THUNDER: Acute Ischemic Stroke Study With the Penumbra System® Including Thunderbolt™ Aspiration Tubing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for THUNDER: Acute Ischemic Stroke Study With the Penumbra System® Including Thunderbolt™ Aspiration Tubing (NCT05437055), a na na study. The primary outcome is Efficacy Endpoint: Angiographic Revascularization.

2. Clinical Question

The study objective was to assess safety and efficacy in people presenting with acute ischemic stroke due to intracranial large vessel occlusion who were eligible for mechanical thrombectomy. The primary endpoint is a procedural imaging outcome: it records whether the target vessel reached the specified revascularization threshold. It is not a direct comparison of the device with another device, procedure, or usual care.

The registry also lists secondary efficacy outcomes covering revascularization after the first pass, revascularization more generally, time to revascularization, and the Modified Rankin Scale. Listed safety outcomes include symptomatic intracranial hemorrhage, all-cause mortality, and serious adverse events. The endpoint definitions and results for those secondary outcomes are not reported in the registry record. The main clinical question can therefore be described from the study objective and endpoint definition, but the registry information does not establish how often the primary outcome occurred.

3. Trial Design

THUNDER is a completed, single-group device study, registered as NCT05437055. It concerns the Penumbra System including Thunderbolt Aspiration Tubing for mechanical thrombectomy in acute ischemic stroke associated with large vessel occlusion. The record lists 216 participants as the enrollment and describes 216 evaluable participants in the ITT primary analysis population. These figures describe enrollment and the stated analysis population; they do not provide the primary endpoint result.

The record classifies the study as having a single-group model. Allocation and phase are listed as NA, and masking is listed as none. No randomized or concurrent control arm is described. Consequently, the design does not support a direct randomized comparison between the device and another treatment. Any outcome frequency in the treated group would describe that group, not the difference attributable to the device relative to a control.

The study start date is 2022-08-11, the primary completion date is 2024-09-23, and the status is completed. The registry lists the primary endpoint timeframe as up to procedure completion. It also names secondary efficacy and safety outcomes, but the detailed outcome results and analysis methods are not reported in the registry record.

The record gives the study objective as demonstrating safety and efficacy in people with acute ischemic stroke secondary to intracranial large vessel occlusion who are eligible for mechanical thrombectomy. That objective should not be mistaken for a reported conclusion. A completed status indicates the study’s registry status; it does not by itself establish that a prespecified target was met or that a treatment effect was demonstrated. The sample-size justification, protocol details, and any interim analyses are 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

Analysis population for the primary outcome, as defined in the registry: The analysis population (ITT) contains 216 evaluable participants.

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 Efficacy Endpoint: Angiographic Revascularization, measured over Up to Procedure Completion.

The primary endpoint is angiographic revascularization of the occluded target vessel after use of the Penumbra System, defined as mTICI 2b or higher. The registry describes mTICI as a scale ranging from 0-3, with higher grading representing better outcome. The endpoint timeframe is up to procedure completion, and the outcome unit is participants.

This is a binary endpoint at the participant level: each participant is classified according to whether the stated angiographic threshold was reached. In general, an imaging-based procedural endpoint can provide a standardized way to describe whether blood flow has been restored to the target vessel during the intervention. It is distinct from outcomes that assess later disability, survival, or complications. The registry separately lists the Modified Rankin Scale and several safety outcomes as secondary measures.

The record identifies 216 evaluable participants in the ITT analysis population for this endpoint, but does not report how many met the revascularization definition. The number with the event, its percentage, and any estimate of uncertainty are therefore not reported in the registry record. The endpoint definition explains what was to be counted; it does not supply the result or establish how that result compares with an alternative treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents the study as a single-group investigation of a device intervention. The primary outcome is binary at the participant level: the outcome records whether angiographic revascularization reached the defined mTICI threshold. A count outcome of this kind is commonly reported as the number of participants meeting the criterion, sometimes alongside the number assessed and an estimate of uncertainty. In this record, the outcome definition and population are stated, but the primary event count and an uncertainty estimate are not reported in the registry record.

What does a single-group design permit?

In general, a single-group study can describe outcomes among participants who receive the intervention. It cannot by itself estimate a randomized treatment contrast against a concurrent control group, because no control group is described in this record. A numerical outcome in the treated group may reflect the intervention and other influences, including participant characteristics, clinical practice, and the course of illness. Without a comparator, those influences cannot be separated through a randomized between-group contrast.

The study lists allocation as NA and masking as none. These labels do not describe random assignment or blinded assessment. The registry does not report further details about outcome adjudication, assessor procedures, or methods used to reduce bias. Those details should not be inferred from the study’s objective or its endpoint definition.

How should an estimate and its confidence interval be understood?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the method used. A narrow interval indicates greater precision, while a wide interval indicates less precision. An interval for a single-group event frequency would describe uncertainty in that frequency; it would not create a treatment comparison where none exists. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed from this information.

A p-value, in general, describes how compatible data are with a specified statistical null model, conditional on the assumptions of the test. It is not the probability that a treatment works, and a p-value alone does not express the size or clinical importance of an effect. No primary endpoint p-value or inferential analysis is reported in the registry record. The number of analyses is recorded as zero; no tests, model specifications, or multiplicity adjustments are described.

What do the sample-size assumptions mean?

The registry 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 specified as a fraction of the observed effect. These are planning assumptions, not a description of the registered single-group design. The registry record does not report that these assumptions were used to set the study enrollment, nor does it report a sample-size justification for the trial.

In general, a sample-size calculation asks how many participants would be needed under chosen assumptions to detect a specified effect with a chosen statistical procedure. Its result depends on the assumed effect, outcome variability, error rates, and design. A planning illustration is not an observed result, and it is not observed power. The figures cannot demonstrate that a study had adequate power for its actual endpoint when the underlying planning rationale and primary outcome result are not reported in the registry record.

Why is the design mismatch important?

The planning assumptions describe two equal-sized arms, whereas the registered model is single-group and no comparator is listed. A two-arm planning illustration can be useful as a hypothetical comparison scenario, but it does not turn the study into a comparative trial. It does not provide a control-arm observation or an estimate of a treatment difference. In this setting, the central statistical limitation is not resolved by a hypothetical sample-size calculation; a comparative effect requires comparative data and a suitable analysis.

The registry lists a total of eight outcome measures and identifies several secondary endpoints, but results and detailed statistical methods for those outcomes are not reported in the registry record. There is no reported information about missing-data handling, subgroup analyses, covariate adjustment, interim monitoring, or endpoint adjudication. General methods can clarify what such procedures would mean, but their use in this study cannot be assumed from the available 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("Single Arm")
n      <- c(216)
events <- c(189)
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  Single Arm  216  189  87.5  82.3  91.6  82.4  91.3  82.4  91.3

11. Multiplicity, Missing Data and Analysis Populations

The record lists eight outcome measures, including the primary angiographic revascularization endpoint and secondary efficacy and safety outcomes. It does not report analysis results for these measures; the number of analyses is recorded as zero. The statistical plan, any hierarchy among secondary outcomes, and any adjustment for multiple testing are not reported in the registry record.

In general, when many outcomes or hypotheses are tested, the chance of obtaining at least one apparently notable result by chance can increase. A prespecified testing hierarchy or multiplicity adjustment can address that issue, but neither should be presumed. Because the registry does not report inferential results or a statistical analysis plan, there is no basis to determine how multiplicity was handled or whether results were selected for reporting.

The primary analysis population is described as the ITT population and includes 216 evaluable participants. The registry does not explain how the ITT designation was applied in this single-group study, whether all enrolled participants were included in the primary analysis, or how the term “evaluable” was operationalized. Missing-data counts, reasons for missingness, and any imputation or other missing-data procedures are not reported in the registry record.

In general, missing observations can affect interpretation when the likelihood of missingness is related to the outcome or participant characteristics. The direction and scale of any resulting bias depend on the circumstances and the analysis method. Without information on missing outcomes and their handling, the robustness of the endpoint analysis cannot be assessed. Likewise, no sensitivity analysis or alternative analysis population is described in the registry record.

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: stroke in evolution (4.2%), atrial fibrillation (3.7%), acute respiratory failure (3.7%), acute kidney injury (2.3%), pneumonia aspiration (1.9%).

For the single arm, the registry reports serious adverse events for 89 of 216 participants and other adverse events for 126 of 216 participants. It also lists 24 deaths. These are participant counts, not comparisons between treatment groups. The record does not report a comparator arm, so the counts cannot be interpreted as excess risk or as evidence of a difference from another treatment.

The registry lists Stroke in evolution at 4.2%, Atrial fibrillation at 3.7%, Acute respiratory failure at 3.7%, Acute kidney injury at 2.3%, Pneumonia aspiration at 1.9%, and Brain oedema at 1.9% among the leading serious adverse-event terms. These percentages are reported as listed; the registry information does not provide further detail about event timing, duration, severity, or attribution to the device or procedure.

In general, participant counts for adverse events do not necessarily represent a count of distinct event episodes. The record does not clarify whether participants could appear in more than one event category, so the counts should not be added or treated as mutually exclusive. Nor does the list establish causality. It describes reported safety events in the study arm, while the clinical significance and comparative safety require further context not reported in the registry record.

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

The registry record establishes that THUNDER was a completed, single-group study of the Penumbra System including Thunderbolt Aspiration Tubing in people with acute ischemic stroke due to large vessel occlusion who were eligible for mechanical thrombectomy. It identifies angiographic revascularization by procedure completion as the primary endpoint and describes the threshold as mTICI 2b or higher. It also reports the stated primary analysis population and adverse-event counts.

These registry entries do not reveal the primary endpoint result. The number of participants reaching the angiographic threshold, and the precision of that result, are not reported in the registry record. The record also does not report results for the listed secondary efficacy measures, including revascularization after first pass, time to revascularization, and Modified Rankin Scale. Completion of the study and the stated objective are not substitutes for these outcome data.

The safety counts describe events in the single study arm, but they do not establish that the device caused those events. Without a control group, the counts cannot show whether an event was more or less frequent than it would have been under another treatment strategy. The record also lacks detail about event attribution and timing, so those features cannot be evaluated from the reported counts.

More broadly, this design can provide descriptive information about outcomes among participants treated in the study, but it does not provide a randomized estimate of the device’s effect relative to a comparator. No treatment-effect estimate, confidence interval, or p-value is reported for the primary outcome. Accordingly, the registry record does not establish either the size of a comparative benefit or the size of a comparative harm. Its contents support a description of the intended clinical question, registered endpoints, and reported event counts, while leaving the primary efficacy result and important analytical details unreported.

14. Why This Trial Matters Statistically

This study raises several important statistical interpretation issues common to procedural device studies. The primary outcome is a binary angiographic measure assessed by procedure completion, and the record specifies a threshold of mTICI 2b or higher. A clear operational definition is necessary for reproducible measurement, but a definition alone does not tell readers how often the endpoint occurred. Here, the primary result is not reported in the registry record, so the endpoint’s observed frequency and precision cannot be evaluated.

The single-group structure also shapes what can be learned. A treated-group event frequency is descriptive; it does not estimate how outcomes would differ under an alternative strategy. This distinction is especially important when a study objective refers to efficacy or safety, terms that may sound comparative even when the design has no comparator. Statistical interpretation must follow the actual design rather than the language of the objective.

The registry’s planning assumptions describe a hypothetical two-arm calculation, while the recorded study model is single-group. Keeping planning illustrations separate from trial results prevents a common error: treating a sample-size scenario as evidence that a treatment effect was observed or adequately tested. A planning calculation is conditional on assumptions and is not observed power.

Finally, the listed secondary outcomes and adverse-event counts show why transparent reporting matters. Readers need outcome results, analysis populations, missing-data information, and methods for handling multiple outcomes to judge how complete and precise the evidence is. Those details are not reported in the registry record. The trial is statistically informative as an example of why endpoint definitions, study design, reported results, and inferential claims must be distinguished.

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 central limitation of the available registry information is that the primary endpoint result is not reported in the registry record. Although the endpoint definition, timeframe, and analysis population are stated, there is no event count or uncertainty estimate with which to assess the observed angiographic outcome. Results for the listed secondary outcomes are also not reported in the registry record.

The single-group model and absence of a comparator limit interpretation to descriptive outcomes among treated participants. The record does not support a randomized estimate of a treatment difference, and the adverse-event counts cannot be compared with a control group. Event attribution and timing are not reported, which further limits interpretation of the safety information.

Other important details are not reported in the registry record, including the statistical analysis plan, sample-size justification, missing-data methods, outcome adjudication procedures, and whether any interim analyses occurred. The record identifies 216 evaluable participants in the ITT population, but does not explain how evaluability was determined or describe the handling of participants without endpoint data. It also does not specify how multiple outcomes were managed statistically.

The planning assumptions refer to a hypothetical two-arm calculation and should not be taken as the design or result of this single-group study. Together, these limitations mean that the registry supports a description of the study structure and recorded safety counts, but leaves the primary efficacy result and several features needed for a fuller statistical assessment unavailable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: THUNDER: Acute Ischemic Stroke Study With the Penumbra System® Including Thunderbolt™ Aspiration Tubing — NCT05437055.
• Registry record last updated 2026-11-03; status last verified 2026-10.
• Results first posted 2026-11-03.
• 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

NCT05437055, THUNDER, is a completed single-group study of the Penumbra System including Thunderbolt Aspiration Tubing for mechanical thrombectomy in acute ischemic stroke associated with large vessel occlusion. The registry lists enrollment of 216, a study start date of 2022-08-11, and a primary completion date of 2024-09-23. Masking is listed as none, and allocation and phase are listed as NA.

The primary outcome is angiographic revascularization of the occluded target vessel, defined as mTICI 2b or higher up to procedure completion. The ITT primary analysis population is described as 216 evaluable participants, but the primary endpoint result is not reported in the registry record. Safety counts for the single arm include serious adverse events in 89 of 216 participants, other adverse events in 126 of 216, and 24 deaths. The record does not provide a comparator or detailed inferential analyses.