Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting (NCT01654666), a randomized phase 2 study. The primary outcome is Number of Patients With Cerebrovascular Events, Cardiovascular Events or Death..

2. Clinical Question

3. Trial Design

NCT01654666 is a randomized, double-blind, parallel Phase 2 trial. The registry lists an enrollment of 189 participants and three groups: RIPC, sham RIPC, and control. The RIPC group received standard medical therapy as well as the conditioning procedure. The sham group received standard medical therapy and sham conditioning. The control group received standard medical therapy alone. Carotid artery stenting is the procedure named in the trial and primary-outcome timeframe.

The registry describes RIPC as repeated inflation and release of automated cuffs on both arms. The RIPC cuff pressure is listed as 200 mmHg. The sham description lists a pressure of 60 mmH; that unit is incomplete in the registry wording, so it cannot be clarified from the record. The control group is described as receiving no conditioning procedure.

Random allocation means assignment to groups is intended to be determined by chance. Double masking indicates that the record describes the study as double-blind, but it does not identify which parties were masked or explain how masking was maintained. Those details are not reported in the registry record. Parallel design means the assigned groups are followed as separate groups rather than participants crossing between treatments; this is a general description of the design label.

The primary outcome concerns events within six months after stenting. The primary analysis population is described as participants who fully completed the study, rather than all participants enrolled. Arm-specific flow from enrollment through completion is not reported in the registry record. The record lists serum high-sensitive C-reactive protein, neuron specific enolase, and S-100B, as well as side effects of RIPC treatment, among the secondary outcomes. Detailed result values for those outcomes are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population only included participants who fully completed the study.

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.

Population: Baseline Analysis Population only included participants who finished carotid artery stenting, post-treatment MRI scans and blood drawn.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Cerebrovascular Events, Cardiovascular Events or Death., measured over Within six months after carotid artery stenting.

The primary endpoint is the number of participants with a cerebrovascular event, cardiovascular event, or death within six months after carotid artery stenting. It is a composite endpoint: any participant meeting at least one of the listed event definitions would count as having an event. The cerebrovascular components are ischemic stroke, TIA, cerebral hemorrhage, and hyperperfusion syndrome. The cardiovascular components are angina and myocardial infarction. Death includes death from any reason.

A composite can capture several clinically important types of outcome in one endpoint. As a general statistical consideration, it can also combine outcomes that differ in frequency, severity, or clinical meaning. A total for the composite alone would not show which component contributed most to the result; component-specific results are needed for that distinction. The registry record does not report a primary-outcome count, a comparison between groups, or component-specific primary results.

The record says that the primary analysis included only participants who fully completed the study. This definition matters when interpreting a count: it describes an analysis restricted to completers, not necessarily all participants initially enrolled. The record does not explain how incomplete follow-up, missing endpoint information, or participants who did not complete the study were handled. The endpoint’s timeframe is stated, but the schedule and method for assessing each component are not reported in the registry record.

The endpoint is a participant count, not a measure of time until an event. Counts can describe how many participants met the event definition, while a comparison requires the corresponding group results and a stated analysis. Those primary results and analysis details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to groups by chance. In general, this can reduce systematic differences between groups at the time of assignment, including differences that investigators have not measured. It does not guarantee that groups will be identical, especially in a study of limited size, and it does not by itself address missing outcomes, departures from assigned treatment, or problems with outcome measurement. The registry identifies the trial as randomized but does not report the sequence-generation method, allocation concealment procedures, or details of stratification.

What does double-blind mean in this record?

Double-blind is the registry’s masking designation. As a general concept, masking is intended to reduce the possibility that knowledge of group assignment affects participant behavior, care, or outcome assessment. The record does not say which individuals were masked, how masking was implemented, whether masking was assessed, or whether it remained intact. Because the comparison includes a sham procedure and a no-conditioning control group, these details would help readers understand what the designation means in practice; they are not reported in the registry record.

How should the composite endpoint be understood?

The primary endpoint counts participants with any of several defined cerebrovascular or cardiovascular events, or death, during the stated follow-up window. In general, a composite endpoint can capture more events than a single component and can represent an overall collection of outcomes of interest. Its interpretation depends on the components: a composite may combine events with different frequencies and consequences. A result for the combined endpoint does not tell readers which component occurred or whether the components behaved similarly. Component-level results and a clear account of how events were adjudicated would help interpret a composite, but those details are not reported in the registry record.

What does a participant count show?

A count records how many participants met the event definition in the analysis population. A count alone is not an estimate of a between-group effect unless it is accompanied by the relevant group denominators and a defined comparison. Statistical uncertainty is also important. In general, a confidence interval describes a range of values compatible with the observed data under the analysis assumptions; it gives readers information about precision, not a guarantee that the true effect lies in that range. No primary-outcome confidence interval or inferential comparison is reported in the registry record.

For binary outcomes, statistical analyses commonly compare event proportions or model the chance of an event. The choice of measure and model affects interpretation, and an analysis should account for the trial design and the defined analysis population. These are general principles, not a description of methods used in this trial. The registry record does not report the primary statistical model, effect measure, confidence-interval method, or testing procedure. The primary endpoint is listed as a participant count, and no primary analysis is reported in the registry record.

Why do denominators and analysis populations matter?

The record defines the primary analysis population as participants who fully completed the study. This is a completer-based definition. In general, restricting analysis to completers can make results sensitive to why participants did not complete follow-up, particularly if completion is associated with treatment assignment or outcomes. A flow account and reasons for non-completion help readers assess that risk. The registry record does not report those details or explain how missing endpoint information was handled. The adverse-event entries give separate group denominators, but they do not establish the denominator or analysis population used for the primary endpoint.

How should planning calculations be distinguished from trial results?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability or event frequency, allocation, and statistical testing. It is not an observed treatment effect, and a planning calculation based on an observed effect is not “observed power.” The planning illustration described for this trial uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event examples, the illustration is defined in total events; for other examples, it is defined in participants per arm. Those assumptions describe an illustration, not the trial’s own design justification. The trial’s original sample-size justification is not reported in the registry record. The primary result needed to assess a planning illustration against observed data is also not reported in the registry record.

Why does over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, uncertainty intervals may be too narrow and tests may appear more conclusive than warranted. Different endpoint types require different assumptions, so over-dispersion is not automatically relevant to every analysis. The registry record does not report an analysis of over-dispersion or identify a model for the primary endpoint.

What is not available for evaluating the analysis?

The registry record does not report the primary-outcome analysis, its statistical test, model covariates, handling of multiple comparisons, interim analyses, or missing-data method. These omissions mean readers cannot reconstruct the prespecified analysis or evaluate whether reported results followed it. The record lists no analyses for the outcome information, so statistical significance and precision cannot be assessed for the primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The trial lists a primary endpoint and several secondary outcomes, including serum high-sensitive C-reactive protein, side effects of RIPC treatment, neuron specific enolase, and S-100B. Testing multiple outcomes or comparisons can increase the chance of at least one apparently notable finding by chance. As a general statistical principle, multiplicity procedures can address that issue, but their choice depends on the planned hypotheses and testing strategy. The registry record does not report a multiplicity adjustment, a testing hierarchy, or how the primary and secondary outcomes were to be interpreted together.

The record does not report interim analyses or early-stopping rules. Their use or absence cannot be inferred. It also does not report whether subgroup analyses were planned or conducted. The fact that the trial is randomized does not resolve these questions.

The primary endpoint analysis population is described as participants who fully completed the study. The record does not provide participant flow by group, reasons for non-completion, missing outcome counts, or a method for handling missing data. In general, missingness can affect an estimate when the probability of missing information is related to treatment or outcome. Without information about completeness and the analysis method, readers cannot determine how sensitive the primary result would be to missing data. No primary result is reported in the registry record, so its handling cannot be evaluated empirically.

Enrollment is listed as 189, but the record does not explain how many enrolled participants entered each analysis or how exclusions were handled. The group denominators appearing in the adverse-event entries should not be assumed to be the primary endpoint denominators.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: symptomatic ischemic stroke (3.7%), transient ischemic attack (1.9%), hyperperfusion syndrome (1.8%).

The registry’s serious-event entries list 1 affected participant among 52 at risk in the RIPC group, 3 among 56 in the control group, and 3 among 54 in the sham RIPC group. Its other-event entries list 10 among 52 for RIPC, 26 among 56 for control, and 23 among 54 for sham RIPC. These are counts and denominators as recorded; they do not by themselves establish a causal difference between groups.

The listed serious-event terms are symptomatic ischemic stroke at 3.7%, TIA at 1.9%, and hyperperfusion syndrome at 1.8%. The registry record does not report the denominator or method behind those percentages, so they should be read as posted term-level figures rather than assumed to be group-specific risks. It also does not report event timing, recurrence, severity grading beyond the serious classification, or an inferential comparison of the groups.

Deaths are not listed in these adverse-event entries. That absence should not be interpreted as a confirmed absence of deaths; the registry record does not provide a death count in these entries. These safety figures are distinct from the primary composite endpoint, whose results are not reported in the registry record.

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

The registry record establishes that this was a randomized, double-blind, parallel Phase 2 study of remote ischemic preconditioning around carotid artery stenting. It defines a primary composite endpoint covering cerebrovascular events, cardiovascular events, and death within six months after stenting. It also describes a completer-only primary analysis population and reports selected adverse-event counts.

It does not report the primary endpoint results or an inferential comparison among RIPC, sham RIPC, and control. As a result, the posted information does not establish the direction, size, or precision of any primary-outcome difference. It cannot show whether a difference is compatible with little or no effect, or whether the data are sufficiently precise to distinguish among clinically relevant possibilities. Those judgments require estimates and uncertainty measures that are not reported in the registry record.

The safety counts can be stated descriptively for the denominators shown, but they do not establish that one group had a higher or lower underlying risk. A comparison would need a defined analysis, appropriate uncertainty estimates, and clarity about the population and observation period. The term-specific percentages also lack a reported denominator in the registry record. These limitations prevent interpreting them as direct group comparisons.

In general, a randomized design helps make group comparisons informative, but it does not replace reporting of outcomes, analysis methods, participant flow, and uncertainty. A composite outcome also needs component-level information for a full understanding of what contributed to any overall finding. The registry does not report those primary endpoint results or components.

The trial’s title and rationale describe an investigation of potential neuro-protective and anti-inflammatory effects, with clinical outcomes, serum markers, and brain MRI mentioned in the summary. Those statements describe the study question and rationale, not evidence that the intervention achieved an effect. The registry record does not report results for the primary clinical endpoint or the listed biochemical outcomes. No conclusion about treatment benefit or lack of benefit follows from the information reported.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a registered clinical question and a reported result. The design and endpoint are described: randomized groups, a sham comparison, a standard-care control, and a composite clinical outcome within six months after stenting. Yet the registry record does not include the primary-outcome estimates or a statistical comparison. A clear endpoint definition is necessary for interpretation, but it cannot stand in for the result itself.

The three-group structure also makes the intended comparisons important. RIPC versus sham may address the conditioning procedure against a sham procedure, while comparisons involving control have a different contrast because control received standard medical therapy alone. These are general interpretations of the listed groups, not evidence that the registry specified or tested particular contrasts. The planned comparison strategy is not reported in the registry record.

The completer-only primary analysis population raises a further interpretive issue. Enrollment and the population analyzed are not automatically the same. Without participant flow, reasons for non-completion, and a missing-data strategy, readers cannot assess the relationship between the randomized population and the stated analysis population. This is a general concern when evaluating trial estimates, not proof that bias occurred in this trial.

Finally, the primary endpoint combines several types of event. Such composites can be useful, but readers need both the overall comparison and component-level results to understand what it represents. Neither is reported for the primary outcome. The record therefore illustrates why statistical interpretation depends on transparent reporting of effect estimates, uncertainty, analysis populations, and component outcomes—not only a trial design label and endpoint definition.

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 most important limitation for interpretation is that the registry record does not report primary-outcome results. There is no group-specific primary endpoint count, effect estimate, confidence interval, or p-value in the record. The primary question therefore cannot be answered from the posted information.

The primary analysis population is defined as participants who fully completed the study, but participant flow and reasons for non-completion are not reported. The record does not say how incomplete follow-up or missing endpoint information was handled. It also does not report whether analysis followed assigned groups or how other protocol deviations were treated.

The primary outcome combines multiple cerebrovascular and cardiovascular events with death. Although the component definitions are stated, component-specific primary results and event-adjudication details are not reported. The six-month timeframe is given, but the assessment schedule and ascertainment methods are not described in the registry record.

Further limitations include the absence of a reported statistical analysis plan, planned contrasts, multiplicity strategy, interim analysis information, and original sample-size justification. The double-blind designation is not accompanied by details about who was masked or how. The sham cuff pressure is listed as 60 mmH, an incomplete unit in the registry wording. The serious-event term percentages lack a reported denominator, and the adverse-event entries do not provide inferential comparisons. These gaps limit assessment of both the primary question and the safety figures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting — NCT01654666.
• Registry record last updated 2015-11-11; status last verified 2015-10.
• Results first posted 2015-11-11.
• 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

NCT01654666 is a randomized, double-blind, parallel Phase 2 trial with an enrollment of 189. It compares remote ischemic preconditioning plus standard medical therapy, sham conditioning plus standard medical therapy, and standard medical therapy alone in the context of carotid artery stenting. The primary endpoint is the number of participants with cerebrovascular events, cardiovascular events, or death within six months after stenting. The primary analysis population is described as participants who fully completed the study.

The registry record includes selected serious and other adverse-event counts and lists secondary biochemical and side-effect outcomes. It does not report a primary-outcome comparison, primary effect estimate, or statistical uncertainty. Participant flow, missing-data handling, and detailed statistical methods are also not reported in the registry record.