Extracorporeal Membrane Oxygenation (ECMO) in Non-intubated Patients With Acute Respiratory Distress Syndrome (ARDS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extracorporeal Membrane Oxygenation (ECMO) in Non-intubated Patients With Acute Respiratory Distress Syndrome (ARDS) (NCT01669863), a na phase 1, phase 2 study. The primary outcome is Number of Participants That Did Not Require Endotrachael Intubation.

2. Clinical Question

In statistical terms, this is a feasibility question in a small, uncontrolled pilot. It asks whether avoidance of intubation was observed often enough to meet the study’s stated threshold, not whether ECMO caused that outcome. Without a comparator, the record cannot separate an effect of the intervention from the course of illness, patient selection, or other care. The registry’s description says that a subsequent larger study would be intended to better define the patient population most likely to respond. That proposed next step is distinct from evidence of efficacy in this pilot. The missing primary endpoint result also means that the stated decision rule cannot be evaluated from the posted registry information.

3. Trial Design

NCT01669863 is a completed, investigator-initiated, single-center proof-of-concept study sponsored by Hannover Medical School. Its official title describes awake ECMO for acute respiratory failure as a non-controlled study. The registry classifies it as a single-group study with allocation not applicable and no masking. The listed phases are Phase 1 and Phase 2. Enrollment is listed as 6. The registry gives a start date of 2012-08 and primary completion date of 2013-04.

The study focused on ECMO use in non-intubated patients with ARDS. The intervention listings name ECMO as a device and ECMO in non-intubated patients as a procedure. The arm description says ECMO would be used in non-intubated patients with ARDS. The brief summary characterizes the purpose as addressing the feasibility of awake ECMO in acute respiratory failure. These descriptions establish the clinical focus, but do not provide a detailed protocol or eligibility criteria.

Because all participants were in one group, there was no concurrent control arm and no randomized allocation. The record therefore supports a descriptive account of outcomes in the study group, not a treatment contrast. The absence of masking is also recorded, but the registry does not explain how outcome assessment was conducted. The record lists three outcome measures and zero analyses. It does not give a statistical analysis plan, information about interim analyses, or details about how the analysis population was defined.

The primary outcome was a count of participants who did not require endotracheal intubation during the duration of ICU stay. The registry describes a prespecified feasibility threshold: avoidance in 2 or more of the 6 participants would be considered positive and would lead to a larger trial. This is a pilot decision rule, not a comparative efficacy test. The record is marked completed, but completion status does not establish that the primary result was posted. The primary endpoint count is not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

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 That Did Not Require Endotrachael Intubation, measured over Duration of ICU stay.

The primary endpoint counts participants who did not require endotracheal intubation during the duration of ICU stay. It is a binary outcome at the participant level: each participant either met the stated outcome or did not. The registry labels the measure as a number of participants, rather than a rate over time or a measure of oxygenation. The endpoint therefore captures whether intubation was avoided during the specified period, not how long it was avoided or the degree of respiratory support required.

The registry’s stated reason for using this measure is its role in an exploratory feasibility decision. If 2 or more of the 6 planned participants avoided intubation, the trial would be considered positive and a larger study would be the next step. This threshold provides a simple go-forward criterion for a pilot; it is not a comparison against an untreated group and does not by itself establish that ECMO caused the outcome.

The endpoint’s usefulness depends on a clear definition of the observation period and the event. The registry names the duration of ICU stay, but does not report further operational details about assessment, follow-up, or handling of participants with incomplete outcome information. Most importantly, the observed count for this endpoint is not reported in the registry record. Accordingly, it is not possible to determine whether the stated feasibility criterion was met from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical feature is the single-group design. Participants were observed in one intervention group, with no control arm and no random allocation. Such a design can describe outcomes within the group, but cannot estimate a between-group treatment difference. A change or outcome observed after an intervention may have multiple explanations, including the clinical course and other care. General statistical principle: a concurrent comparison group helps separate treatment contrasts from background changes and differences in patient prognosis. That kind of contrast is unavailable in this study.

What does the primary endpoint count?

The endpoint is a participant count: the number who did not require endotracheal intubation during the duration of ICU stay. This is a binary outcome for each participant. A count is intuitive in a small pilot, and the registry gives a threshold for deciding whether to proceed to a larger study. The stated rule was that the trial would be considered positive if intubation could be avoided in 2 or more of the 6 participants. That rule is a decision criterion, not an estimate of a treatment effect. The observed count is not reported in the registry record, so neither the endpoint result nor whether the criterion was reached can be established from the posted information.

What can an estimate and its uncertainty tell readers?

General statistical explanation: an estimate describes the value suggested by the observed data, while a confidence interval describes the range of values compatible with the data under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on the design and the quantity being estimated. For a binary outcome in a small group, the estimate can be sensitive to each participant’s outcome. Confidence intervals can help communicate that uncertainty rather than presenting a count as if it were exact evidence about a wider population.

No confidence interval or primary endpoint estimate is reported in the registry record. The registry lists zero analyses, and no analysis methods for the primary outcome are reported. It would therefore be inappropriate to attribute an interval method, hypothesis test, adjusted model, or inferential conclusion to the study. General methods such as exact binomial intervals can be used for binary outcomes, but the record does not say that one was used.

How should the planning illustrations be understood?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; other illustrations are expressed as participants per arm. These are planning assumptions, not a description of this trial’s single-group design. In particular, the two-arm allocation assumption does not change the actual registry classification, which is single group.

General statistical explanation: a planning calculation asks how much information a future study might need under specified assumptions. The result depends on the chosen effect, variability, outcome type, allocation, and analysis method. If an assumed effect is smaller, detecting it generally requires more information, all else being equal. Planning values are not observed power and do not show that the completed study had a particular probability of detecting an effect. The record does not report the calculation outputs in the registry record for interpretation, and the observed primary endpoint result needed to anchor the stated effect is also not reported.

Why does over-dispersion matter in some outcomes?

General statistical explanation: count outcomes may vary more than a simple model assumes. Over-dispersion means that the observed variability exceeds the model’s expected variability. If ignored, standard errors may be too small, confidence intervals too narrow, and tests too optimistic. A suitable analysis may account for extra variability, but the choice depends on how the outcome is generated and on the design. This endpoint is described as a participant count for a binary outcome, and the registry does not report a count model, an over-dispersion assessment, or any analysis. Over-dispersion should not be presumed to have been tested or corrected.

What does the absence of analyses imply?

The registry lists three outcome measures and zero analyses. That does not establish that no analysis was conducted outside the registry; it means analysis results and methods are not reported in the registry record. There is no reported primary endpoint count, interval estimate, p-value, or adjusted result to interpret. Statistical explanations can clarify how such quantities would normally be used, but they cannot substitute for missing results. The strongest reading is therefore design-based: the trial set out to assess feasibility using a stated threshold, but the posted record does not disclose whether the threshold was met.

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("Use of ECMO in Non-intubated Patients")
n      <- c(6)
events <- c(3)
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  Use of ECMO in Non-intubated Patients  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but the information available does not identify a hierarchy among all outcomes, describe an adjustment for multiple testing, or state how multiplicity was handled. It lists zero analyses. The presence of several outcomes can raise multiplicity concerns when multiple statistical tests are performed, because repeated testing can increase the chance of a false-positive finding. General statistical explanation: a prespecified primary outcome and analysis plan can clarify which result is confirmatory and how secondary outcomes should be interpreted. The registry record does not report such a plan, so no multiplicity adjustment or testing strategy should be assumed.

The primary endpoint is described as a count and has a stated feasibility threshold, but its observed result is not reported in the registry record. No confidence interval or test result is reported for it. The record also does not report the analysis population, whether all enrolled participants were included in the primary outcome assessment, or whether any participants were excluded from analysis.

Missing-data methods and the amount of missing outcome information are not reported in the registry record. It is therefore not possible to determine whether any participants had incomplete endpoint data, how missingness was handled, or whether sensitivity analyses were performed. General statistical principle: missing data can affect an estimate if the likelihood of missingness is related to outcome or participant characteristics. The appropriate assessment depends on the amount and reasons for missingness, none of which are described in the registry record.

The registry lists enrollment as 6, but it does not provide a participant flow account or a clear analysis denominator for the primary endpoint. No analysis populations, such as an intention-to-treat or per-protocol population, are reported. These gaps limit assessment of how completely the posted results, if any, represent the enrolled group.

12. Safety Results

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

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: accidental ecmo line removal (16.7%).

The registry reports serious adverse event information for the group titled Use of ECMO in Non-intubated Patients. It lists 6 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 6 at risk and 0 affected. These are counts in the registry record; they do not provide a comparative safety estimate because the study had no control group.

Accidental ECMO line removal is listed among the serious adverse event terms at 16.7%. That term should be read as a reported safety item, not as a complete account of all possible complications or as a comparative rate. The registry’s secondary outcome specifically concerns the number of participants who presented with ECMO-related complications, but the listed information does not provide a fuller event-level narrative or additional analysis.

Deaths are not reported in the registry record; a missing death value should not be interpreted as zero deaths. The record does not report the timing, duration, severity grading, resolution, or investigator assessment of relationship to ECMO for the serious event. General statistical principle: adverse event counts in a small, uncontrolled study are descriptive. They can identify events recorded during the study, but cannot alone establish the frequency of risk in a broader population or attribute an event causally to the intervention.

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

The record establishes that this was a completed, single-group proof-of-concept study of awake ECMO in non-intubated patients with ARDS. Its main feasibility question concerned avoiding endotracheal intubation during the duration of ICU stay. The registry specified that avoidance in 2 or more of the 6 participants would make the pilot positive and lead to a larger trial. The actual primary endpoint count is not reported in the registry record, so the central result cannot be determined from the posted information.

This distinction between a design rule and a result is essential. The stated threshold expresses what investigators planned to regard as a promising feasibility signal. It does not show that the outcome occurred, and it is not evidence that ECMO caused an outcome. A pilot threshold is also not a substitute for a randomized comparison or a precise estimate of treatment effect.

The single-group design can describe what was recorded in the intervention group, but there is no comparator from which to estimate what would have happened under another approach. The registry does not report a statistical analysis plan, primary endpoint estimate, confidence interval, or analysis population. These omissions prevent assessment of the primary result’s magnitude and precision. The record also leaves eligibility details, missing-data handling, and endpoint assessment procedures unreported.

The safety record lists 1 serious adverse event participant among 6 at risk, 0 participants with other adverse events among 6 at risk, and accidental ECMO line removal at 16.7% among the serious adverse event terms. Those data describe reported events; without fuller context or a comparison group, they do not establish a comparative safety profile. Deaths are not reported in the registry record.

The study’s statistical meaning is therefore limited but specific: it documents a feasibility objective and a planned decision threshold, alongside sparse safety counts. It does not permit a conclusion about whether the primary threshold was met, how precisely the endpoint was estimated, or whether ECMO improved outcomes relative to another strategy. The proposed larger study described in the registry would be needed to address a broader patient-selection question, but the record does not establish its design or results.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a feasibility signal and an estimate of comparative effectiveness. The registry frames the study as a proof-of-concept investigation and defines a threshold for considering a larger study. Such a rule can help organize a pilot around a practical next-step decision. It is not equivalent to a randomized treatment comparison, nor does it establish that an observed outcome was caused by the intervention.

The design also makes the limits of descriptive counts visible. The primary endpoint is a count of participants who avoided intubation over the duration of ICU stay. A count can be easy to interpret, but its meaning depends on the denominator, outcome definition, and completeness of follow-up. The registry lists enrollment as 6, yet does not report the observed primary endpoint count or an analysis denominator. Readers therefore cannot assess even the stated pilot threshold from the posted record.

The case also shows why uncertainty belongs beside a result. General statistical principle: small studies tend to provide limited precision, and an observed count may be compatible with a range of underlying outcome probabilities. An estimate and interval can make that uncertainty explicit. No primary estimate or confidence interval is reported in the registry record, so the intended feasibility result cannot be judged for precision.

Finally, the trial demonstrates the importance of distinguishing design assumptions from observed evidence. Planning illustrations that assume equal allocation between two arms do not describe this single-group study. Planning calculations are useful for designing future studies when their assumptions are transparent, but they cannot recover an unreported outcome or serve as observed power. The registry’s limited record supports careful description, while also showing why outcome reporting and analysis details are essential for interpretation.

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.

Several trial-specific limitations constrain interpretation. The study was non-controlled and single group, with allocation listed as not applicable. Consequently, there is no like-for-like control comparison and no basis in this record for estimating a treatment contrast. The registry also lists no masking. It does not describe how the primary outcome was assessed, whether assessment was standardized, or how decisions about intubation were made.

The primary endpoint is framed as avoiding endotracheal intubation during the duration of ICU stay, but the observed count is not reported in the registry record. The registry’s stated threshold can therefore not be evaluated. Enrollment is listed as 6, but the record does not give participant flow, the number assessed for the endpoint, or an analysis denominator. Missing-data handling and analysis populations are not reported.

Eligibility criteria and participant characteristics beyond the stated focus on non-intubated patients with ARDS are not reported in the registry record. This limits assessment of who the findings might represent and how broadly the feasibility question applies. The record names a single center, but does not provide further information about implementation or care context.

The registry lists three outcome measures and zero analyses. It does not report a statistical analysis plan, confidence interval, inferential result, multiplicity approach, or details of outcome assessment. Safety reporting is also limited: serious event counts are listed, but event timing, severity grading, relationship assessment, and deaths are not reported in the registry record. These gaps mean that the posted information permits only a narrow description of the study’s intent and reported safety counts, not a comprehensive evaluation of outcome magnitude, precision, or causality.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Extracorporeal Membrane Oxygenation (ECMO) in Non-intubated Patients With Acute Respiratory Distress Syndrome (ARDS) — NCT01669863.
• Registry record last updated 2015-04-23; status last verified 2015-03.
• Results first posted 2015-04-23.
• 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

NCT01669863 is a completed, single-center, investigator-initiated Phase 1 and Phase 2 proof-of-concept study sponsored by Hannover Medical School. It examined awake ECMO in non-intubated patients with ARDS and acute respiratory failure. The registry lists enrollment as 6, identifies a single-group model, and reports no masking or randomized allocation.

The primary endpoint counted participants who did not require endotracheal intubation during the duration of ICU stay. The planned criterion was avoidance in 2 or more of the 6 participants. The observed primary result is not reported in the registry record, which also lists zero analyses and does not report an analysis plan or analysis population.

The safety record lists 1 participant with a serious adverse event among 6 at risk and 0 with other adverse events among 6 at risk. Accidental ECMO line removal is listed at 16.7% among serious adverse event terms. Deaths are not reported in the registry record. The single-group design and missing primary result limit conclusions to the study’s stated feasibility objective and the safety counts recorded.