Inhaled Ciclesonide for Outpatients With COVID19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Inhaled Ciclesonide for Outpatients With COVID19 (NCT04435795), a randomized phase 2, phase 3 study. The primary outcome is Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea.

2. Clinical Question

The clinical question is therefore about a short-term symptom status among outpatients, rather than a direct measure of viral replication or a time-to-recovery endpoint. Although the registry summary describes an aim of accelerating recovery, the primary outcome is specifically the absence of the listed symptoms at day 7. The available result addresses that defined outcome; it should not be read as a direct estimate of every aspect of recovery or as a result for hospitalized patients.

3. Trial Design

The CONTAIN study is registered as a randomized trial of ciclesonide versus placebo for mild COVID-19. The registry identifies the study as Phase 2 and Phase 3, with randomized allocation, triple masking and a factorial model. Enrollment is recorded as 215. The listed dates are a start date of 2020-09-15 and a primary completion date of 2021-06-08; the study status is terminated.

The comparison shown for the primary outcome is between the arm titled Ciclesonide Inhaled and Nasal and the Placebo arm. The active regimen combined intranasal ciclesonide with inhaled ciclesonide, while the comparator combined intranasal normal saline with a placebo inhaler. The registry record describes the active dosing as intranasal ciclesonide BID, 50mcg BID to each nostril, and inhaled ciclesonide 600mcg BID x 14 days. It describes placebo as normal saline intranasal BID and placebo 3 puff MDI inhaled BID.

The primary outcome is the count of participants with no symptoms of cough, fever or dyspnea at day 7. The registry also lists secondary outcomes concerning symptom status at day 14, overall feeling at day 7 and day 14, dyspnea, cough, hospitalization and mortality. Seven secondary outcomes are posted. No analyses are listed in the registry record, and the original protocol’s detailed analysis plan, allocation procedures, masking implementation and reasons for termination are not reported in the registry record. The factorial label is recorded, but the registry information does not explain the factorial factors or how they were incorporated into the posted comparison. Accordingly, the displayed comparison is best read as the specific ciclesonide-versus-placebo comparison shown, not as a full reconstruction of every design feature.

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.

Before assignment: Overall, 215 participants were randomised, and the modified intention-to-treat population included 203 adults with respiratory symptoms or fever.

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 Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea, measured over day 7.

The primary endpoint is the count of participants with no symptoms of cough, fever or dyspnea at day 7. It is a binary outcome at a specified follow-up time: each participant either meets the symptom-free definition or does not. The registry reports counts by arm, so the result can be understood in terms of the number meeting that definition relative to the number included in each arm’s posted outcome data.

This endpoint is used to represent a clinically interpretable state of symptom resolution across several symptoms. Looking at a fixed follow-up time makes the comparison specific: the result concerns symptom status at day 7, not how quickly participants reached that state or how symptoms changed day by day. The registry also lists symptom and overall-feeling outcomes at other times, but those are separate secondary endpoints.

The posted counts are 42 of 105 in the ciclesonide arm and 34 of 98 in the placebo arm. The corresponding posted proportions are 0.4 and 0.347. The comparison is reported as a risk difference of 0.053, with an interval from -0.080 to 0.186. These summaries describe the outcome in the participants represented by the posted data. The registry record does not report further detail about the symptom assessment instrument, the handling of missing day 7 assessments, or the analysis population definition, so the endpoint should be interpreted using the stated definition and available counts.

7. Results Posted in the Registry

• Ciclesonide Inhaled and Nasal: 40.0% (42/105) versus 34.7% (34/98) on control; risk difference 5.3 percentage points (95% CI -8.0 to 18.6), risk ratio 1.15 (0.81–1.65); unadjusted two-proportion z-test p = 0.435.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ciclesonide Inhaled and Nasal: 90.5% (95/105) versus 92.9% (91/98) on control; risk difference -2.4 percentage points (95% CI -10.0 to 5.2), risk ratio 0.97 (0.90–1.06); unadjusted two-proportion z-test p = 0.541.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ciclesonide Inhaled and Nasal and the control. The interval gives the range of effects that remain compatible with the data.

Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 7

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ciclesonide Inhaled and Nasal: 73.3% (77/105) versus 75.5% (74/98) on control; risk difference -2.2 percentage points (95% CI -14.2 to 9.8), risk ratio 0.97 (0.83–1.14); unadjusted two-proportion z-test p = 0.723.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ciclesonide Inhaled and Nasal and the control. The interval gives the range of effects that remain compatible with the data.

Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 14

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ciclesonide Inhaled and Nasal: 90.5% (95/105) versus 92.9% (91/98) on control; risk difference -2.4 percentage points (95% CI -10.0 to 5.2), risk ratio 0.97 (0.90–1.06); unadjusted two-proportion z-test p = 0.541.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ciclesonide Inhaled and Nasal and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes span symptom status, participants’ overall feeling, dyspnea, cough, hospitalization and mortality. They also include symptom-free status at day 14 and overall feeling at both day 7 and day 14. Together, these outcomes broaden the description beyond the primary day 7 symptom-free endpoint, but they represent distinct measures and follow-up times rather than interchangeable versions of one result.

The secondary comparisons should be read alongside, not instead of, the primary result. They provide additional context about the patterns recorded in the trial, but they do not resolve the uncertainty in the primary risk difference. Nor should a favorable-looking result on one secondary measure be treated as proof of an overall effect when the primary comparison remains imprecise. The registry record lists seven secondary outcomes as posted, while the count of outcome measures is eight.

Unadjusted secondary results carry less weight for confirmatory interpretation when several outcomes are assessed. Without a reported multiplicity procedure or endpoint hierarchy, the registry record does not establish which secondary findings, if any, were intended as confirmatory. Examining many outcomes can make isolated findings more likely to arise by chance. This is a general statistical concern, not a claim that any particular posted result is due to chance. The registry record also does not list analyses for these outcomes, so the displayed summaries should be understood as descriptive posted results rather than as a fully documented set of prespecified tests.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea
• Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 7
• Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 14
• Improvement in Dyspnea: Resolution of Dyspnea at Day 7
• Improvement in Cough at Day 7: Proportion of Patient With a Reduction of Cough Symptoms at Day 7
• Proportion of Participants Hospitalized for SARS-CoV-2
• Mortality

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: participants either had no cough, fever or dyspnea at day 7 or they did not. For this type of outcome, a proportion describes how common the event was within each group. The posted values are 0.4 in the ciclesonide group and 0.347 in the placebo group. A risk difference expresses the difference between those proportions on the same probability scale. Here the posted risk difference is 0.053. A positive value means the event proportion is higher in the ciclesonide arm for the stated ordering of the comparison; it does not by itself establish why the groups differed.

The interval estimate gives a range of values reasonably compatible with the observed comparison under the method’s assumptions. The reported interval for the primary risk difference runs from -0.080 to 0.186. Because this range includes zero, it includes no difference as well as differences in either direction. The registry record does not state the confidence level or the precise method used to calculate this interval. The p-value is 0.435 and is labelled unadjusted in the posted comparison. A p-value summarizes how incompatible the observed data are with a specified null model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance.

What the risk difference says

The risk difference keeps the comparison in the scale of the event proportion. This can be easier to interpret than a relative measure because it describes the separation between groups directly. The sign depends on which group is subtracted from which, so interpretation should follow the comparison as displayed. The posted estimate is positive, while its interval spans both negative and positive values. That combination indicates that the point estimate alone should not be treated as a precise account of the underlying difference.

The registry also posts relative measures for the primary outcome: a risk ratio of 1.153 with interval limits 0.805 and 1.65, and an odds ratio of 1.255 with interval limits 0.709 and 2.22. These measures answer different questions from a risk difference. A risk ratio compares event proportions as a relative quantity; an odds ratio compares event odds. Neither should be mistaken for an absolute change in the probability of the outcome. The intervals for these relative measures also include their respective null values, consistent with substantial uncertainty in this comparison.

What randomization and masking contribute

Random allocation is intended to make comparison groups similar, on average, with respect to factors that could affect the outcome. Masking is intended to reduce the influence of knowledge about assigned treatment on care, reporting or assessment. The registry classifies this study as randomized and triple masked. These design labels are useful, but the registry record does not report the specific masking roles, the allocation sequence process or the procedures used to maintain masking. The factorial model is also recorded, but the factors and their analysis are not explained in the available record. These limitations mean that the labels cannot substitute for detailed protocol information.

For a randomized comparison, the interpretation still depends on how participants and outcomes were handled after allocation. The registry record does not report the analysis population definition, the handling of missing outcomes, or whether the posted comparison follows an intention-to-treat approach. Those details matter because exclusions or missing outcome measurements can affect how well the comparison preserves the advantages of randomization.

Unadjusted comparisons and multiple outcomes

The primary comparison includes an unadjusted p-value. The registry record does not report covariate adjustment or a model specification for the posted comparison. An unadjusted comparison uses the group outcome summaries without accounting for additional participant characteristics. Such a comparison is understandable from the posted counts, but it may not match a prespecified analysis if one existed; that analysis plan is not reported in the registry record.

Several secondary outcomes are also posted. When many outcomes are examined, the chance of seeing an apparently notable result by chance can increase. Adjustment for multiple testing, a hierarchy of endpoints, or a clearly stated distinction between confirmatory and exploratory outcomes can help frame that issue. The registry record does not report a multiplicity procedure or a planned hierarchy. The secondary comparisons should therefore be read as unadjusted results, and not as independent confirmation of the primary finding.

What is not specified

The registry record does not report the original sample-size justification, the trial’s planned statistical methods, any interim analyses, the confidence level for the posted intervals, or details of missing-data handling. Those omissions prevent a full audit of whether the displayed comparison matches the intended analysis. General statistical principles can explain how the reported summaries work, but they cannot fill in undocumented protocol choices. The evidence is the posted outcome counts and comparisons, interpreted with those limitations in view.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate the possible value of the comparison. For the primary risk difference, the estimate is 0.053, and the interval runs from -0.080 to 0.186. This is a broad range that includes zero and values on either side of it. It therefore does not pin down the direction or magnitude of the underlying difference with high precision.

A confidence interval is generally a range constructed by a statistical procedure to express uncertainty about an estimate. In repeated use, the procedure has a stated coverage property under its assumptions. The confidence level and exact interval method are not reported in the registry record, so they should not be inferred. The interval endpoints themselves are posted and can be interpreted as showing the range of values compatible with the analysis, subject to its assumptions.

The posted relative estimates reinforce the uncertainty in the primary comparison. The risk ratio is 1.153, with interval limits 0.805 and 1.65; the odds ratio is 1.255, with interval limits 0.709 and 2.22. Their intervals include the respective null values of no relative difference. These measures use different scales, so they are not interchangeable with the risk difference, but all of the posted intervals indicate that the comparison is not narrowly estimated.

Precision is influenced by the amount of information in the data and by the variability of the outcome. The primary outcome denominators are 105 and 98, and the outcome is binary. Those counts provide the context for the width of the estimates, but they do not justify a claim about what a larger trial would show. The registry record does not report a target precision or a prespecified clinically important difference. As a result, the observed interval should be used to describe uncertainty, not to declare equivalence or to identify a definitive effect.

12. 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 display is a planning illustration based on the observed effect, not a record of the original trial’s design calculation. Its assumptions are a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The table reports participants per arm for 80% power and participants per arm for 90% power; these are not total sample sizes. The plotted curve visualizes the planning scenarios alongside the table, rather than adding a separate estimate of the trial’s results.

The 80% power column describes a planned sample size that, under the stated assumptions and if the chosen effect were the true effect, would give the test an 80% chance of detecting that effect using the specified significance threshold. The 90% power column uses the same idea with a higher target chance of detection. These are design concepts, not measures of how likely the observed result is to be true. The registry record’s original sample-size justification and design assumptions are not reported in the registry record.

The rows vary the effect used for planning: 100% of the observed effect, 75% of the observed effect and 50% of the observed effect. Smaller effects require more participants to detect under the same planning assumptions, which is why the illustrated sample sizes rise as the assumed effect becomes smaller. The displayed planning figures should not be confused with the enrolled number or the outcome denominators in this trial. They are prospective illustrations derived from the observed comparison and are not observed power.

13. 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 = 0.347; treatment proportion p₁ = 0.400; average p̄ = 0.373.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6841 = 1.3408.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6831 = 0.5749.
4. n = (1.3408 + 0.5749)² / (0.0531)² = 1,303.4, rounded up to 1,304 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 <- 0.346938775510204                          # control proportion
p1 <- 0.4                          # 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(4435795)
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 = 1,304 (80% power), 1,745 (90% power)
 75% of observed effect: n per arm = 2,302 (80% power), 3,080 (90% power)
 50% of observed effect: n per arm = 5,139 (80% power), 6,879 (90% power)
power.prop.test: 1303.4 
Simulated power at n = 1,304 per arm: 0.801 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and several secondary outcomes. It lists the proportion without cough, fever or dyspnea at day 7 as primary, and includes further symptom, overall-feeling, hospitalization and mortality outcomes. When a trial evaluates multiple outcomes, the interpretation of p-values depends partly on whether a testing hierarchy or multiplicity adjustment was planned. The registry record does not report such a strategy, so the secondary comparisons should not be treated as if they had a documented family-wise error control or a prespecified confirmatory order.

The record reports zero analyses in its analysis listing, while outcome results and unadjusted comparisons are posted. This means the registry information does not provide a detailed statistical analysis plan to compare with the posted results. The original sample-size justification, interim analyses, model specification, covariate adjustment plan and analysis populations are not reported in the registry record. Their absence does not prove that no plan existed; it means the record does not allow readers to verify those choices.

Missing outcome data are another unresolved issue. The study enrollment is 215, and the primary outcome denominators are 105 in the ciclesonide arm and 98 in the placebo arm. The registry record does not explain the relationship between those figures or state how missing outcomes, withdrawals or exclusions were handled. It also does not identify whether the analysis was based on all randomized participants, participants with available outcome data, or another population. These distinctions can matter for the interpretation of a randomized trial.

The registry record does not report imputation methods, sensitivity analyses for missing data, or the handling of protocol deviations. The factorial design label is present, but the record does not report the factorial factors or how their effects were modeled. These gaps limit reproducibility and assessment of robustness. They should be treated as reporting limitations rather than filled in by assumptions about common trial practice.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospithalization (5.7%), visit to the emergency department (3.1%).

The registry reports serious adverse events for 7 of 105 participants in the ciclesonide inhaled-and-nasal group and 5 of 98 participants in the placebo group. It reports other adverse events for 23 of 105 and 15 of 98 participants, respectively. Deaths are recorded as 0 in each group. These are event counts as posted; the registry record does not provide additional detail about event timing, severity grading beyond the serious classification, relatedness assessments, or how events were collected.

The top serious-event terms are displayed as Hospithalization, 5.7%, and Visit to the emergency department, 3.1%. Those labels and percentages are shown as registry terms; the record does not clarify their group-specific denominators or whether the terms overlap with other event categories. They should not be treated as additional arm-specific rates without that context.

Safety counts are descriptive and do not establish that an intervention caused or prevented an event. Differences in counts can be affected by the number observed, follow-up and reporting procedures. The registry record does not provide a detailed comparative safety analysis, confidence intervals for these counts, or an attribution analysis. The posted figures therefore describe what was recorded, while leaving uncertainty about comparative risk and event relationship.

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

The posted primary result describes the proportion of participants recorded as having no cough, fever or dyspnea at day 7 in the two trial arms. The estimate is a risk difference of 0.053, with an interval from -0.080 to 0.186 and an unadjusted p-value of 0.435. The interval includes zero and extends in both directions. These results do not provide a precise estimate of the direction or size of a difference between the groups.

This result does not establish that ciclesonide caused a higher symptom-free proportion, and it does not establish that the groups are equivalent. A non-significant p-value is not proof of no effect; the interval instead shows that the posted data leave room for a range of possible differences. Conversely, the positive point estimate is not enough by itself to establish a meaningful or reliable benefit. The registry record does not report a clinically important threshold against which to judge the size of the estimate.

The result applies to the defined endpoint, time point, comparison and participants represented in the posted data. It is not a direct measure of symptom duration, viral replication, all aspects of recovery, or outcomes in people who were hospitalized at diagnosis. The registry summary describes an outpatient population and a combined inhaled and nasal regimen. The displayed comparison does not isolate the separate contribution of inhaled and nasal treatment.

Interpretation is further limited by the absence of detailed reporting on missing outcomes, analysis populations, multiplicity, the original statistical plan and the reason the trial was terminated. The secondary outcomes add descriptive context, but their unadjusted status and the lack of a reported multiplicity approach mean they should not be used as independent proof of a treatment effect. The safety counts likewise report events observed, not causal effects. Overall, the posted results are a record of this trial’s measured outcomes and their uncertainty, rather than a definitive answer to every clinical or biological question raised by the study.

17. Why This Trial Matters Statistically

This trial illustrates why an estimate should be read together with its uncertainty. The primary point estimate is positive, but its interval includes zero and extends across values in both directions. Looking only at the point estimate would conceal how much uncertainty remains; looking only at the p-value would also miss the range and scale of values compatible with the data. The interval and the group counts give a more complete account of what the posted comparison can support.

It also shows the importance of distinguishing an endpoint from a broader research aim. The registry summary describes an aim of accelerating recovery, while the primary endpoint is the absence of specified symptoms at day 7. The endpoint is measurable and interpretable, but it answers a narrower question than recovery in every sense. Secondary outcomes can add context, yet they do not automatically broaden the primary result into a conclusion about all aspects of illness.

The record highlights the value of transparent analysis reporting. Randomization, triple masking and a factorial model are recorded design features, but the available record does not explain the analysis population, missing-data procedures, multiplicity approach or factorial modeling. These details help readers assess how the design connects to the posted estimates. Their absence limits that assessment without making the observed counts unusable.

Finally, the sample-size illustration shows how planning depends on the effect chosen for detection: smaller assumed effects require more participants under the stated assumptions. Such illustrations can help readers understand the scale of a future design, but they are not evidence that the current study was adequately or inadequately powered. The original design assumptions are not reported in the registry record. Keeping planning calculations separate from observed results is essential to a careful reading.

18. 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 limitations specific to this record constrain interpretation. The trial is marked terminated, but the reason for termination is not reported in the registry record. The record gives enrollment as 215 while the primary outcome denominators are 105 and 98; it does not explain the relationship between these figures. Without that explanation, readers cannot determine from this record whether the difference reflects missing assessments, exclusions, or another feature of the reported analysis.

The trial is labelled factorial, but the registry information does not describe the factors or explain whether the posted ciclesonide-versus-placebo comparison accounts for them. The intervention comparison combines inhaled and nasal ciclesonide, so the posted result does not separate the effects of those components. The record also does not report detailed eligibility criteria, the symptom measurement instrument, adherence, or the analysis population.

The original sample-size justification, planned statistical analysis, handling of missing outcomes, interim analyses and multiplicity strategy are not reported in the registry record. The confidence level and precise method for the posted intervals are also not specified. Seven secondary outcomes are posted, but no analyses are listed; therefore the registry record does not establish which results were planned as confirmatory or how multiple comparisons were to be interpreted.

Safety reporting is limited to posted event counts and selected serious-event terms. The record does not provide comparative safety estimates, event attribution details or fuller context for the displayed percentages. These are reporting gaps, not evidence that the omitted procedures or information did not exist. They define what can and cannot be assessed from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Inhaled Ciclesonide for Outpatients With COVID19 — NCT04435795.
• Registry record last updated 2022-06-10; status last verified 2022-05.
• Results first posted 2022-04-29.
• 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.

22. Record Summary

The registry record describes a randomized, triple-masked Phase 2 and Phase 3 factorial trial of inhaled and nasal ciclesonide versus placebo in outpatients with COVID-19. Enrollment is recorded as 215, and the trial status is terminated. Its primary endpoint is the proportion of participants with no cough, fever or dyspnea at day 7.

For that endpoint, 42 of 105 participants in the ciclesonide arm and 34 of 98 in the placebo arm met the outcome definition. The posted risk difference is 0.053, with an interval from -0.080 to 0.186 and an unadjusted p-value of 0.435. The interval includes zero and indicates uncertainty about the direction and magnitude of the comparison.

The registry posts secondary outcomes and adverse-event counts, but does not report analyses in its analysis listing. The original analysis plan, missing-data handling, multiplicity approach and reason for termination are not reported in the registry record. The results should therefore be read as posted estimates with these reporting limitations in mind.