Cerebral Protection in Transcatheter Aortic Valve Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cerebral Protection in Transcatheter Aortic Valve Replacement (NCT02214277), a randomized na study. The primary outcome is Reduction in Median Total New Lesion Volume in Protected Territories Between Test and Control Arms as Assessed by DW-MRI at Day 2-7 Post-procedure..

2. Clinical Question

The endpoint concerns new diffusion-positive brain lesions after TAVR, relative to pre-procedure MRI. The protected territories are those uniquely perfused by the vessels protected by the Sentinel System: the left and right carotid arteries and the right vertebral artery. The registry also lists captured-debris histopathology as an observational secondary outcome. The clinical question is therefore specific to an imaging measure in designated vascular territories; it is not, by itself, a measure of every possible neurological outcome or of overall clinical benefit.

3. Trial Design

The SENTINEL Study, NCT02214277, is listed as a randomized, double-masked, parallel-group trial. Its status is completed, and the registry lists enrollment of 363. The study concerns cerebral protection during TAVR in people with severe symptomatic calcified native aortic valve stenosis. The intervention is the Sentinel System with TAVR; the comparator is TAVR. The registry lists the phase as NA.

The primary outcome compares total new lesion volume in protected territories between the Test and Control Arms. It is assessed by diffusion-weighted MRI at Day 2-7 post-procedure. The registry defines total new lesion volume as the sum of diffusion-positive new cerebral lesions on post-TAVR scans relative to pre-TAVR scans. The primary population is described as ITT with imputation. The reported endpoint summaries include 121 participants in the Test Arm and 119 in the Control Arm.

The safety information uses a Safety Cohort combining the Test and Safety Arms, as well as a separate Control Arm. The registry reports 244 participants at risk in the combined Safety Cohort and 119 in the Control Arm for the listed safety summaries. These group definitions differ from a direct Test-versus-Control comparison: the combined safety group is not simply the Test Arm. The record does not give further detail about the Safety Arm’s treatment or its contribution to the combined group.

The registry lists Claret Medical as sponsor. The study start is recorded as 2014-09, and primary completion as 2016-03. It lists three outcome measures, including the primary MRI measure and the observational secondary outcome of captured-debris histopathology. The registry record does not describe the recruitment process, masking roles, site structure, or detailed allocation procedures.

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: ITT with Imputation. Test Arm compared to the Control Arm.

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 Reduction in Median Total New Lesion Volume in Protected Territories Between Test and Control Arms as Assessed by DW-MRI at Day 2-7 Post-procedure., measured over Day 2-7 Post-Procedure.

The primary endpoint is median total new lesion volume in protected brain territories, measured by diffusion-weighted MRI at Day 2-7 after the procedure. The registry defines the volume as the sum of all new diffusion-positive cerebral lesions on the post-TAVR scan relative to the pre-TAVR scan. The protected territories are those uniquely perfused by the left and right carotid arteries and the right vertebral artery.

Diffusion-weighted MRI is used to identify areas of restricted water movement that are treated in this endpoint definition as new cerebral lesions. Measuring volume gives a way to characterize the extent of imaging-detected lesions, rather than counting only whether a participant had any lesion. Restricting the endpoint to protected territories aligns the measurement with the vessels the Sentinel System is intended to protect. These are general reasons why such an imaging endpoint may be informative; they do not establish that an imaging difference corresponds to a difference in symptoms or longer-term outcomes.

The registry reports the median and interquartile range for each arm. The Test Arm median is 109.1 mm3, with an interquartile range of 36.9 to 379.7. The Control Arm median is 174.0 mm3, with an interquartile range of 39.6 to 469.3. A formal between-arm effect estimate, confidence interval, or test result is not reported in the registry record. The posted summaries therefore describe the observed distributions but do not quantify the uncertainty in the comparative effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous volume measure, summarized by the median and interquartile range. These choices describe the center and spread of the observed values without requiring the outcome to follow a symmetric distribution. General statistical explanation: the median is the middle value when observations are ordered, while the interquartile range spans the central half of the distribution. This can be useful when a measure has a long upper tail or unusually large values, because the median is less influenced by extreme observations than the arithmetic mean. The registry does not report a mean or standard deviation for this endpoint.

The registry reports the Test Arm median as 109.1 mm3, with an interquartile range of 36.9 to 379.7, and the Control Arm median as 174.0 mm3, with an interquartile range of 39.6 to 469.3. These summaries convey the observed arm distributions, but they are not a complete comparative analysis. General statistical explanation: uncertainty in an estimated group contrast is commonly described with a confidence interval, which gives a range of values compatible with the data and the chosen method. The registry record does not report a confidence interval or another uncertainty measure for the between-arm comparison. The interquartile ranges are not confidence intervals for the medians or for the difference between arms.

Randomization is intended, in general, to reduce systematic differences between groups at baseline by assigning participants by chance. The record identifies the allocation as randomized, but does not describe the randomization sequence, concealment procedure, stratification, or balance of baseline characteristics. Double masking is also listed. The record does not identify which people were masked or describe how masking was maintained. These omissions prevent a detailed assessment of how the design was implemented.

The endpoint population is described as ITT with imputation. General statistical explanation: an intention-to-treat approach aims to preserve comparison according to randomized assignment, even when participants do not follow the assigned intervention exactly. Imputation is a family of methods for handling missing values by replacing or estimating values under specified assumptions. The exact imputation method, the amount and pattern of missing MRI data, and the assumptions used are not reported in the registry record. Those details matter because conclusions can depend on why measurements are missing and how missing outcomes are handled.

The endpoint is measured at Day 2-7 post-procedure, with total new lesion volume defined by comparison of post-TAVR and pre-TAVR diffusion-weighted MRI. The record does not describe image acquisition procedures, image reading, reader masking, lesion adjudication, or quality control. Such details can affect measurement consistency. The record also does not report whether the primary comparison used a model, a rank-based test, a transformation, covariate adjustment, or another analysis method. It does not identify the estimate targeted by the analysis beyond the stated comparison of medians in the ITT-with-imputation population.

General statistical explanation: when outcome variability is greater than a model assumes, over-dispersion can make standard errors too small and confidence intervals too narrow if the analysis does not account for that variability. For skewed or irregular outcomes, the chosen model and its assumptions should fit the data structure. The use of medians and interquartile ranges offers a descriptive view of the distributions, but it does not reveal which inferential method, if any, was used. No such method or diagnostic assessment is reported for this endpoint.

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. This is a planning illustration, not the trial’s own design calculation and not observed power. No numerical planning sample sizes or fraction values are reported in the registry record. The trial’s own sample-size justification and any prospective power calculation are not reported.

General statistical explanation: power is a design property tied to a specified effect, variability, analysis method, and significance threshold. Retrospective calculations based on an observed effect do not establish whether a trial was adequately designed, and they should not be interpreted as the probability that a result is true. A nonsignificant result, if one were reported, would not by itself establish equivalence or absence of an effect. For this study, no primary p-value or confidence interval is reported, so the precision and inferential outcome of the comparison cannot be assessed from the registry summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies captured-debris histopathology as an observational secondary outcome. It does not provide a detailed statistical analysis plan, a hierarchy of outcomes, or a strategy for controlling multiplicity. Multiplicity arises when several outcomes, time points, subgroups, or tests are examined: the more comparisons considered, the greater the chance that at least one appears notable by chance. Whether that concern applied to the planned analyses cannot be assessed because the plan and analysis details are not reported in the registry record.

The primary population is described as ITT with imputation. The record does not identify the imputation method, the missing-data assumptions, or the number of missing primary MRI measurements. It also does not describe sensitivity analyses that might test whether the primary result changes under different assumptions about missing outcomes. Missing-data handling can affect both the estimated comparison and its uncertainty, so the population label alone is not enough to reproduce or evaluate the analysis.

The registry lists zero analyses. It gives arm-specific primary summaries, but no primary test, confidence interval, adjusted estimate, or detailed analysis population flow. It is therefore not possible to determine from the registry record whether all planned analyses were reported, whether the primary analysis followed a prespecified plan, or whether additional analyses were conducted. Interim analyses and any associated monitoring or stopping rules are not reported.

The record gives no subgroup-analysis plan, covariate-adjustment strategy, or approach to multiplicity across secondary outcomes. These omissions should be treated as unknowns, not evidence that such procedures were absent. Without those details, the posted results can be read descriptively but cannot be fully audited for prespecification, missing-data robustness, or the handling of multiple statistical questions.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stroke (8.4%), death (1.7%), acute kidney injury (0.4%).

The serious adverse event summaries use a combined Safety Cohort (Test plus Safety Arms) and a separate Control Arm. The combined cohort has 244 participants at risk, with 17 affected by a serious adverse event. The Control Arm has 119 participants at risk, with 11 affected. The registry also reports 11 deaths in the combined Safety Cohort and 4 in the Control Arm. These figures are counts within the stated groups; they are not a direct Test-versus-Control comparison because the combined cohort includes the Safety Arm.

The most frequently listed serious adverse event terms are Stroke at 8.4%, Death at 1.7%, and Acute Kidney Injury at 0.4%. These percentages are presented as registry values. The record does not specify the denominator or calculation details for each listed term in the event-term summary, so they should not be used to reconstruct rates or compare groups. It also does not provide event timing, severity grading beyond the serious-event classification, relatedness assessments, or a comparative statistical analysis.

General statistical explanation: adverse-event counts describe what was recorded among participants at risk, but interpretation depends on group definitions, follow-up duration, event ascertainment, and whether participants could experience more than one event. Those details are not reported in the registry record. The figures are descriptive safety information and do not, on their own, establish a causal difference between treatment groups.

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

The posted primary results show a lower median new lesion volume in the Test Arm than in the Control Arm: 109.1 mm3 compared with 174.0 mm3. The corresponding interquartile ranges are 36.9 to 379.7 and 39.6 to 469.3. The outcome is limited to diffusion-positive new lesions in the territories defined as protected, measured by MRI at Day 2-7 after TAVR. These numbers describe the observed endpoint summaries in the stated ITT-with-imputation population.

They do not, by themselves, establish the size or precision of a between-arm effect. The registry record does not report an inferential test, confidence interval, or adjusted comparison for the primary endpoint. Nor do the summaries establish whether any difference in imaging volume corresponds to a difference in neurological symptoms, later function, or another clinical outcome. Those questions require outcome data and analyses that are not reported in this record.

The trial’s stated rationale is that the Sentinel System captures and removes embolic material during TAVR to reduce ischemic burden in the cerebral anterior circulation. A rationale is not a result. The posted MRI summaries address lesion volume in specified territories, not whether the device captured material in every participant or whether an imaging measure translates into clinical benefit.

The safety counts also require care. The registry reports serious adverse events and deaths for a combined Test-plus-Safety cohort and for the Control Arm. Because the intervention-side group combines arms, these data do not isolate the Test Arm for a direct comparison. The event summaries are not accompanied by a comparative analysis or enough detail about timing and ascertainment to support causal conclusions.

In general, a result that is not statistically significant would not prove that treatments are equivalent, and a descriptive difference does not establish a statistically reliable effect. In this case the registry does not report the primary test result at all. The appropriate reading is therefore limited: the arm-specific medians and safety counts are recorded, while the comparative uncertainty and clinical implications remain undetermined from the registry information.

13. Why This Trial Matters Statistically

This trial illustrates the difference between an endpoint summary and an inferential result. The registry reports medians and interquartile ranges for a continuous MRI measure, allowing readers to see the central values and distributional spread in each arm. Yet it does not report a confidence interval, p-value, or other formal estimate for the primary comparison. Descriptive differences and inferential conclusions are distinct; the former do not supply the uncertainty information needed for the latter.

The endpoint also illustrates how the definition of a statistical outcome determines what a result can address. Total new lesion volume is defined through pre- and post-procedure diffusion-weighted MRI, and only lesions in specified protected territories are included. This makes the endpoint closely connected to the intervention’s proposed mechanism, while remaining distinct from a clinical outcome such as symptoms or later function. Statistical precision cannot resolve that distinction: an imaging result and a patient-centered result answer different questions.

The record highlights the importance of transparent methods reporting. An ITT-with-imputation population is named, but the imputation procedure and missing-data details are not reported. The registry identifies randomization and double masking, but does not describe their implementation. It gives no primary analysis method or multiplicity strategy. Without those details, it is difficult to judge reproducibility, assumptions, or robustness.

Safety reporting presents a related lesson: comparison requires compatible groups. A combined Test and Safety cohort is reported alongside the Control Arm, so those counts do not isolate the Test Arm. Group definitions are part of the statistical interpretation, not administrative details. Taken together, the record is useful for identifying the study question and descriptive endpoint and safety summaries, while also showing why transparent comparative estimates and analysis methods are needed for a fuller statistical assessment.

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 registry record leaves key details unavailable for evaluating the primary result. It reports arm-specific medians and interquartile ranges but no comparative estimate, confidence interval, p-value, or named inferential method. The reported summaries therefore do not quantify the uncertainty around a Test-versus-Control contrast. No conclusion about statistical significance, equivalence, or the precision of the effect can be drawn from these summaries alone.

The primary population is labeled ITT with imputation, but the imputation approach, missingness pattern, and number of missing MRI outcomes are not reported. The record does not describe image reading, adjudication, acquisition consistency, or quality control. It also does not report baseline characteristics that would help readers understand the enrolled groups or assess the implementation of randomization.

Masking is listed as double, but the people masked and the procedures used to preserve masking are not reported. Allocation concealment and randomization details are likewise not reported. The trial’s own sample-size justification, statistical analysis plan, interim analyses, stopping rules, and multiplicity approach are not reported in the registry record. The planning illustration described in the record is not the trial’s own design justification.

Safety interpretation has additional limits because the reported non-control group combines Test and Safety Arms. The record does not explain the Safety Arm’s role in enough detail to isolate its contribution to the safety summaries. Event timing, follow-up duration for those summaries, and comparative analysis are also not reported. These limitations concern what can be evaluated from the registry record; they do not establish that the trial lacked procedures or analyses that were not recorded there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cerebral Protection in Transcatheter Aortic Valve Replacement — NCT02214277.
• Registry record last updated 2018-05-11; status last verified 2018-04.
• Results first posted 2018-05-11.
• 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

NCT02214277, titled “Cerebral Protection in Transcatheter Aortic Valve Replacement,” is listed as a completed randomized, double-masked, parallel-group trial sponsored by Claret Medical. The condition is severe symptomatic calcified native aortic valve stenosis, and enrollment is listed as 363. The intervention is the Sentinel System with TAVR, compared with TAVR.

The primary endpoint is median total new lesion volume in protected territories on diffusion-weighted MRI at Day 2-7 post-procedure. The Test Arm median is 109.1 mm3, with an interquartile range of 36.9 to 379.7; the Control Arm median is 174.0 mm3, with an interquartile range of 39.6 to 469.3. The registry does not report a formal comparative estimate or test. Captured-debris histopathology is listed as an observational secondary outcome.

Safety summaries are reported for a combined Test-plus-Safety cohort and the Control Arm. The primary analysis method, missing-data procedures, trial-specific sample-size justification, and multiplicity strategy are not reported in the registry record.