Safety and Performance Study of Large Hole Vascular Closure Device: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Performance Study of Large Hole Vascular Closure Device (NCT01943344), a na na study. The primary outcome is Major Vascular Complications Directly Related to Device.

2. Clinical Question

This is a feasibility and safety question, not a comparative treatment-effect question. With no control group, the study can describe outcomes observed among participants who received the device, but it cannot establish how those outcomes compare with another closure method or with no device. The record also lists minor vascular complications directly related to the device as a secondary outcome, without reporting a result for that outcome.

The endpoint concerns complications attributed directly to the device within the stated follow-up window. The record does not provide a numerical estimate of the major complication rate, its uncertainty, or an analysis population denominator for that outcome. It notes that two participants died before 3-month follow-up for reasons not related to the study device and were not included in the primary endpoint analysis. A third participant died before study completion at 12 month follow-up, also not related to the device. Further details about how these events and other missing observations were handled are not reported in the registry record.

3. Trial Design

FRONTIER I is a completed, single-group clinical investigation of the VIVASURE CLOSURE DEVICE™. The registry lists the study phase as NA, allocation as NA, and masking as none. Enrollment was 12. The study began in 2013-07, and primary completion was recorded as 2014-07. These dates describe the registered study timeline; they do not supply results or indicate when every participant completed follow-up.

Participants receiving the device formed the treatment group. There was no randomized allocation and no like-for-like control arm. Accordingly, the study design supports a descriptive assessment of what was observed among device recipients, rather than a randomized estimate of the device’s effect relative to an alternative. Differences from outcomes in other populations or studies would not, by themselves, establish a causal difference because the registry record does not describe a concurrent comparison.

The stated purpose was to gather feasibility data on clinical use in relation to safety and to confirm performance in percutaneously closing femoral arterial puncture sites in the range of 18-24 F after endovascular procedures. The primary endpoint was major vascular complications directly related to the device, defined by VARC-2, up to 3 months of implantation. Minor vascular complications directly related to the device were listed as a secondary outcome.

The registry record lists three outcome measures and no analyses. It does not report the protocol’s detailed methods, the planned statistical analysis, sample-size justification, interim analyses, or criteria for deciding whether feasibility or performance targets were met. These details should not be inferred from the enrollment or study dates. The record also does not report a numerical primary endpoint estimate, confidence interval, or hypothesis test. Therefore, the design can be described, but its registered outcome information is insufficient to quantify the primary result or its precision.

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: Two subjects died prior to 3-month follow-up, not related to the study device, hence, were not included in analysis. A third subject died prior to study completion (12 month follow-up), not related to the study device.

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 Major Vascular Complications Directly Related to Device, measured over up to 3 Months of implantation.

The primary endpoint is the percentage of participants with major vascular complications directly related to the VIVASURE CLOSURE DEVICE™ up to 3 months of implantation. The description states that major complications are defined by VARC-2. The endpoint is intended to capture clinically important vascular events attributed to the device during the specified period, rather than every event occurring after implantation.

A participant-level percentage is a natural way to summarize a binary outcome: each participant either meets the endpoint definition during the stated follow-up or does not. Such an endpoint can make an observed safety frequency easy to interpret, provided the numerator, denominator, event definition, and follow-up are clear. The registry record specifies the event definition and time frame, but does not report the endpoint numerator, denominator, percentage, or uncertainty interval. It therefore does not establish the observed frequency or how precisely that frequency was estimated.

The record says two participants died before 3-month follow-up, for reasons not related to the study device, and were not included in the analysis. A third participant died before study completion at 12 month follow-up, also for a reason not related to the device. The endpoint description does not explain in detail how other incomplete follow-up or missing endpoint assessments were handled. Deaths and incomplete observations matter because they can affect which participants contribute information to an endpoint measured over time. The registry record does not provide enough detail to reconstruct that analysis population or the primary endpoint estimate.

As a general statistical point, a safety endpoint can identify the frequency of a defined event in the studied group, but a single-group percentage cannot by itself show whether the device caused the event or whether the frequency differs from that under another approach.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-level percentage mean?

For a binary endpoint, each participant is classified according to whether the defined event occurred within the specified follow-up period. A percentage expresses the event frequency among the participants included in the analysis. To interpret it, readers need the event definition, follow-up window, number of participants assessed, event count, and rules for handling missing observations. The registry record defines the primary event and its time frame, but does not report the count, denominator, or percentage. The primary result therefore cannot be checked or interpreted quantitatively from the record.

Percentages describe frequency in the analyzed group; they do not, on their own, show why an event occurred. Attribution to the device is part of the registry’s endpoint definition, but the record does not provide adjudication details or a description of how that attribution was made. The distinction is important: an event occurring after implantation is not automatically an event caused by the device.

What would a confidence interval add?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under the assumptions of the analysis. For a binary-event percentage, it communicates how much uncertainty remains about the underlying event frequency in a population similar to the studied participants. It is not a guarantee that the true value lies within a particular interval, and it does not account automatically for limitations such as selection, incomplete follow-up, or outcome misclassification.

The registry record does not report a primary endpoint confidence interval or the underlying event count and denominator. No interval can therefore be interpreted from this record. A percentage without an uncertainty measure would also be difficult to assess, especially in a small feasibility study, because the apparent frequency may be imprecise.

Why does the single-group design matter?

A single-group study observes outcomes among people receiving the intervention without a concurrent control group. It can describe the experience of the enrolled group and can contribute feasibility and safety information. It cannot separate the intervention’s effect from other explanations for observed outcomes in the way a suitable randomized comparison is designed to do.

Here, allocation is recorded as NA, masking as none, and the model as single group. There is no randomized comparator. Thus, any reported endpoint percentage would be a descriptive outcome among device recipients, not a randomized estimate of how outcomes differ under another treatment. Comparisons with other studies would require caution because populations, procedures, follow-up, definitions, and ascertainment may differ. The registry does not report an adjusted comparison or any analysis of this kind.

How should the follow-up window be read?

The primary endpoint applies up to 3 months of implantation. This defines the period during which the major vascular complication outcome is assessed; it is not the same as the total study duration or every participant’s follow-up. The registry also notes a death before study completion at 12 month follow-up. That longer follow-up reference does not change the primary endpoint’s stated time frame.

The record says two participants died before 3-month follow-up and were not included in the primary endpoint analysis; those deaths were not related to the device. It also says a third participant died before study completion at 12 month follow-up, not related to the device. The registry does not report the complete follow-up status of every participant or how other missing endpoint assessments were treated. These details matter because an analysis restricted to participants with available assessments can differ from one using other missing-data assumptions.

What do the analysis fields tell readers?

The registry lists no analyses. That means the record does not include a reported statistical analysis for the primary outcome, such as an estimate with an uncertainty interval or a hypothesis test. It does not establish that no analysis was ever performed outside the registry; such information is not reported in the registry record. The protocol’s statistical plan, including any planned interim analyses, is also not reported in the registry record.

As a general concept, an analysis plan specifies how outcomes will be summarized and how deviations, missing data, and multiple outcomes will be handled. A prespecified plan can help readers distinguish planned analyses from choices made after seeing results. Since the registry record does not report those details, it is not possible to assess prespecification or reproduce an analysis. The primary result itself is also not reported, so recalculation from posted summary statistics is not possible.

What is the role of sample-size planning?

Sample-size planning asks how much information a proposed study might need for a defined statistical objective under stated assumptions. It is not the same as the number enrolled, and an illustrative calculation based on an observed effect is not the trial’s own design justification. The record’s general planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not evidence that this single-group study used a two-arm design. The record does not report a study-specific sample-size justification or a primary endpoint analysis.

In general, planning calculations depend on assumptions about the effect to detect, variability or event frequency, significance level, power, and design. If those assumptions differ from the eventual study conditions, the resulting planning illustration may not describe the study’s ability to answer its question. Such calculations are not observed power and cannot replace a confidence interval around an actual outcome estimate. No numerical planning results should be interpreted as observed trial outcomes.

Why distinguish statistical from clinical interpretation?

Statistical summaries describe data under an analysis method; clinical interpretation also depends on event definitions, severity, context, and the value placed on outcomes. A statistically precise estimate would not by itself establish device causation or clinical importance, and an imprecise estimate would not prove the absence of risk. In this record, the more basic limitation is that the primary numerical estimate and its uncertainty are not reported. The endpoint description can be explained, but the endpoint’s observed frequency cannot be assessed.

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("Treatment")
n      <- c(10)
events <- c(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  Treatment  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including the primary endpoint of major vascular complications directly related to the device and the secondary outcome of minor vascular complications directly related to the device. It does not report the full outcome list or a statistical plan for controlling or interpreting multiple analyses. A multiplicity strategy is not reported in the registry record.

In general, when several outcomes or statistical tests are examined, the chance of at least one apparently notable result can increase. Prespecified priorities and an appropriate analysis plan help readers understand whether results are confirmatory or exploratory. Because no analyses are listed, the registry record does not show whether any multiplicity adjustment or hierarchy was planned or used. No p-values or endpoint estimates are reported, so there is no set of statistical findings to interpret for multiplicity.

Missing-data handling is also incompletely described. The primary outcome population statement says two participants died before 3-month follow-up for reasons not related to the device and were not included in the primary analysis. A third participant died before study completion at 12 month follow-up, also not related to the device. The record does not provide a full account of endpoint availability, the analysis denominator, or methods for handling missing assessments. The number of enrolled participants must not be treated as the primary endpoint denominator without that information.

In general, excluding participants with unavailable outcomes can affect interpretation if their likelihood of having an event differs from that of participants with observed outcomes. Different assumptions for missing outcomes can produce different estimates. The registry record does not report sensitivity analyses or enough detail to assess the impact of missing data. The analysis populations and the statistical handling of deaths beyond the stated exclusion are not reported in the registry record.

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: chronic heart failure (33.3%), cardiac tamponade (8.3%), cardiogenic shock (8.3%), copd (8.3%), septicemia/bacteremia (8.3%).

The adverse-event listing reports a treatment group with 12 participants at risk for serious adverse events and 6 participants affected. For other adverse events, it reports 12 at risk and 0 affected. The record lists Chronic heart failure at 33.3%, and Cardiac tamponade, Cardiogenic shock, COPD, Septicemia/bacteremia, and Renal failure/insufficency at 8.3% each. These are the reported term labels and percentages; the registry entry does not provide additional detail about their timing or relationship to the device.

These figures concern serious adverse events, not necessarily the primary endpoint. The primary endpoint is specifically major vascular complications directly related to the device as defined by VARC-2. The serious adverse event terms should not be assumed to be device-related, vascular, mutually exclusive, or included in the primary endpoint. The registry record does not describe overlap among terms or provide a detailed event-level account.

The record also notes two deaths before 3-month follow-up and a third death before study completion at 12 month follow-up, each described as not related to the study device. These statements do not substitute for the unreported primary endpoint result. The adverse-event listing is descriptive and does not provide a comparison group or an estimate of excess risk.

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

The study is a completed, single-group investigation intended to collect feasibility and safety information about the VIVASURE CLOSURE DEVICE™ for percutaneous closure of femoral arterial puncture sites in the range of 18-24 F after endovascular procedures. Its primary endpoint is clearly described as major vascular complications directly related to the device, defined by VARC-2, up to 3 months of implantation. The registry also lists minor vascular complications directly related to the device as a secondary outcome.

What the registry record does not report is the numerical result for either of these vascular complication outcomes. There is no primary endpoint count, percentage, denominator, confidence interval, or statistical analysis. Therefore, the record cannot establish the observed major-complication frequency, its precision, or whether a study target was met. The absence of a posted result should not be read as evidence that no event occurred.

The adverse-event information provides a separate descriptive account: six participants were reported as affected by serious adverse events, while zero were reported as affected by other adverse events. Several serious-event terms and percentages are listed. The record does not establish that these serious events were caused by the device or that they match the primary vascular endpoint definition. The deaths described in the primary outcome population statement were not related to the device according to the record.

The single-group design also limits what can be concluded. It does not support a randomized comparison with another closure method, and any observed frequency among device recipients would not by itself show what would have occurred under an alternative. The registry record supports understanding the study’s aim, design, endpoint definitions, enrollment, and selected safety reporting. It does not support a conclusion about comparative effectiveness or a quantified primary vascular safety result.

These limits do not erase the value of a feasibility investigation; they define the scope of the evidence available in the registry. More detailed outcome reporting and analysis methods would be needed to assess the frequency and uncertainty of the primary endpoint. The registry record does not report those details.

14. Why This Trial Matters Statistically

Small, single-group feasibility studies can contribute information about whether a device can be used in the intended procedural setting and what outcomes warrant careful monitoring. FRONTIER I addresses a specific context: percutaneous closure of femoral arterial puncture sites in the range of 18-24 F after endovascular procedures. Its stated focus on feasibility, safety, and performance makes the endpoint definition and follow-up window central to interpreting the study.

Statistically, a clearly defined binary endpoint is useful only when readers can also see the event count, analysis denominator, and uncertainty. Those elements are not reported for the primary endpoint in this registry record. The entry therefore illustrates why an endpoint description alone is not enough to judge an observed event frequency. Without the result and its precision, readers cannot distinguish a low observed frequency estimated precisely from a low frequency estimated with substantial uncertainty, or determine whether the event count was zero.

The single-group structure is equally important. It can provide descriptive experience, but it cannot supply a direct randomized comparison. An observed outcome among participants who received the device is not, by itself, an estimate of what the device changes relative to another approach. This distinction helps prevent overinterpretation of feasibility data as comparative evidence.

The entry also highlights the importance of transparent analysis populations. It reports that two participants who died before 3-month follow-up were not included in the primary endpoint analysis and notes a third death before study completion at 12 month follow-up. Without a reported denominator and fuller missing-data methods, readers cannot reconstruct the endpoint analysis. Clear reporting of these elements is essential to understanding which participants contribute to a result.

Finally, the adverse-event listing and the vascular complication endpoint answer different questions unless their definitions and overlap are specified. Keeping those classifications separate supports a more disciplined reading of safety evidence. The registry’s limited outcome reporting makes these statistical distinctions particularly consequential.

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 principal limitation of the available registry information is that it does not report the numerical primary endpoint result. The major vascular complication count, percentage, analysis denominator, and uncertainty interval are absent. The listed secondary vascular outcome also has no reported result. Thus, the study’s stated safety and performance aims cannot be evaluated quantitatively from this record.

The single-group design has no concurrent randomized control. Even if a device-related outcome estimate were available, the design would not provide a randomized comparison against another closure method. The registry lists no analyses, and it does not report an adjustment strategy, a detailed statistical plan, or a study-specific sample-size justification. Interim analyses and the protocol’s approach to hypothesis testing are not reported in the registry record.

Follow-up and analysis-population reporting are incomplete for reconstructing the primary endpoint. The record says two participants died before 3-month follow-up, were not included in the primary analysis, and had deaths unrelated to the device. It also describes a third death before study completion at 12 month follow-up, not related to the device. The endpoint denominator, full outcome availability, and treatment of any other missing observations are not reported.

The serious adverse event listing is not a substitute for the missing primary endpoint. The record does not provide detailed event-level information, timing, overlap among listed terms, or a complete account of attribution to the device. The listed serious-event categories should therefore remain distinct from the primary VARC-2 vascular endpoint.

Additional eligibility criteria, participant characteristics, procedural details, and outcome-adjudication methods are not reported in the registry record. These omissions limit assessment of how broadly the study findings could apply, even if the outcome estimates were available.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Performance Study of Large Hole Vascular Closure Device — NCT01943344.
• Registry record last updated 2018-11-02; status last verified 2018-01.
• Results first posted 2016-07-06.
• 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

NCT01943344, titled Safety and Performance Study of Large Hole Vascular Closure Device, is the FRONTIER I study sponsored by Vivasure Medical Limited. It is listed as completed, with enrollment of 12, a start date of 2013-07, and primary completion in 2014-07. The study is single-group, with allocation recorded as NA and masking as none.

The investigation concerns the VIVASURE CLOSURE DEVICE™ for percutaneous closure of femoral arterial puncture sites in the range of 18-24 F after endovascular procedures. The primary endpoint is major vascular complications directly related to the device, defined by VARC-2, up to 3 months of implantation. Minor vascular complications directly related to the device are listed as a secondary outcome.

The registry record does not report a numerical primary endpoint result, its denominator, or an analysis. It notes two deaths before 3-month follow-up, not related to the device, whose participants were not included in the primary analysis, and a third death before study completion at 12 month follow-up, also not related to the device. Serious adverse event terms and percentages are listed separately.