Study of Intravenous Ampion in Adult COVID-19 Patients Requiring Supplemental Oxygen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Intravenous Ampion in Adult COVID-19 Patients Requiring Supplemental Oxygen (NCT04839965), a randomized phase 2 study. The primary outcome is Number of Participants With Occurrence of Mechanical Ventilation or Death.

2. Clinical Question

The clinical question was whether intravenous Ampion, compared with intravenous placebo, affected the occurrence of mechanical ventilation or death among adults with COVID-19 who required supplemental oxygen. The registry identifies the primary outcome population as the Intent to Treat (ITT) population and sets the assessment at Day 28. The outcome counts participants with either event; it does not report separate primary results for mechanical ventilation and death.

This is a question about a combined clinical outcome, not about either component considered alone. A participant meeting either component contributes to the count, so the combined result cannot show how many events were mechanical ventilation, how many were deaths, or whether the pattern differed by component. Separate component results are not reported in the registry record.

The posted comparison is based on 21 participants in the IV Ampion arm and 15 in the IV Placebo arm. The observed outcome count is 5 in each arm. The registry reports a risk-difference estimate of -0.095 for IV Ampion relative to placebo, with a confidence interval extending from -0.395 to 0.205. The interval spans both negative and positive values, so the estimate does not precisely determine the direction or size of the difference.

3. Trial Design

The registry describes a Phase II randomized, double-blinded, parallel-group study with placebo control. The official title identifies it as a safety and efficacy study of IV Ampion in adult COVID-19 patients requiring oxygen supplementation. The brief description likewise states that the trial was intended to evaluate safety and the clinical course and outcomes in adults requiring supplemental oxygen.

The listed interventions are Ampion, identified as a biological intervention, and saline, identified as another intervention. The arm descriptions specify IV Ampion and IV placebo, each administered by intravenous infusion. The registry does not report a dose, infusion schedule, treatment duration, or additional details of care alongside the study interventions.

Enrollment is reported as 36. The posted arm counts are 21 for IV Ampion and 15 for IV Placebo. These are the participant counts attached to the posted primary outcome. The registry identifies the primary outcome population as Intent to Treat (ITT), but does not give a fuller description of how that population was defined or handled in the analysis.

The study started on 2021-07-05, and primary completion is listed as 2022-02-07. Its status is TERMINATED. The reason for termination, whether recruitment or follow-up ended as originally intended, and any changes to the planned trial are not reported in the registry record. Randomization and double masking are recorded, but the method of sequence generation, allocation concealment, and the people included in the masking are not specified.

The primary outcome was occurrence of mechanical ventilation or death by Day 28. One secondary outcome is posted: the number of participants with treatment-emergent adverse events of Ampion compared with placebo. The record lists 2 outcome measures and no analysis entries. It does not provide the original statistical design assumptions or a sample-size justification.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT)

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 Occurrence of Mechanical Ventilation or Death, measured over Day 28.

The primary endpoint counts participants with occurrence of mechanical ventilation or death by Day 28. It is a binary participant-level outcome: each participant either had at least one of the specified events by the assessment time or did not. The registry describes the measure as the number of participants and identifies the analysis population as Intent to Treat (ITT).

A combined outcome can capture whether participants experienced a serious deterioration, while using one overall endpoint for the comparison. Its interpretation is limited by the combination: a count for the composite does not show how often each component occurred separately. The registry record does not report separate counts for mechanical ventilation and death within the primary outcome, nor does it describe whether one component was more common or drove the combined result.

Day 28 defines the time point for assessing the outcome. The endpoint therefore concerns whether the event occurred by that time, rather than the time until the event. The posted result gives 5 participants with the outcome in each arm, with arm sizes of 21 for IV Ampion and 15 for IV Placebo. The registry does not give additional detail on outcome adjudication, event definitions beyond the description, or how participants with incomplete outcome follow-up were treated.

7. Results Posted in the Registry

• IV Ampion: 23.8% (5/21) versus 33.3% (5/15) on control; risk difference -9.5 percentage points (95% CI -39.5 to 20.5), risk ratio 0.71 (0.25–2.04); unadjusted two-proportion z-test p = 0.529.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: it records whether mechanical ventilation or death occurred by Day 28. For a binary outcome, an analysis can compare the event proportion in each group using measures such as a risk difference, risk ratio, or odds ratio. These measures express the group contrast in different ways, and none changes the underlying observed event counts.

What does the risk difference express?

The reported risk difference is -0.095 for IV Ampion relative to IV Placebo. A risk difference subtracts the comparator group’s event proportion from the intervention group’s event proportion. A negative estimate indicates that the observed proportion was lower in the intervention group for this comparison; it does not establish that the difference is a true or reproducible effect. The listed proportions are 0.238 for IV Ampion and 0.333 for placebo. The confidence interval for the risk difference is -0.395 to 0.205, which includes zero and ranges across both directions of difference.

How do relative measures differ?

The risk ratio compares the event proportion in one group with the proportion in the other. The posted risk ratio is 0.714, and its confidence interval is 0.251 to 2.036. The odds ratio compares the odds of the event between groups; the posted odds ratio is 0.625, with a confidence interval of 0.144 to 2.718. A ratio value representing no relative difference is 1, while the corresponding no-difference value for a risk difference is zero. Both relative-measure intervals extend across their no-difference value. Because these are different summaries of the same data, they should be interpreted together with the counts and precision, not as separate trials of the hypothesis.

What does the p-value contribute?

The reported unadjusted p-value is 0.529. In general, a p-value describes how unusual data at least this discrepant would be under a specified null hypothesis and statistical model. It does not provide the probability that the treatment has no effect, and it is not a measure of effect size. The word unadjusted indicates that this reported value is not adjusted for multiplicity. The registry record does not report whether an adjusted analysis was planned or performed.

The p-value and confidence interval answer related but different questions. The p-value summarizes compatibility with a null model under its assumptions, while the interval communicates uncertainty around an effect estimate. Neither replaces attention to the arm sizes, event counts, outcome definition, or study conduct. In this trial, the limited number of participants and the broad intervals are central to interpretation.

Why can sparse binary data be uncertain?

General statistical explanation: when a binary outcome has few observed events, the estimate can be sensitive to individual observations. In a small trial, an additional event or a different outcome classification could noticeably change a group proportion and its contrast. This is one reason estimates from small samples commonly have broad uncertainty intervals. The posted primary results contain 5 events in each group, with 21 and 15 participants in the respective arms.

The reported intervals and p-value come from an analysis of the observed participant data, but the registry record does not identify every computational detail needed to reproduce the methods. The statistical model, confidence-interval construction, exact test or approximation, covariate adjustment, and handling of missing outcomes are not reported in the registry record. The posted results should therefore be described using the stated estimates rather than attributing an unreported method to the analysis.

What is not known about the analysis plan?

The registry identifies the primary outcome as an ITT measure, but does not explain the exact ITT definition or whether all randomized participants were included in the analysis. It does not report a prespecified analysis plan, a hierarchy among outcomes, planned subgroup analyses, interim analyses, or a sample-size justification. There are no analysis entries in the record. A lack of posted analysis detail is not evidence that a particular procedure was or was not used; it means that procedure cannot be described from the registry record.

The secondary outcome concerns treatment-emergent adverse events, and the record lists one secondary outcome among 2 outcome measures. The methods used to summarize or compare this outcome are not reported. The primary comparison is unadjusted as posted. No recalculation is needed to state the estimates in the record, and no additional causal or adjusted interpretation can be inferred from them.

For binary outcomes, risk differences are often straightforward to interpret in absolute terms, while ratios describe relative contrasts. General statistical explanation: the choice of measure should be guided by the scientific question, and a measure should not be selected after looking at which gives the most favorable impression. Because the original analysis plan is not reported, the registry record does not establish why these particular comparative measures were selected or whether they were specified in advance.

10. Confidence Intervals and Precision

The main precision feature of the primary result is the breadth of its confidence interval. The risk-difference estimate is -0.095, and its interval extends from -0.395 to 0.205. It includes zero, which is the value corresponding to no absolute difference between the groups, and it extends to estimates on either side. The data therefore leave substantial uncertainty about both the direction and the size of the risk difference.

For general interpretation, a confidence interval is a range generated by a statistical procedure that, under its assumptions, reflects uncertainty in the estimate. It is not a guarantee that the true value lies within this particular interval, nor does it mean that every value in the range is equally plausible. The interval’s width matters: a point estimate alone can look more definitive than the data justify.

The relative-effect intervals are also broad. The risk ratio is 0.714, with an interval from 0.251 to 2.036; the odds ratio is 0.625, with an interval from 0.144 to 2.718. Each interval includes the relative no-difference value of 1. Together with the risk-difference interval, these results show that the posted data do not narrowly constrain the comparison.

There are 21 participants in the IV Ampion arm and 15 in the IV Placebo arm, with 5 primary events in each. Such a small set of observations provides limited information for estimating a group difference. The registry does not report a separate precision analysis or additional details about the method used to construct the intervals. Precision should be understood from the posted intervals themselves, without treating the point estimates as exact or the interval as evidence of equivalence.

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 planning figures are illustrations based on the observed effect, not the trial’s own original design assumptions. For this binary outcome, the reported figures are participants per arm. They are not total event counts. The calculation 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 rows describe planning for 100%, 75%, and 50% of the observed effect. At 100% of the observed effect, the illustration gives 353 participants per arm for 80% power and 471 participants per arm for 90% power. At 75% of the observed effect, it gives 642 participants per arm for 80% power and 859 participants per arm for 90% power. At 50% of the observed effect, it gives 1,479 participants per arm for 80% power and 1,979 participants per arm for 90% power.

In plain terms, the 80% power column gives the number of participants per arm in a hypothetical study designed to have an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column gives the corresponding number for a 90% chance. These are planning quantities, not counts from the trial. Smaller effects require more participants to detect under the same assumptions, which is why the figures increase as the effect fraction decreases.

This is not observed power. The trial’s own original design assumptions and sample-size justification are not reported in the registry record. These figures do not establish what the trial was designed to detect, and they should not be interpreted as an explanation for its enrollment or status.

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 = 0.333; treatment proportion p₁ = 0.238; average p̄ = 0.286.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6389 = 1.2522.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6353 = 0.5347.
4. n = (1.2522 + 0.5347)² / (-0.0952)² = 352.0, rounded up to 353 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 <- 0.333333333333333                          # control proportion
p1 <- 0.238095238095238                          # 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(4839965)
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 = 353 (80% power), 471 (90% power)
 75% of observed effect: n per arm = 642 (80% power), 859 (90% power)
 50% of observed effect: n per arm = 1,479 (80% power), 1,979 (90% power)
power.prop.test: 352 
Simulated power at n = 353 per arm: 0.802 (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 registry record lists 2 outcome measures and identifies one secondary outcome: the number of participants with treatment-emergent adverse events of Ampion compared with placebo. It reports no analysis entries. The available record therefore does not provide a complete statistical analysis plan or a full account of how multiple outcomes were handled.

Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. In general, making many comparisons can increase the chance of a result that appears unusual by chance. A prespecified testing hierarchy or other adjustment may address that concern, but the registry record does not report whether such an approach was planned or used. The posted primary p-value is unadjusted, and no multiplicity-adjusted result is reported.

The primary outcome population is labeled Intent to Treat (ITT). The record does not describe the operational definition, confirm whether every randomized participant was included, or state how participants with missing Day 28 outcomes were handled. The number of participants with missing primary outcome data is not reported in the registry record. No imputation method, sensitivity analysis, or missing-data assumption is described.

The record also does not report whether interim analyses were planned or conducted, whether outcome definitions changed, or whether subgroup analyses were specified. None of these details should be inferred from the posted result or the trial’s TERMINATED status. The reason for termination is not reported in the registry record.

These gaps limit assessment of how the analysis was specified before results were known, how incomplete observations were addressed, and how the primary result fits with the other measured outcomes. They do not demonstrate that a particular bias occurred. Rather, they mark aspects of trial conduct and analysis that cannot be evaluated 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute respiratory failure (28.6%), cardiac arrest (26.7%), septic shock (20.0%), respiratory failure (14.3%), atrial fibrillation (6.7%).

The registry reports serious adverse events for 11 of 21 participants in the IV Ampion group and 8 of 15 in the IV Placebo group. It also reports other adverse events for 15 of 21 and 12 of 15 participants, respectively. Deaths are listed as 6 in each group. These are descriptive counts within the posted groups; they should not be treated as adjusted comparisons or as evidence that the groups had equivalent safety outcomes.

The registry lists Acute Respiratory Failure at 28.6%, Cardiac Arrest at 26.7%, Septic Shock at 20.0%, Respiratory Failure at 14.3%, Atrial Fibrillation at 6.7%, and Cardio Respiratory Arrest at 6.7% among the top serious-event terms. The denominator for these term percentages is not reported in the registry record. The terms may describe events rather than unique participants, and the record does not give enough detail to determine their overlap or relationship to the primary endpoint.

These figures describe reported adverse events in a small trial. They do not by themselves establish causation, comparative risk, or a complete safety profile. Further details about event timing, severity definitions, attribution, and analysis methods are not reported in the registry record.

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

The posted result describes a comparison of the occurrence of mechanical ventilation or death by Day 28 among participants assigned to IV Ampion or IV Placebo. There were 5 participants with the outcome in each group; the posted group sizes were 21 and 15. The estimated risk difference was -0.095, with a confidence interval from -0.395 to 0.205 and an unadjusted p-value of 0.529.

These data do not give a precise estimate of the difference. The interval includes no absolute difference and values on either side, while the relative-effect intervals are also broad. The point estimate alone should not be read as proof of benefit or harm. Conversely, a result that does not narrowly distinguish the groups is not proof that the interventions are equivalent. The posted sample is limited, and its estimates retain substantial uncertainty.

The combined endpoint does not show the separate frequency of mechanical ventilation and death. The registry does not report component-specific primary results, missing-data details, or the reason the study was terminated. These limitations prevent a fuller account of how the observed combined outcome arose and how representative the analyzed participants are of the intended population.

The registry also presents adverse-event counts, including serious adverse events and deaths. Those figures are descriptive and do not independently establish a causal relationship to either intervention. No clinical recommendation follows from these statistics alone. The appropriate statistical conclusion is narrower: the registry reports a small randomized comparison with equal event counts, a risk-difference estimate whose interval spans both directions, and insufficient precision to settle the size or direction of the underlying difference.

16. Why This Trial Matters Statistically

This trial illustrates why an effect estimate should be read alongside its uncertainty. The point estimate for the primary outcome is negative, but its confidence interval extends from -0.395 to 0.205. That range includes no difference and also allows differences in either direction. Focusing only on the point estimate would understate how much uncertainty remains in the comparison.

The trial also shows how equal event counts can coexist with different arm sizes. The registry reports 5 participants with the primary outcome in each arm, with 21 participants assigned to IV Ampion and 15 to IV Placebo. The risk difference and relative measures provide formal comparisons that account for the group proportions, but their wide intervals underline the limited information in the observed data.

Another statistical issue is the use of a composite endpoint. Combining mechanical ventilation and death can summarize a clinically important outcome in a single measure, but it makes the result less informative about each component. Without separate component counts, readers cannot tell which event types contributed to the total or whether their patterns differed.

Finally, the record illustrates the distinction between a trial result and a planning illustration. The displayed participant requirements are calculated from the observed effect under stated assumptions; they are not the trial’s original sample-size rationale and are not observed power. Since the original design assumptions are not reported, these calculations should be kept separate from conclusions about why enrollment was 36 or why the trial was terminated.

These features matter for researchers interpreting small clinical trials: effect size, interval width, endpoint construction, analysis transparency, and design assumptions all shape what a result can support. The registry offers useful counts and comparative estimates, but important details needed for a complete methodological assessment are not reported.

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.

The main trial-specific limitation is the modest number of participants represented in the primary result: 21 in the IV Ampion arm and 15 in the IV Placebo arm. There were 5 participants with the outcome in each group, and the confidence interval for the risk difference is broad. This limits precision and makes it difficult to determine the direction and magnitude of the underlying difference.

The primary outcome combines mechanical ventilation or death. The registry does not report separate results for those components, so the overall count cannot explain which component contributed to the observed events. Outcome ascertainment and adjudication procedures are also not described beyond the endpoint definition and Day 28 timeframe.

The record identifies an ITT population but does not explain the population definition or how missing outcomes were handled. It does not report the analysis model in enough detail to reproduce the comparison, nor does it provide a full analysis plan, multiplicity strategy, interim-analysis information, or sample-size justification. The reason for the TERMINATED status is not reported in the registry record.

Safety reporting is also limited in detail. The record provides counts for serious and other adverse events and deaths, but does not report the denominator behind the listed serious-event term percentages, event overlap, timing, or attribution methods. These limitations do not establish that the results are biased or that events were caused by an intervention; they identify information unavailable for assessment.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study of Intravenous Ampion in Adult COVID-19 Patients Requiring Supplemental Oxygen — NCT04839965.
• Registry record last updated 2022-11-30; status last verified 2022-03.
• Results first posted 2022-11-30.
• 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

The registry record describes a Phase II, randomized, double-blinded, parallel-group placebo-controlled study of IV Ampion in adults with COVID-19 requiring supplemental oxygen. Enrollment is reported as 36, and the status is TERMINATED. The listed start date is 2021-07-05, with primary completion on 2022-02-07.

The primary endpoint was the number of participants with mechanical ventilation or death by Day 28 in the ITT population. The posted counts were 5 of 21 for IV Ampion and 5 of 15 for IV Placebo. The risk difference was -0.095, with a confidence interval from -0.395 to 0.205 and an unadjusted p-value of 0.529.

One secondary outcome is listed, and the record reports no analysis entries. The original design assumptions, missing-data handling, reason for termination, and detailed analysis plan are not reported in the registry record.