GORE Embolic Protection With Reverse Flow: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for GORE Embolic Protection With Reverse Flow (NCT00594100), a na phase 3 study. The primary outcome is Composite Major Adverse Event (MAE) Rate.

2. Clinical Question

This is a single-group evaluation, not a randomized comparison of the Flow Reversal System against a concurrent control group. The registry record identifies the study as a Phase 3 device study and describes its purpose as comparing 30-day safety and efficacy with a benchmark derived from other distal embolic protection studies. Consequently, the question is about the observed outcomes in the study group and their relation to that external criterion, not about a randomized estimate of treatment differences.

The primary outcome combines death, stroke, myocardial infarction, and transient ischemic attack through the 30-day follow-up. The registry record says the endpoint is non-hierarchical and adjudicated by an independent Clinical Events Committee. The numerical primary endpoint result, the benchmark value, and a statistical comparison with that benchmark are not reported in the registry record. Therefore, the clinical question can be identified from the record, but its answer cannot be established in the registry record recorded.

3. Trial Design

The study is titled GORE Embolic Protection With Reverse Flow, with an official title describing the GORE Neuro Protection System in carotid stenting of subjects at high risk for carotid endarterectomy. It is recorded as Phase 3, completed, and single-group. Allocation is listed as not applicable, and masking is listed as none. The record gives enrollment as 245. The study started in 2006-07, and primary completion was in 2008-09.

The intervention was the GORE Flow Reversal System, a device used for embolic protection during carotid artery stenting. The pivotal group is described as all non-training subjects using the system during stenting, excluding the first two subjects accounted for in Training Cases. The record does not report how many participants were in the pivotal group or how many were evaluable for the primary endpoint. Enrollment should therefore not be treated as the primary endpoint denominator.

The study summary describes a comparison of 30-day safety and efficacy with an Objective Performance Criterion derived from distal embolic protection studies. It does not describe a concurrently randomized control arm. The numerical criterion, the method used to derive it, and the precise statistical procedure for comparing study outcomes with it are not reported in the registry record.

The listed secondary outcomes are Flow Reversal System Technical Success, Flow Reversal System Success, Stent Success, Clinical Success, and Patency at 30 Days. Their numerical results and operational definitions are not reported in the registry record. The record identifies six outcome measures overall, but the presence of an outcome name alone does not establish its result or analysis method.

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.

Procedure

Reasons for not completing this period:

Follow-up Through 30 Days Post Procedure

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All primary endpoint evaluable subjects

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 Composite Major Adverse Event (MAE) Rate, measured over Treatment through 30-day visit window.

The primary endpoint is the number of participants with one or more major adverse events from treatment through the 30-day visit window. The composite includes death, stroke, myocardial infarction, and transient ischemic attack. It is described as non-hierarchical, so the record does not specify a priority ordering among those event types. An independent Clinical Events Committee adjudicated the major adverse events.

A composite endpoint can represent several clinically important event types in one outcome. In general, this can make an endpoint more inclusive than any single component and can support an overall assessment of a defined set of harms or complications. Its interpretation depends on the components, the follow-up window, and how events are counted. An overall composite does not by itself reveal how many participants experienced each component or whether the components contributed similarly.

The registry record identifies all primary endpoint evaluable subjects as the endpoint population, but does not give the number of evaluable subjects, the event count, or the resulting rate. The record also does not give component-specific counts. The endpoint definition is therefore clear, while its observed magnitude and precision are not reported in the registry record. The serious and other adverse-event figures should not be substituted for this primary outcome: the record does not establish that those categories are identical to the adjudicated composite endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: a participant either had one or more qualifying major adverse events during the specified follow-up window or did not. The outcome is expressed as a number of participants with an event. For a binary endpoint, an event count is usually interpreted alongside the number of participants assessed, because the count alone does not establish the event rate. Here, the record names the primary endpoint population as all primary endpoint evaluable subjects, but its size and the event count are not reported in the registry record.

What does a single-group benchmark comparison estimate?

The study has one treatment group and an external Objective Performance Criterion. In general, a benchmark comparison asks whether the observed outcome in a study group is compatible with a prespecified or otherwise selected reference value. It does not create the same direct protection against bias as random assignment to a concurrent control group. Differences between the study and the studies used to derive a benchmark can affect interpretation, including differences in participant characteristics, outcome definitions, follow-up, clinical practice, and event ascertainment. These are general considerations; the numerical benchmark, its derivation, and the statistical test used in this study are not reported in the registry record.

Without the primary endpoint result and the benchmark value, the direction and size of any comparison cannot be evaluated. The record does not report a confidence interval, test statistic, or p-value for the primary endpoint comparison. It is therefore not possible to tell from the recorded details how compatible the observed result was with the benchmark or how precisely that relationship was estimated.

What does an interval estimate add?

In general, a confidence interval communicates uncertainty around an estimate. For an event rate, it conveys how much sampling uncertainty remains around the estimated frequency. For a comparison with a benchmark, an interval for the difference can show which values remain compatible with the data under the method used. An interval is not a guarantee that the true value lies within its limits, and it does not resolve concerns about study design or benchmark comparability. No interval for the primary endpoint is reported in the registry record.

How should the composite endpoint be understood?

The composite combines death, stroke, myocardial infarction, and transient ischemic attack. In general, combining outcomes can increase the number of events available for an overall analysis, but the combined estimate can conceal differences among components. A participant meeting more than one component is counted only once for the stated endpoint of one or more events, although the record does not specify the detailed counting rules beyond its non-hierarchical description. Component counts and the primary endpoint count are not reported in the registry record.

Independent adjudication by a Clinical Events Committee is part of the endpoint definition. In general, independent adjudication can provide a consistent review of whether reported events meet endpoint criteria. It does not, by itself, establish how complete follow-up was, how missing assessments were handled, or whether every eligible event was captured. Those details are not reported in the registry record.

What do the planning illustrations represent?

The record describes sample-size calculations as planning illustrations based on the observed effect, rather than as the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to a stated fraction of the observed effect. For time-to-event outcomes, the description says calculations use the total number of events; for other outcomes, they use participants per arm. These assumptions describe the illustrations, not the single-group study design, and do not establish that the trial had a randomized two-arm analysis.

A planning sample size estimates the amount of information a future study might need under chosen assumptions. It is not observed power, and it does not demonstrate that the study detected an effect. The actual illustration values and the observed primary endpoint effect are not reported in the registry record. The registry record also does not report a sample-size justification used to design this trial.

Why can over-dispersion matter?

In general, over-dispersion means that observed variation exceeds what a statistical model assumes. It is especially relevant to models for counts or repeated observations when outcomes vary more across participants or settings than a basic model allows. Accounting for over-dispersion can affect estimated uncertainty and confidence intervals. The primary endpoint in this study is a binary participant-level count, not a reported repeated count outcome. The registry record does not state that an over-dispersion model was used or describe another statistical model for the primary endpoint. No particular model should therefore be attributed to this analysis.

The record lists one analysis entry, but does not report its estimator, analysis population details beyond the primary endpoint description, missing-data method, or inferential procedure. The methods that can be described with confidence are thus limited to the endpoint definition, the independent adjudication, the single-group design, and the stated planning-illustration assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary composite endpoint and five secondary outcomes: Flow Reversal System Technical Success, Flow Reversal System Success, Stent Success, Clinical Success, and Patency at 30 Days. It records six outcome measures overall and one analysis entry. The statistical plan for the primary and secondary outcomes, including any adjustment for multiple testing, is not reported in the registry record.

Multiplicity is a general concern when several outcomes or comparisons are tested. The more questions examined, the greater the chance that at least one apparently notable finding could arise by chance if results are interpreted without accounting for the number and relationship of tests. Whether an adjustment is needed depends on the aims and analysis plan. The outcome list alone does not show that all outcomes were tested, that they shared an inferential family, or that a particular correction was used. No multiplicity procedure or hierarchy beyond the non-hierarchical primary composite description is reported.

The primary endpoint population is stated as all primary endpoint evaluable subjects. The number evaluable, participant flow, extent of missing outcome data, and handling of missing assessments are not reported in the registry record. It is also not reported whether participants with incomplete follow-up were excluded, imputed, or handled by another method. These omissions limit assessment of how the analysis population may differ from enrollment.

The record's safety denominators are reported separately for serious and other adverse events, but the primary endpoint denominator is not. No assumption should be made that these populations are identical. The registry record does not report interim analyses, stopping rules, or a detailed statistical analysis plan. Their presence or absence cannot be inferred from the completed status or the number of analysis entries.

11. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypotension (5.7%), stroke/cerebrovascular accident (cva) (2.0%), other (other) (2.0%), anemia (1.6%), arrhythmia (1.6%).

For the GFRS Pivotal Subjects group, the registry record lists 40 participants affected under serious adverse events and 62 under other adverse events, with 245 at risk for each category. These are safety summaries, not the primary composite major adverse event result. The record does not report how serious and other adverse events were defined for these summaries or how they overlap with the independently adjudicated endpoint.

The listed serious adverse-event terms and percentages are Hypotension, 5.7%; Stroke/Cerebrovascular accident (CVA), 2.0%; Other (Other), 2.0%; Anemia, 1.6%; Arrhythmia, 1.6%; and Other (Cardiac), 1.6%. These entries identify reported terms; they do not provide event counts for the primary endpoint or establish that each term represents a distinct participant. The registry record does not explain whether participants could appear under multiple terms, so the percentages should not be added or treated as mutually exclusive.

Interpretation also depends on the recorded denominator and the way adverse events were collected and classified. The record gives the at-risk denominator for the safety summaries, but does not report follow-up completeness or additional detail about ascertainment. Serious adverse-event figures describe safety reporting; they do not, on their own, establish a causal relationship to the device or provide a randomized comparison.

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

The registry record establishes that this was a completed, single-group Phase 3 study of the GORE Flow Reversal System in carotid artery stenting among subjects at high risk for carotid endarterectomy. It defines a 30-day composite endpoint comprising death, stroke, myocardial infarction, or transient ischemic attack, with events adjudicated by an independent Clinical Events Committee. It also describes comparison with an Objective Performance Criterion derived from distal embolic protection studies.

Those details do not establish the primary endpoint result. The event count, endpoint denominator, rate, uncertainty interval, and numerical benchmark are not reported in the registry record. It is therefore not possible to determine from the recorded details whether the primary endpoint was above, below, or compatible with the criterion, or how precisely any comparison was estimated. The study's enrollment number is not a replacement for the unreported primary endpoint denominator.

The safety summary reports participants affected under serious and other adverse events, alongside serious-event terms and percentages. Those entries provide safety information as recorded, but the registry does not explain their relationship to the primary composite or establish which events were adjudicated as primary endpoint events. Nor does a single-group safety summary isolate the device's causal contribution to an event.

In general, an external benchmark can contextualize observed outcomes, but its usefulness depends on how closely its population, definitions, follow-up, and ascertainment align with those of the study. The benchmark's numerical value and methodological details are not reported in the registry record, so that alignment cannot be assessed. The results described in the record should not be read as a randomized comparison or as proof of benefit or lack of benefit. They support a description of the study design and recorded safety summaries, while the main efficacy and comparative interpretation remain unresolved in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates the distinction between a single-group performance study and a randomized comparative trial. The registry record describes outcomes with the GORE Flow Reversal System and a comparison to an Objective Performance Criterion based on distal embolic protection studies. An external benchmark can be useful for framing performance, but it does not have the same design features as a concurrent randomized control. Interpretation depends on the benchmark's definition and on comparability between its source studies and the present study.

The primary endpoint also illustrates the trade-offs of a composite. Combining death, stroke, myocardial infarction, and transient ischemic attack creates an overall measure of major adverse events within a defined follow-up window. At the same time, an aggregate result can obscure the distribution and relative contribution of individual components. The record identifies independent adjudication and a non-hierarchical endpoint, but does not report the primary result or component counts.

Finally, the record underscores the difference between enrollment and an analysis denominator. It reports enrollment of 245, but defines the primary endpoint population as all primary endpoint evaluable subjects without reporting their number. It separately lists safety denominators. These populations should not be assumed to be interchangeable. Together, the design and reporting details show why a result requires more than an outcome label: the endpoint count, denominator, benchmark, and uncertainty are necessary to interpret the central statistical question.

14. 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 principal limitation for interpretation is that the registry record does not report the primary endpoint count, denominator, rate, or uncertainty interval. Although enrollment is listed as 245, the primary endpoint population is all primary endpoint evaluable subjects, and its size is not reported. The primary outcome's observed frequency and precision therefore cannot be assessed from the recorded details.

The study is single-group, with allocation listed as not applicable and masking listed as none. The summary describes comparison with an external Objective Performance Criterion, but the criterion's value, derivation, and statistical comparison are not reported in the registry record. This prevents assessment of the benchmark's suitability and means that a randomized treatment contrast cannot be inferred.

The primary endpoint components are specified, but their separate results are not reported. The record does not provide detailed definitions for the secondary outcomes or their numerical results. It also does not report participant flow, follow-up completeness, missing-data handling, analysis details, multiplicity procedures, interim analyses, or the statistical plan. These omissions limit evaluation of potential analytic and reporting choices.

The safety summaries contain serious and other adverse-event figures and a list of serious-event terms, but the record does not explain their overlap with the primary composite or whether term categories overlap with one another. These summaries should not be used to reconstruct the primary endpoint. The trial's completed status and listed enrollment do not resolve any of these uncertainties.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: GORE Embolic Protection With Reverse Flow — NCT00594100.
• Registry record last updated 2013-12-27; status last verified 2013-12.
• Results first posted 2009-05-05.
• 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.

18. Record Summary

The registry record describes NCT00594100, GORE Embolic Protection With Reverse Flow, as a completed Phase 3, single-group study sponsored by W.L.Gore & Associates. Enrollment is listed as 245; the study started in 2006-07, with primary completion in 2008-09. The intervention was the GORE Flow Reversal System for embolic protection during carotid stenting.

The primary endpoint was the number of primary endpoint evaluable subjects with one or more major adverse events through the 30-day visit window. The composite included death, stroke, myocardial infarction, and transient ischemic attack, with independent Clinical Events Committee adjudication. The study summary describes comparison with an Objective Performance Criterion derived from distal embolic protection studies.

The primary endpoint result and numerical benchmark are not reported in the registry record. Safety summaries list 40 participants affected under serious adverse events and 62 under other adverse events, with 245 at risk for each. Five secondary outcomes are named, but their results are not reported in the registry record.