin group and 101.0 for the control group, while overall enrollment is 340. The record does not explain why the outcome denominators differ from total enrollment, whether participants lacked endpoint data, or how any missing observations were handled. Without participant flow or missingness information, it is not possible to assess whether the analyzed participants represent all randomized participants or whether missingness could affect the comparison.

The record does not report the number of participants assigned to each group before outcome assessment, exclusions after randomization, protocol deviations, or sensitivity analyses. It also does not report whether the secondary outcome had posted results. These omissions matter because analysis-population definitions and missing-data assumptions can affect the interpretation of a randomized comparison. The numerical results remain descriptions of the posted endpoint counts, but fuller assessment requires information absent from the registry record.

14. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures are zero in the ivermectin group and zero in the control group. The death counts are also zero in both groups. These are reported counts for the groups at risk: 203 in the ivermectin group and 101 in the control group. The record lists no serious adverse event terms.

Other adverse events are reported for the ivermectin group, with 11 affected participants among 203 at risk, and zero affected participants among 101 at risk in the control group. The registry record does not define the categories used for these other events, provide event descriptions, or report their timing, severity or relationship to the intervention. The figures are participant counts, not a detailed account of every event or its clinical course.

Zero posted serious events or deaths means none were recorded in these registry fields; it does not prove that no event could occur or that every possible event was captured. The record does not describe safety monitoring procedures, reporting completeness or follow-up for adverse events beyond the stated study period. The counts should be interpreted as the safety information posted, rather than as a comprehensive evaluation of safety.

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

The registry’s primary endpoint counts participants with specified symptoms during the stated 14-day follow-up. The posted counts and unadjusted comparisons show a lower observed symptom proportion in the ivermectin group than in the observation-only control group. The estimated risk difference is -0.510, with a 95% confidence interval from -0.613 to -0.408, and the unadjusted p-value is <0.001. These statistics describe the comparison in the posted endpoint data.

They do not, on their own, establish that the observed difference was caused by the intervention. Randomized allocation can support causal inference, but an assessment also depends on how randomization was implemented, how outcomes were assessed, who was included in the analysis, and how missing data were handled. The registry identifies the trial as randomized and unmasked but does not report key details about allocation procedures, participant flow or analysis methods. The posted result should therefore be interpreted with those documentation limits in mind.

The primary outcome is symptom occurrence, not a comprehensive measure of disease severity, duration, or all health outcomes. Development of COVID is listed as a secondary outcome, but results for that outcome are not reported in the registry record. The symptom comparison should not be substituted for the unreported secondary outcome, and the record does not support claims about outcomes outside its stated measures and follow-up.

These findings also do not automatically apply to people or circumstances beyond the trial population described in the record: asymptomatic family close contacts of a confirmed COVID-19 patient. Further participant characteristics are not reported in the registry record. The registry does not provide details of ivermectin dosing or administration, which prevents a more specific description of the tested regimen.

In general, a statistically small p-value is not a guarantee of freedom from bias, and a confidence interval does not capture every source of uncertainty. The result is best understood as a substantial observed difference in the recorded symptom endpoint, accompanied by an interval that indicates statistical uncertainty, within a record that leaves important design and analysis details undocumented. It should not be translated into medical advice or a universal conclusion about treatment.

16. Why This Trial Matters Statistically

This trial illustrates why effect estimates, denominators and uncertainty should be read together. The group symptom counts differ, but the groups also have different reported endpoint denominators. Proportions and comparative measures place those counts on a common scale, while the confidence intervals show uncertainty around the estimates. Looking only at the event counts or the p-value would omit important information about the comparison.

It also illustrates the value of distinguishing an absolute measure from relative measures. The risk difference expresses the group contrast in proportions, whereas the risk ratio and odds ratio express relative contrasts on different scales. Reporting more than one measure can help readers understand the result, provided the measures are interpreted correctly and not treated as independent findings. All posted comparisons are unadjusted.

The registry record also highlights that design labels and outcome numbers do not replace methodological detail. Randomized allocation is recorded, but the allocation procedure, analysis population, missing-data handling and statistical plan are not reported in the registry record. Masking is listed as none, which is relevant when the primary endpoint involves symptoms assessed through history taking and clinical examination. These observations identify questions for statistical appraisal; they do not establish that bias occurred.

Finally, planning illustrations derived from the observed effect can help explain how assumptions about target effect and power affect planning numbers. They are not the original trial justification and not observed power. Keeping those purposes separate prevents retrospective planning calculations from being mistaken for a design decision or a performance assessment. Together, these points make the record useful for examining how a binary clinical endpoint, comparative estimates, precision and incomplete analysis documentation fit into trial interpretation.

17. 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.

Several trial-specific details needed to assess the results are not reported in the registry record. Although the study is identified as randomized, the method used to generate the sequence and conceal allocation is not described. The design is labeled sequential, but the meaning and operational details of that design are not given. Masking is listed as none; the record does not describe safeguards for symptom assessment or reporting.

The intervention is described as ivermectin tablets, but dose, dosing schedule and duration are not reported in the registry record. The record describes asymptomatic family close contacts but does not provide fuller eligibility criteria or participant characteristics. These omissions limit the ability to judge how closely the trial participants and intervention correspond to other populations and treatment regimens.

The registry gives overall enrollment as 340, while the primary endpoint denominators are 203.0 and 101.0. It does not explain this difference, provide participant flow, or state how missing outcome data and post-randomization exclusions were handled. The analysis population and detailed statistical plan are also not reported in the registry record. These gaps restrict assessment of whether the posted comparison includes all randomized participants and whether analysis choices were prespecified.

The primary symptom outcome is described by a list of symptoms and assessment through history taking and clinical examination, but operational details of the endpoint are not reported. The registry lists development of COVID as a secondary outcome, but its results are not reported in the registry record. Safety information includes posted event counts but lacks definitions and fuller event descriptions. Finally, the unadjusted comparisons and planning illustrations do not substitute for a fully documented sponsor analysis or the trial’s original design justification.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Prophylactic Ivermectin in COVID-19 Contacts — NCT04422561.
• Registry record last updated 2020-08-27; status last verified 2020-08.
• Results first posted 2020-08-27.
• 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.

21. Record Summary

NCT04422561 is a completed randomized, unmasked trial listed as PHASE2 and PHASE3, sponsored by Zagazig University. It studied prophylactic ivermectin tablets in asymptomatic family close contacts of a person with confirmed COVID-19, compared with observation without prophylaxis. The registry reports enrollment of 340, with study dates from 2020-05-31 to 2020-07-14.

The primary outcome counts participants with specified symptoms within 14 days after enrollement. The posted counts are 15.0 in the ivermectin group and 59.0 in the control group, with endpoint denominators of 203.0 and 101.0. The unadjusted risk difference is -0.510, with a 95% confidence interval from -0.613 to -0.408; the unadjusted p-value is <0.001. Development of COVID is listed as a secondary outcome, but its results are not reported in the registry record.

Serious adverse event counts and deaths are zero in both groups; other adverse events are reported for 11 participants in the ivermectin group and zero in the control group. Important details about allocation procedures, missing data, analysis populations and the statistical plan are not reported in the registry record.