A Study of Patients With Lower Extremity Acute Limb Ischemia to Remove Thrombus With the Indigo Aspiration System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Patients With Lower Extremity Acute Limb Ischemia to Remove Thrombus With the Indigo Aspiration System (NCT04144959), a registered phase not stated study. The primary outcome is Target Limb Salvage Rate.

2. Clinical Question

The question is about a defined outcome after use of the device in the stated clinical population. It is not a comparison of outcomes between randomized treatment groups. Without a control comparison, the record cannot establish how the measured outcome would differ under another treatment or under usual care.

The registry also lists secondary outcomes covering technical success, runoff score, Rutherford classification, vessel patency, limb salvage, device-related serious adverse events, major bleeding, and mortality. Their inclusion identifies outcomes of interest, but does not by itself provide results for those outcomes. The primary endpoint result and the results for these secondary measures are not reported in the registry record.

3. Trial Design

STRIDE is a completed study sponsored by Penumbra Inc. Its registry title describes a study of patients with lower extremity acute limb ischemia using the Indigo Aspiration System to remove thrombus. The brief objective is to collect safety and performance data for the device in this population. Enrollment is reported as 119.

The listed intervention is a device, the Indigo Aspiration System. The registry describes patients with lower extremity acute limb ischemia, but does not give further details about eligibility criteria or the treatment protocol. The arm description contains no additional information. Allocation is not stated, and the registry identifies the study as not being a randomized comparison. A like-for-like control group is therefore not described in the record.

The study start date is 2019-12-17, and the primary completion date is 2023-01-02. Its status is COMPLETED. These dates and status describe the study record; they do not establish when all analyses were performed or when results were finalized.

The primary outcome is Target Limb Salvage Rate, assessed at 1-Month Post Procedure. Its analysis population is described as ITT and contains 111 evaluable participants. The record does not give the definition of evaluability, explain how the analysis population was assembled, or describe the handling of participants without an evaluable outcome.

Further design details, including the statistical plan, sample-size justification, and any interim analyses, are not reported in the registry record. The planning assumptions stated with the sample-size illustrations should not be mistaken for a description of the study’s actual allocation or design.

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 111 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 Target Limb Salvage Rate, measured over 1-Month Post Procedure.

The primary endpoint is Target Limb Salvage Rate, measured as the proportion of participants who did not have a major amputation above the level of the tarsometatarsal joint at 1-Month Post Procedure. The outcome is binary at the participant level: a participant either meets the stated limb-salvage definition or does not. The measure is expressed as a proportion rather than as a count of procedures or as time until an event.

As a general statistical rationale, a limb-salvage measure captures whether a specified serious outcome occurred during a stated follow-up period. A clearly defined threshold for major amputation makes the endpoint interpretable, while the follow-up time gives the result a specific temporal context. The endpoint reflects only the definition in the registry; it does not capture every dimension of recovery, function, or safety.

The listed analysis population is ITT and contains 111 evaluable participants. The registry does not report the number meeting the limb-salvage definition, the observed proportion, a confidence interval, or a test result. Consequently, the primary endpoint’s magnitude and statistical precision cannot be assessed from the result information in this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant outcome. In general, a binary outcome records whether a defined event or condition is present for each participant. The registry’s definition classifies participants according to whether they did not have a major amputation above the specified anatomical level during the stated follow-up period. A proportion is ordinarily formed by relating the number meeting the definition to the number assessed. The record gives the analysis population description, but does not report the number meeting the endpoint or the resulting proportion.

What does an estimate describe?

An estimate is a numerical summary of the observed data. For a binary endpoint, an estimated proportion describes the share of participants in the analysis population who meet the endpoint definition. It is tied to that population, outcome definition, and follow-up period. It is not automatically an estimate for every patient with the condition, nor does it explain why outcomes occurred. Because the observed endpoint count and proportion are not reported in the registry record, the magnitude of the primary result cannot be interpreted.

Why does uncertainty matter?

General statistical interpretation considers both the estimate and its uncertainty. A confidence interval communicates how much sampling uncertainty is associated with an estimate under the method’s assumptions. A narrow interval generally indicates greater precision than a wide interval, while neither interval width nor the estimate alone addresses possible bias, incomplete follow-up, or limits on generalizability. No confidence interval for the primary endpoint is reported in the registry record. No formal primary-endpoint test result is reported either.

What can a significance test establish?

In general, a significance test evaluates compatibility between observed data and a specified statistical model or null hypothesis. A small p-value is not a measure of clinical importance, does not prove causation, and does not show the probability that the null hypothesis is true. A large p-value does not prove that there is no difference or effect. Interpretation depends on the question, design, assumptions, and reported estimate. The record does not provide a primary endpoint p-value or a hypothesis-testing plan, so no inferential conclusion should be attributed to it.

How should planning calculations be read?

The stated sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They define the effect to detect as a stated fraction of the observed effect. These are planning assumptions for illustrations, not a description of the trial’s actual design. In particular, equal allocation between arms in a planning calculation does not imply that STRIDE had randomized arms; the registry says this is not a randomized comparison and that allocation is not stated.

Such calculations are hypothetical: they describe the sample size or event total that a design might require under chosen assumptions. They are not observed power. Power is a design property under a specified set of assumptions, not a retrospective way to decide whether a result is convincing. The registry’s actual sample-size justification is not reported. No numerical planning results are stated in the record, so none can be interpreted as an observed trial finding.

The assumptions also distinguish participant-based calculations from time-to-event calculations. The stated method uses a total number of events for time-to-event illustrations based on Schoenfeld, whereas other illustrations use participants per arm. These planning conventions do not indicate that the primary endpoint was analyzed as a time-to-event outcome: the registry defines it as a proportion of participants at 1-Month Post Procedure.

What does the design allow readers to compare?

As a general principle, a randomized comparison can support a treatment contrast by comparing outcomes across assigned groups, subject to the design and analysis assumptions. The registry does not describe such a comparison for STRIDE. It identifies a patient group and the device intervention, and notes that allocation is not stated. An outcome proportion in this setting, if reported, would describe outcomes among the analyzed participants; it would not by itself estimate a causal difference from a control treatment.

For this record, the reported details support describing the endpoint definition, analysis population, study objective, and safety counts. They do not support reconstructing an unreported endpoint estimate, confidence interval, statistical test, or adjusted analysis. The statistical analysis plan, specific models, and any interim analyses 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("Patients With Lower Extremity Acute Limb Ischemia")
n      <- c(111)
events <- c(109)
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  Patients With Lower Extremity Acute Limb Ischemia  111  109  98.2  93.6  99.8  93.7  99.5  93.7  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary Target Limb Salvage Rate endpoint. When a study evaluates multiple outcomes or performs multiple tests, the chance of obtaining at least one apparently notable result can increase. General approaches to multiplicity include prioritizing a primary endpoint, adjusting inference across a family of tests, or labeling secondary analyses as exploratory. Which approach was planned for STRIDE is not reported in the registry record.

The record names technical success, Modified Society for Vascular Surgery Runoff Score, Improvement of Rutherford Classification, Vessel Patency, Target Limb Salvage Rate, device-related serious adverse events, major bleeding peri-procedure, and mortality among its secondary outcomes. It does not provide the results or analysis details for these measures in the registry record. The number of outcome measures is reported as 9, while the number of analyses is reported as 0. The record does not explain this distinction or provide an analysis plan to clarify it.

For the primary endpoint, the analysis population is described as ITT and contains 111 evaluable participants. The overall enrollment is 119. The record does not explain the difference between the enrollment and evaluable analysis population, state how participants without an evaluable endpoint were handled, or describe imputation, exclusions, or sensitivity analyses. It is therefore not possible to assess the potential impact of missing outcome information from this record.

General interpretation of missing data depends on why data are missing and how missingness relates to outcomes and participant characteristics. The registry does not report those details, so it would be inappropriate to assume that missing outcomes had no effect or to assign them an outcome category. Details about outcome ascertainment, the analysis population beyond its brief description, multiplicity control, and sensitivity analyses are not reported 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: haemorrhage (13.4%), peripheral ischaemia (13.4%), peripheral artery occlusion (5.0%), peripheral artery thrombosis (5.0%), atrial fibrillation (4.2%).

The safety summary lists 119 participants at risk for serious adverse events and reports 90 participants with a serious adverse event. It also lists 119 at risk for other adverse events and reports 15 participants with an event in that category. Deaths are reported as 12. These are registry-record counts, not estimates of a treatment effect against a control group. The record does not state whether the death count overlaps with the adverse-event counts.

The listed serious adverse event terms include Haemorrhage at 13.4%, Peripheral ischaemia at 13.4%, Peripheral artery occlusion at 5.0%, Peripheral artery thrombosis at 5.0%, Atrial fibrillation at 4.2%, and Sepsis at 3.4%. These are registry-reported frequencies for the named terms. The record does not specify the denominator or explain whether participants could contribute to more than one term, so the percentages should not be added or treated as mutually exclusive categories.

Counts and listed event terms describe what was recorded; they do not establish that the device caused the events. Although device-related serious adverse events are listed among the secondary outcomes, the record does not give a device-causality breakdown. The timing, severity grading, event adjudication procedures, and relationship assessments are not reported in the registry record.

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

The record establishes that STRIDE was a completed study of the Indigo Aspiration System in patients with lower extremity acute limb ischemia, with a stated objective of collecting safety and performance data. It specifies a primary outcome focused on the proportion of participants without a major amputation above the level of the tarsometatarsal joint at 1-Month Post Procedure. It also provides the stated analysis population and some safety counts.

It does not establish the observed target limb salvage rate. The primary endpoint count, proportion, confidence interval, and test result are not reported in the registry record. Without those results, readers cannot judge the observed frequency of the endpoint or the precision of an estimate. The absence of a reported result should not be interpreted as a favorable or unfavorable outcome.

Even if an outcome estimate were available, the record does not describe a randomized control comparison. Thus, a rate among the treated participants would not alone show what would have happened with another treatment, nor would it isolate the device’s causal contribution. The registry does not report enough design or analysis detail to resolve potential differences in patient characteristics, care, follow-up, or outcome ascertainment.

The safety counts indicate that adverse events and deaths were recorded, but do not establish causation. They also do not provide a complete safety interpretation without details about event timing, relatedness, definitions, and possible overlap among categories. Device-related serious adverse events are listed as an outcome, but a result for that measure is not reported in the registry record.

Accordingly, the record is informative about the clinical question, endpoint definition, study status, and reported safety counts, but the primary result is not available for statistical evaluation. It does not support a claim that the device does or does not work, or a comparison with an alternative. Those conclusions would require outcome results and a design and analysis capable of addressing the relevant comparison.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why a named endpoint and an endpoint result are different kinds of information. STRIDE defines Target Limb Salvage Rate, identifies its follow-up time, and describes an analysis population. Yet the registry record does not report the number of participants meeting the endpoint or its estimated proportion. Without that estimate, the primary outcome cannot be evaluated for magnitude or precision.

The design context is also essential. The record does not describe a randomized comparison, and allocation is not stated. This means that a group’s outcome frequency, if available, would answer a descriptive question about the participants observed; it would not by itself answer a causal question about how outcomes compare under different treatments. Statistical methods cannot create a valid control comparison where the design does not provide one.

The safety summary further illustrates the difference between event counts and causal attribution. It reports serious adverse events, other adverse events, deaths, and selected serious-event terms. Those figures can describe recorded safety experience, but they do not establish whether the device caused the events. For that interpretation, relatedness assessments and additional design and follow-up details would be needed; these are not reported in the registry record.

Finally, planning assumptions should remain separate from observed evidence. A sample-size illustration based on an observed effect and specified assumptions is a hypothetical design aid, not observed power and not a substitute for the endpoint estimate. Separating design assumptions, observed outcomes, uncertainty, and causal claims helps readers identify exactly what the record can support and where its limits remain.

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 endpoint’s observed value is not reported in the registry record. The record gives its definition and states that the ITT analysis population contains 111 evaluable participants, but does not provide the number meeting the endpoint, the estimated proportion, or an uncertainty interval. This prevents assessment of the primary result’s size and precision.

The record does not describe a randomized comparison, and allocation is not stated. It does not identify a control treatment or provide a like-for-like comparator. Consequently, the available information cannot isolate a treatment effect from the outcomes observed in the patient group. Details of eligibility criteria, intervention delivery, co-interventions, and follow-up procedures are not reported in the registry record.

The record reports enrollment of 119 and an evaluable analysis population of 111, but does not explain how participants became nonevaluable or how missing outcome data were handled. It does not report imputation, sensitivity analyses, or other checks on the influence of missing data. The analysis population description alone is insufficient to assess those issues.

Safety interpretation is limited by the lack of reported detail on event timing, event adjudication, device relatedness, and category overlap. The listed term percentages do not have a stated denominator in the information summarized, and the record does not explain whether the same participant could appear under multiple terms. Counts of participants with events should not be interpreted as counts of all event episodes.

The statistical plan, sample-size justification, multiplicity approach, specific analysis methods, and interim analyses are not reported in the registry record. These omissions constrain assessment of whether the reported outcomes were analyzed as planned and how uncertainty or multiple outcomes were handled.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Patients With Lower Extremity Acute Limb Ischemia to Remove Thrombus With the Indigo Aspiration System — NCT04144959.
• Registry record last updated 2025-06-27; status last verified 2025-06.
• Results first posted 2025-06-27.
• 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

STRIDE (NCT04144959) is a completed study sponsored by Penumbra Inc. of the Indigo Aspiration System in patients with lower extremity acute limb ischemia. Enrollment is reported as 119. The primary objective was to collect safety and performance data.

The primary endpoint is Target Limb Salvage Rate at 1-Month Post Procedure, defined as the proportion without a major amputation above the level of the tarsometatarsal joint. The record describes an ITT analysis population of 111 evaluable participants but does not report the endpoint result.

Safety counts include 90 participants with serious adverse events, 15 with other adverse events, and 12 deaths. The registry does not report a randomized comparison, and allocation is not stated. Statistical analysis, missing-data handling, and multiplicity details are not reported in the registry record.