Therapeutic Plasma Exchange Followed by Convalescent Plasma Transfusion in Severe and Critically Ill COVID-19 Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Therapeutic Plasma Exchange Followed by Convalescent Plasma Transfusion in Severe and Critically Ill COVID-19 Patients (NCT04973488), a non-randomized na study. The primary outcome is Survival.

2. Clinical Question

3. Trial Design

The registry describes a parallel, non-randomized study with double masking and phase listed as NA. It records enrollment of 38 and a completed status. The listed start date is 2020-07-25, and the primary completion date is 2021-01-10. These are registry entries; they do not establish that every participant completed follow-up or that all outcomes were reported.

The treatment arm received therapeutic plasma exchange in the first 24 hours after admission to the intensive care unit, followed by convalescent plasma from donors who had COVID-19. The control arm received standard COVID-19 treatment. The registry does not describe the contents of standard treatment, the convalescent plasma product, or other treatment procedures.

Because allocation was non-randomized, the arms should not be treated as if they were formed by random assignment. Differences in patient characteristics, illness severity, clinical decisions, or other factors could influence which care a participant received and could also relate to survival. The registry record does not report enough information to determine whether such differences were measured or adjusted for. The double-masked designation is recorded, but who was masked and how masking was maintained are not reported in the registry record.

The registry identifies survival as the primary outcome and lists P/F Ratio, C Reactive Protein (CRP), Lactate Dehydrogenase (LDH), and Ferritin among the secondary outcomes. The timing and analysis details for those secondary outcomes are not reported in the registry record. No detailed statistical analysis plan or analysis results are reported.

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: All patients included in the study were adults (\>18 years) who presented with acute respiratory failure and ARDS, had positive reverse transcriptase-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 virus and presented with clinical and/or radiological signs of COVID-19 pneumonia upon hospital admission. Exclusion criteria were represented by any of the following: Pregnancy, patients with suspected or confirmed pulmonary embolisms and patients with terminal disease.

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 Survival, measured over 30 day period.

The primary endpoint is the number of participants who survived during a 30 day period. Survival is a binary outcome at the participant level: for the stated period, a participant is counted according to whether survival was recorded. The endpoint description does not provide a survival count for either arm, and the registry record does not report the result of the primary comparison.

As a general statistical rationale, survival is a clinically important outcome in a study of severe illness because it directly describes whether participants remained alive over the defined observation period. A count alone, however, is not enough to assess the precision of a comparison. Interpretation also depends on the number of participants observed in each arm, completeness and timing of follow-up, the method used to handle missing outcome status, and the statistical estimate with its uncertainty. The registry record does not report these details for the primary survival outcome.

The adverse-event data list deaths by arm, but those figures do not by themselves establish the registered primary endpoint result. The adverse-event record does not state that its death counts correspond to survival status during the primary endpoint's 30 day period. The timing and analysis population for those death counts are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods connect the way a study is organized to the conclusions that can be drawn from its outcomes. For this study, the registry describes a parallel comparison, non-randomized allocation, double masking, and a binary primary outcome: the number of participants who survived during a 30 day period. It does not report the analysis method used for that outcome or provide a numerical comparison.

What does non-randomized allocation mean?

General explanation: random allocation is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. When allocation is non-randomized, treatment assignment can be related to clinical features, care decisions, or other factors. Those factors may also be associated with survival. A difference between groups can therefore reflect both treatment and differences in the people receiving each care approach. Statistical adjustment may address measured factors under appropriate assumptions, but it cannot guarantee control of unmeasured differences.

The registry labels allocation as non-randomized. It does not report how treatment assignment was decided, which baseline variables were collected, whether adjustment was undertaken, or which analysis was used. The extent of confounding control is therefore not reported in the registry record. The double-masked label is recorded, but masking procedures and the roles of masked individuals are not reported.

How is a binary outcome compared?

General explanation: a binary outcome records whether a participant meets a defined condition, such as survival during a specified period. A comparison can be expressed using a difference in proportions, a ratio of proportions, or another suitable measure. Each estimate should be accompanied by an indication of uncertainty, such as a confidence interval. A confidence interval describes the range of values compatible with the data and the method's assumptions; it is not a guarantee that the true value lies within that range.

The registry identifies a participant count as the survival endpoint, but does not report the arm-specific survival counts, an effect estimate, a confidence interval, or a p-value. Without those results, neither the magnitude nor the statistical precision of the primary comparison can be evaluated. The death counts in the adverse-event data are not identified as the primary endpoint analysis and have no reported connection to the endpoint's 30 day observation period.

What does a planning calculation represent?

General explanation: a sample-size planning calculation estimates how many participants might be needed under specified assumptions to detect a chosen effect with a stated statistical procedure. Such a calculation is not an observed result and does not show the power achieved by a completed study. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. The registry record does not report its own design justification, and the survival effect needed to interpret any planning illustration is not reported in the registry results.

Planning based on an observed effect can be unstable, particularly when the observed estimate is uncertain. A smaller assumed effect generally requires more information to detect than a larger assumed effect, all else equal; this is a general statistical principle, not a reported result for this study. Planning figures cannot repair limitations from non-random allocation, missing outcome reporting, or incomplete information about follow-up.

Why do analysis populations and missing outcomes matter?

General explanation: an analysis population defines which participants contribute to an estimate. For example, a protocol might specify that all assigned participants are analyzed according to their original group, or it might use another population. Missing outcome information can affect estimates if the likelihood of missingness differs by group or relates to prognosis. Appropriate methods depend on the study design, the amount and pattern of missingness, and assumptions about why data are missing.

The registry record does not report the analysis population for survival, the amount of missing outcome information, or methods for handling missing data. It also does not report whether participants who did not complete follow-up were included in an analysis. These omissions limit assessment of whether the posted outcome, if reported elsewhere, would represent all enrolled participants or a selected subset.

How should multiple outcomes be considered?

General explanation: when several outcomes or statistical tests are examined, the chance of finding at least one apparently unusual result can increase. A prespecified hierarchy or multiplicity adjustment can help define how such results are interpreted. The registry names survival as the primary outcome and lists P/F Ratio, C Reactive Protein (CRP), Lactate Dehydrogenase (LDH), and Ferritin as secondary outcomes. The registry record does not report a multiplicity strategy, a detailed statistical plan, or analysis results for these outcomes.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment Arm", "Control Arm")
n      <- c(19, 19)
events <- c(9, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment Arm  19  9  47.4  24.4  71.1  27.3  68.3  27.2  68.5
ARM  Control Arm  19  5  26.3  9.1  51.2  11.8  48.8  11.9  49.1

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies survival during a 30 day period as the primary outcome and lists P/F Ratio, C Reactive Protein (CRP), Lactate Dehydrogenase (LDH), and Ferritin as secondary outcomes. It records five outcome measures, but detailed outcome definitions and analysis results are not reported for the named secondary measures. The registry record does not describe a hierarchy for testing outcomes or a method for addressing multiplicity. General statistical reasoning is that interpreting several tests without a prespecified strategy can make isolated findings harder to assess.

Missing-data methods are not reported in the registry record. The record does not state whether primary outcome status was available for all participants, how loss to follow-up was handled, or whether any missing measurements were imputed or excluded. These details matter because the completeness and pattern of missingness can affect the interpretation of an estimate.

The analysis populations are also not reported. It is not stated which participants would be included in the primary analysis, how group membership would be handled, or whether all enrolled participants contributed to each outcome. The registry lists 38 participants as enrolled, but does not provide primary endpoint analysis counts or identify how that enrollment relates to the outcome data. No statistical analyses are reported in the registry record, so the handling of multiplicity, missing data, and analysis populations cannot be checked against results.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: anaphylactic reaction (5.3%).

The adverse-event record lists 19 participants at risk for serious adverse events in each arm. In the treatment arm, 1 participant is recorded as affected by a serious anaphylactic reaction, listed at 5.3%; the control arm has 0 participants affected by that term. The record lists 0 participants affected by other serious events in either arm. It also records deaths of 10 in the treatment arm and 14 in the control arm.

These are descriptive registry counts. The record does not report event timing, duration, severity criteria, relatedness assessments, or whether individuals experienced more than one event. It does not explain the observation period for the adverse-event counts. The death counts should not be assumed to be the primary survival results, because the registry does not state that they correspond to survival during the 30 day period. Counts alone do not establish that treatment caused or prevented an event, and they do not account for possible differences between the non-randomized arms.

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

The registry record establishes that the study set out to compare early therapeutic plasma exchange followed by convalescent plasma with standard COVID-19 treatment in severe and critically ill patients. It identifies survival during a 30 day period as the primary outcome and describes a non-randomized, parallel design. It also records selected serious adverse-event counts and deaths.

The posted information does not report the primary survival result by arm, an estimated treatment contrast, or uncertainty around that contrast. It therefore does not establish the direction, size, or precision of a survival association. The death counts in the adverse-event record cannot fill this gap because their timing and relationship to the registered survival endpoint are not reported.

The study's non-randomized allocation also limits causal interpretation. General statistical reasoning is that differences in patient characteristics or care decisions can contribute to observed outcome differences when treatment is not randomly assigned. The registry does not report baseline comparisons or an adjusted analysis that would allow readers to assess this issue. Double masking is recorded, but procedural details are not available in the registry record.

The reported safety figures describe events recorded in the registry; they do not prove that the intervention caused an event or that the absence of a recorded event means there was no risk. The record does not describe event ascertainment or follow-up in enough detail to draw stronger conclusions. Overall, the available information supports a description of the trial's design and reported safety counts, not a conclusion about comparative survival or treatment efficacy.

14. Why This Trial Matters Statistically

This trial is statistically important because its stated question concerns survival in a severely ill population, while its allocation was non-randomized. That combination makes careful interpretation of the comparison especially important: differences in outcomes may be associated with treatment, but may also reflect differences between the people who received each approach. The registry record does not provide the baseline or adjusted analyses needed to assess that possibility.

The record also illustrates why a clearly named endpoint is not the same as a reported result. Survival during a 30 day period is specified as the primary outcome, but arm-specific survival counts and an effect estimate are not reported. Without those results, readers cannot assess the magnitude or precision of the primary comparison. The adverse-event death counts are not explicitly tied to the primary endpoint timeframe.

Another statistical consideration is the distinction between outcome reporting and safety reporting. A serious-event count can describe what the registry recorded, but it does not by itself show causation or provide a complete account of risk. Timing, event definitions, ascertainment, and analysis populations all affect interpretation. Those details are not reported for the safety figures.

Finally, the registry lists secondary measures alongside the primary outcome but does not report analyses or a multiplicity strategy. This matters because secondary findings can be sensitive to how outcomes and statistical tests were selected and interpreted. The record's limitations make transparent reporting of outcome results and methods particularly important for evaluating the evidence.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the primary survival counts by arm, an effect estimate, confidence interval, or p-value. It therefore does not allow a direct statistical assessment of the registered primary outcome. The adverse-event death counts are not tied in the record to the 30 day survival period, so they cannot be treated as a substitute for that endpoint.

Allocation was non-randomized. The registry does not report the allocation process, baseline characteristics, prognostic balance, or any adjustment for potential confounding. The double-masked designation lacks details about who was masked and how masking was implemented. The comparator is described only as standard COVID-19 treatment; its components are not reported.

Further limitations include the absence of reported analysis populations, missing-data methods, and a detailed statistical analysis plan. The timing and analysis details for secondary outcomes are not reported. No multiplicity approach is described. For adverse events, the registry provides selected counts but does not report event timing, relatedness, ascertainment procedures, or a detailed account of the observation period. The registry's completed status does not itself demonstrate that all outcome data or follow-up details were reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Therapeutic Plasma Exchange Followed by Convalescent Plasma Transfusion in Severe and Critically Ill COVID-19 Patients — NCT04973488.
• Registry record last updated 2024-08-26; status last verified 2024-08.
• Results first posted 2024-08-26.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, parallel, non-randomized, double-masked study with enrollment of 38 and phase listed as NA. The treatment approach was therapeutic plasma exchange in the first 24 hours after intensive care unit admission, followed by convalescent plasma; the control arm received standard COVID-19 treatment.

The primary outcome was the number of participants who survived during a 30 day period. The primary outcome result and its statistical analysis are not reported in the registry record. The adverse-event record lists 19 participants at risk for serious events in each arm, a serious anaphylactic reaction at 5.3% with 1 affected participant in the treatment arm, and deaths of 10 in the treatment arm and 14 in the control arm. These safety counts are descriptive and are not identified as the primary survival analysis.