Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS) (NCT05027815), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs).

2. Clinical Question

The clinical question is chiefly about early safety and tolerability, rather than a randomized comparison of clinical benefit. In general, a dose-limiting toxicity outcome can help characterize whether treatment-related adverse events reach a prespecified severity threshold during a specified follow-up period. It does not by itself establish whether a treatment improves respiratory status or other clinical outcomes.

The registry describes a single infusion at each dose level, but does not report the rationale for selecting the dose levels or the criteria used to move between them. The registry record reports an enrollment of 7. It does not report how many participants received each dose in the primary outcome population, or provide the observed DLT count. Those details are necessary to interpret the primary question using outcome data.

3. Trial Design

The registry lists regARDS as a Phase 1 study with non-randomized allocation, no masking, and a sequential model. Its title describes a Phase 1/2a study, while the registry phase listing is PHASE1. The intervention was cePolyTregs, described as cryopreserved ex vivo expanded polyclonal CD4+CD127lo/-CD25+ T regulatory cells, administered by intravenous infusion.

The three listed open-label arms correspond to single doses of 100 x10^6, 200 x10^6, and 400 x10^6 cells. Sequential enrollment and dose groups do not create a randomized comparison. In general, sequential dose evaluation can make dose-specific safety observations relevant to early development, but without random assignment, group differences may reflect differences in participants or care as well as dose. The registry does not report details of the sequence or rules for dose escalation.

The stated primary outcome is the number of participants experiencing DLTs during the 28 days post infusion. The registry record lists an enrollment of 7, a study start date of 2021-09-23, a primary completion date of 2022-03-02, and a status of terminated. It does not report why the study was terminated. The sponsor is Jeffrey Bluestone.

The registry lists one outcome measure and zero analyses. Although it gives the endpoint definition and follow-up period, it does not report the observed primary outcome count or a statistical comparison. Sample-size justification, an analysis plan, and any interim-analysis plan are not reported in the registry record. The design therefore supports a descriptive reading of the posted safety summaries, not a causal comparison of doses or an efficacy conclusion.

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: Of 7 participants consented, 4 met eligibility criteria and were assigned to a treatment arm. Three were enrolled in the 100x10\^6 cells arm, and one was enrolled in the 200 x 10\^6 cells arm.

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 Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs), measured over 28 days post infusion.

The primary endpoint counts participants who experienced a dose-limiting toxicity during the 28 days after infusion. The registry defines a DLT as a related treatment-emergent adverse event (TEAE) meeting both of these conditions: its NCI CTCAE 5.0 grade is 3 or higher, and it represents a worsening from the participant’s baseline clinical status by at least one grade.

This definition makes the endpoint a threshold-based safety measure. It combines event severity, change from baseline, relationship to treatment, and a specified follow-up window. In general, such a measure is useful in early-phase research because it focuses attention on adverse events considered sufficiently severe and treatment-related to meet the stated dose-limiting criteria. It is not a count of all adverse events, nor does it describe the full range of clinical outcomes.

The registry identifies the unit as participants and the parameter as a count of participants. It does not report an observed number of participants meeting the DLT definition, nor does it report a denominator for the primary outcome. The serious and other adverse-event summaries do not substitute for the DLT endpoint: those summaries are separate safety information, and the registry does not state that every event listed meets the DLT definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a participant count as the primary outcome and lists zero analyses. It does not report an inferential method, an estimate of the DLT frequency, a confidence interval, or a hypothesis test. The methods below explain how such data are generally interpreted; they are not a description of an analysis reported for regARDS.

What does a participant count represent?

A count records how many participants meet an outcome definition. For this endpoint, the definition requires a treatment-related TEAE of NCI CTCAE 5.0 grade 3 or higher, together with a worsening from baseline by at least one grade, within 28 days post infusion. A count alone does not indicate the frequency of the outcome unless its denominator—the number of participants assessed for that endpoint—is also known. The registry record does not report the observed primary count or its denominator.

In general, a binary outcome can be described by the number of participants with the event and the number without it, alongside a clearly defined analysis population and follow-up period. A confidence interval can express the uncertainty around an estimated event frequency. It describes a range of values compatible with the data and the method used; it does not guarantee that the true value lies in that particular interval. No primary endpoint confidence interval is reported in the registry record, so there is no interval to interpret for DLTs.

Why does the design matter?

The registry identifies the study as non-randomized, open-label, and sequential. In general, randomization helps balance both measured and unmeasured participant characteristics across comparison groups. Without it, dose groups may differ for reasons other than the dose. Sequential enrollment can also mean groups are observed at different points in study conduct. The registry does not report enough detail to assess how these design features operated in this study.

Open-label means the record does not describe masking. In general, awareness of treatment can affect event reporting, assessment, or care, although the extent depends on the outcome and study procedures. The registry does not describe procedures for independent outcome assessment or blinded review. Since the primary endpoint includes judgments about treatment relationship and baseline change, such procedures could matter to interpretation, but whether they were used is not reported in the registry record.

What can the dose groups show?

Descriptive safety counts can indicate what events were recorded in a group. They do not, by themselves, estimate a causal effect of one dose versus another. A comparison would require appropriate denominators, a defined analysis population, and methods that account for the study design and uncertainty. The registry does not report a comparative analysis. The listed groups should therefore not be treated as randomized arms or as control groups.

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect. Sample-size illustrations are not observed power, and the registry does not report the sample-size justification used to plan this study.

In general, such illustrations are sensitive to the assumed effect and allocation. A planning result can help show how a future study’s required enrollment would change under different effect assumptions, but it does not describe what the current study observed. The registry record does not report numerical planning results in the registry record for this interpretation, nor does it report a randomized two-arm comparison matching those assumptions.

How should the adverse-event counts be read?

Adverse-event counts are descriptive unless accompanied by a defined comparison and analysis. A participant count affected is not necessarily the same as a count of events, because one participant may experience more than one event; the registry’s summaries do not give enough detail to resolve that distinction for every listing. Likewise, the listed serious-event terms and percentages should not be interpreted as primary DLT results. The DLT definition adds criteria for treatment relationship, severity, baseline change, and timing that the term listing does not establish.

In general, over-dispersion matters when observed variation in counts exceeds what a chosen statistical model expects. A model that assumes less variation than is present can give intervals that are too narrow or tests that are too optimistic. This is a general consideration, not a reported feature or analysis of regARDS. The record does not report a count model, an over-dispersion assessment, or a model-based estimate.

Finally, the registry reports a terminated status but does not state why the trial ended. The available record does not establish whether termination affected enrollment, follow-up, or analysis. Those details, along with missing-data procedures and analysis populations, are not reported in the registry record.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("cePolyTregs 100 x10^6 Cells Open Label", "cePolyTregs 200 x10^6 Cells Open Label")
n      <- c(3, 1)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  cePolyTregs 100 x10^6 Cells Open Label  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  cePolyTregs 200 x10^6 Cells Open Label  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of endpoints, or a procedure for adjusting for multiple comparisons. As a result, the record does not establish whether multiplicity was considered or how it would have been handled. The stated primary endpoint is a single DLT count, but the registry also lists multiple adverse-event summaries; their presence does not establish that formal hypothesis tests were conducted.

Missing-data methods are not reported in the registry record. The record does not describe how participants with incomplete follow-up, missing baseline grades, or unevaluable adverse-event information would be handled. It also does not specify an analysis population for the primary endpoint. The enrollment listing alone does not indicate how many participants contributed to the endpoint or how many had complete assessment through 28 days post infusion.

In general, these details matter because a count and its interpretation depend on who was included, what follow-up was available, and how incomplete observations were treated. When analysis populations or missing-data rules are not stated, readers cannot assess whether the reported outcome—if available—would represent all enrolled participants, treated participants, or another group. No primary outcome result is reported in the registry record, so the effects of missingness on that endpoint cannot be evaluated.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ventilator-associated pneumonia (100.0%), renal failure requiring renal replacement therapy by crrt (33.3%), aspiration (33.3%), refractory hypoxemia (33.3%).

The safety summaries report counts for two listed dose groups. For 100 x10^6 cells, the serious-event summary reports 3 at risk and 3 affected, and the other-event summary reports 3 at risk and 2 affected; deaths are listed as 2. For 200 x10^6 cells, the corresponding figures are 1 at risk and 1 affected for serious events, 1 at risk and 1 affected for other events, and 1 death. These are registry-reported counts, not a randomized comparison.

The listed serious-event terms include Ventilator-Associated Pneumonia at 100.0%; Renal Failure requiring renal replacement therapy by CRRT, Aspiration, and Refractory Hypoxemia are each listed at 33.3%. These terms and percentages are safety summaries. They do not establish that an event was caused by cePolyTregs or that it met the DLT definition. The DLT endpoint additionally requires a related TEAE of grade 3 or higher, a worsening from baseline by at least one grade, and occurrence within 28 days post infusion.

The registry listing does not include an adverse-event group for the 400 x10^6 cell dose. It also does not explain the relationship between the event-term percentages and the group-level counts. Read these figures descriptively, without inferring a dose trend or comparative risk.

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

The record describes an early-phase, non-randomized study of a single intravenous dose of cePolyTregs at listed dose levels of 100 x10^6, 200 x10^6, and 400 x10^6 cells. Its primary safety question concerns participants meeting a defined DLT threshold during 28 days after infusion. The registry reports the endpoint definition, but not the observed DLT count or a statistical analysis of that outcome.

The posted adverse-event summaries document serious events, other events, and deaths in the 100 x10^6 and 200 x10^6 groups. They provide descriptive information about events recorded in the registry, but do not establish whether those events were caused by treatment. Nor do they answer whether an event met the primary endpoint definition. The registry does not report a safety group for the 400 x10^6 dose in the adverse-event listing.

The design also limits what can be concluded from differences between listed groups. Non-randomized, sequential, open-label groups are not equivalent to randomized dose comparisons. In general, differences between groups could reflect participant characteristics, timing, or other aspects of care, as well as dose. The record does not report an analysis that separates these possibilities.

These limitations do not make the descriptive record meaningless: it identifies the intended endpoint and records safety summaries. But the registry does not report evidence that would establish efficacy, a treatment effect, a comparative dose effect, or a definitive estimate of risk. The study status is terminated, and the reason is not reported in the registry record. No conclusion about the implications of termination for follow-up or analysis can be drawn from the status alone.

14. Why This Trial Matters Statistically

This study is statistically important as an example of the distinction between a safety question and an efficacy comparison. The stated primary outcome is a participant count meeting a defined DLT threshold, not a comparative measure of clinical improvement. Early-phase studies commonly focus on characterizing safety; in general, that focus calls for careful definition of the event, follow-up window, and population being counted.

Here, the registry specifies severity, change from baseline, treatment relationship, and a 28-day period. Those criteria make clear what the endpoint is intended to capture. Yet the registry does not report the observed primary count, its denominator, or an analysis. This illustrates why a clearly specified endpoint is not enough to interpret results: readers also need the actual observations and the analysis population.

The non-randomized, sequential design is another key statistical feature. Descriptive reports can be useful for recording what happened, but groups assigned or enrolled without randomization do not provide the same basis for causal comparisons as randomized groups. The open-label nature and missing analysis details further constrain interpretation. The listed serious-event summaries can be read as safety descriptions, not as a controlled estimate of harm.

Finally, the registry’s planning assumptions should be kept separate from observed findings. Planning illustrations based on an observed effect and assumed allocation are not the study’s observed power, do not replace the trial’s own design rationale, and do not show what the study found. The registry does not report its sample-size justification. Keeping endpoint results, safety descriptions, design limitations, and hypothetical planning distinct is essential to reading this record accurately.

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 primary limitation for interpreting the main question is that the registry record does not report the observed DLT count, the primary outcome denominator, or an analysis. The follow-up window and endpoint definition are stated, but completeness of follow-up and the population assessed are not reported. This prevents estimation of the primary outcome frequency from the registry record.

The trial is listed as non-randomized, open-label, and sequential, so the dose groups are not like-for-like controls. The registry does not report the dose-sequencing rules, criteria for progression between doses, or the characteristics of participants in each group. Although the study lists three dose levels, the adverse-event group listing covers only 100 x10^6 and 200 x10^6 cells. The record does not explain the absence of a 400 x10^6 adverse-event summary.

The registry reports serious-event terms and group-level safety counts, but does not explain how the event-term percentages relate to the group counts or give enough detail to establish which events met the primary DLT criteria. The record also does not report procedures for attribution, adjudication, missing data, or analysis populations. Statistical methods beyond the endpoint definition are not reported in the registry record.

Enrollment is listed as 7 and the study status as terminated, but the reason for termination and its implications for enrollment, follow-up, or analysis are not reported. These limitations restrict interpretation to the study design and the descriptive safety information actually recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS) — NCT05027815.
• Registry record last updated 2023-06-05; status last verified 2023-05.
• Results first posted 2023-06-05.
• 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

regARDS is listed as a non-randomized, open-label, sequential Phase 1 study of cePolyTregs for ARDS associated with COVID-19. The registry title describes a Phase 1/2a study. The intervention was a single intravenous infusion, with listed dose levels of 100 x10^6, 200 x10^6, and 400 x10^6 cells. Enrollment is reported as 7; the study status is terminated.

The primary outcome counts participants with a treatment-related TEAE of NCI CTCAE 5.0 grade 3 or higher, also representing a worsening from baseline by at least one grade, within 28 days post infusion. The registry lists one outcome measure and zero analyses, and does not report the observed primary outcome result.

Adverse-event summaries are listed for the 100 x10^6 and 200 x10^6 groups. They are descriptive and do not provide a randomized comparison. The registry does not report the reason for termination, the primary analysis population, missing-data procedures, or a statistical analysis plan.