Prehabilitation of Frail Surgical Cancer Patients Using Remote Ischemic Preconditioning: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prehabilitation of Frail Surgical Cancer Patients Using Remote Ischemic Preconditioning (NCT03853473), a randomized na study. The primary outcome is 6 Minute Walk Test Distance (Pre Surgery).

2. Clinical Question

The study also described questions about functional capacity after surgery and intraoperative blood pressure variability. The brief summary states that the investigators hypothesized RIPC might reduce pre-surgical frailty, improve functional capacity four weeks after surgery, and reduce blood pressure variability during surgery. These are hypotheses, not findings. The posted primary outcome is specifically the pre-surgical 6 Minute Walk Test Distance, measured in meters. The record lists additional walking, mobility, grip-strength, and blood-pressure outcomes, but their results are not reported in the registry record.

3. Trial Design

This was a randomized, triple-masked, parallel-group study sponsored by the Medical College of Wisconsin. The registry lists the study as completed, with a start date of 2019-02-22 and a primary completion date of 2023-02-01. Enrollment was 17. The phase is listed as NA. The registry record does not explain which groups of people were masked, how randomization was implemented, or the intended allocation ratio.

Participants were assigned to standard of care or remote ischemic preconditioning. The RIPC arm was instructed to perform the intervention daily at home from enrollment until surgery. The standard-of-care description says that participants received standard of care. No additional description of care in either arm is included in the record summarized for this trial.

The primary outcome was 6 Minute Walk Test Distance (Pre Surgery), measured in meters. It was described as a mean with standard deviation and a pre-surgery timeframe. The posted group summaries include 5 participants in standard of care and 4 in RIPC. The record does not explain why these outcome counts differ from total enrollment, so the reason should not be inferred.

The registry lists 8 secondary outcomes, including pre-surgery mobility and grip-strength measures, post-surgery walking, mobility and grip-strength measures, and intraoperative blood pressure variability. Secondary outcome results are not reported in the registry record. The record also does not report a detailed statistical analysis plan, an interim-analysis plan, or a sample-size justification. The information available therefore supports description of the design and posted primary summaries, but not reconstruction of all trial procedures or analyses.

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.

Before assignment: Participants were consented following their clinical appointments. Group assignment did not occur until after pre-testing, which often occurred on a separate day.

Overall 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.

6. Primary Endpoint

The registry lists the primary outcome as 6 Minute Walk Test Distance (Pre Surgery), measured over Pre-Surgery.

The primary endpoint was the distance participants could walk during a 6-minute walk test in the pre-surgical period. The measurement is reported in meters, with a mean and standard deviation for each randomized arm. The investigators identified the test as a measure of frailty in this pre-surgical population.

As a general explanation, a walking-distance measure summarizes performance on a standardized walking task. It can be useful when a research question concerns physical function, because it records a quantity of walking rather than relying only on a subjective description. In this trial, the endpoint was collected before surgery, so it addresses the investigators’ pre-surgical question. It is not, by itself, a direct measure of surgical outcomes or of the full range of frailty-related characteristics.

The registry reports a mean of 369.0 meters (standard deviation 60.0) for standard of care, based on 5 participants, and a mean of 432.0 meters (standard deviation 42.0) for RIPC, based on 4 participants. These are descriptive group summaries. The registry record does not report a confidence interval, a test statistic, or an inferential comparison for this endpoint. It also does not report a definition of a clinically important difference or a threshold for interpreting individual scores.

The endpoint title specifies the pre-surgery time point. Although the registry lists a post-surgery 6-minute walk outcome among its secondary outcomes, results for that measure are not reported in the registry record. Thus, the posted primary summaries concern pre-surgical walking distance, not postoperative change or recovery.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measurement: distance walked in meters. The registry describes it using a mean and standard deviation. A mean is the arithmetic average of observed measurements in a group. A standard deviation describes how dispersed individual observations are around that group mean. It is not the uncertainty of the mean itself, and it is not a range containing all participants. In general, greater variability makes a group mean less precise when the sample size is unchanged.

What does a mean comparison tell us?

In a randomized two-arm study, a comparison of group means asks whether the average observed outcome differs between the assigned groups. The posted means are 369.0 meters for standard of care and 432.0 meters for RIPC. These summaries describe the participants with reported measurements. A comparison intended to support inference would also need a defined analysis method and an estimate of uncertainty, such as a confidence interval or a test result. The registry record does not report those for the primary comparison.

As a general explanation, a confidence interval expresses the statistical uncertainty around an estimate under the method used to construct it. It is not a guarantee that the true value lies within the interval, nor does it describe the spread of individual participant measurements. Because no confidence interval is reported for the primary comparison, its precision cannot be read directly from the registry record. The standard deviations alone do not substitute for an interval around the between-arm comparison.

Why does sample size matter?

As a general statistical principle, estimates based on fewer observations tend to be less precise, particularly when observations vary. The registry reports endpoint counts of 5 and 4, alongside standard deviations of 60.0 and 42.0 meters. Those small counts warrant caution when interpreting the means as estimates beyond the participants with posted endpoint data. They also mean that the summary values may be sensitive to the measurements of individual participants. The record does not report a sample-size justification, so the intended precision or target detectable effect cannot be established from the registry information.

The study’s total enrollment was 17, but the two primary endpoint counts do not account for all enrolled participants. The reason is not reported in the registry record. No conclusion about exclusions, unavailable measurements, or analysis-set membership should be drawn from the count discrepancy alone. A complete interpretation of a randomized trial usually depends on knowing which participants were included, how outcome data were handled, and whether analysis followed original assignment. Those details are not reported in the registry record.

What does randomization contribute?

As a general explanation, random assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. It does not ensure that groups will be balanced in every small trial. With few participants, chance differences in baseline characteristics can remain. The registry identifies the allocation as randomized, but does not report the sequence-generation procedure, concealment process, or allocation ratio. The posted outcome data alone cannot establish how well the groups were balanced before intervention.

The design is listed as parallel-group and triple-masked. In a parallel-group study, participants are assigned to one arm rather than crossing between interventions as part of the listed design. The record does not identify who was masked or describe how masking was maintained. Therefore, the label should not be expanded into assumptions about masking of participants, clinicians, outcome assessors, or analysts.

How should missing inferential results be read?

The record lists zero analyses and states that values were missing or not estimable for a two-arm comparison of the continuous endpoint. This means the registry does not provide an inferential comparison to accompany the group means. It does not establish that investigators performed no analyses outside the registry record. The statistical analysis plan, model specification, handling of outliers, and any adjustment for baseline values are not reported in the registry record.

As a general explanation, over-dispersion means observed variability is greater than a statistical model assumes. When that occurs, model-based standard errors and intervals can be too small if the extra variability is ignored. The posted standard deviations describe observed spread, but the registry does not report a model or diagnostic assessment, so over-dispersion cannot be evaluated as an issue in an analysis of this endpoint.

The registry also does not report interim analyses, stopping rules, or multiplicity procedures. Those omissions prevent assessment of whether any planned repeated testing or multiple-outcome strategy affected interpretation. No specific method should be attributed to the investigators unless it is reported.

Any sample-size calculations used for planning should be interpreted as planning illustrations, not as observed power. In general, such illustrations depend on assumptions about the effect to detect, variability, allocation, and statistical test. They do not measure the probability that a completed study has demonstrated an effect, and they cannot repair the lack of a reported inferential result. The registry record does not report the trial’s own sample-size justification or enough detail to identify a prespecified design target.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Standard of Care", "Remote Ischemic Preconditioning")
n   <- c(5, 4)
m   <- c(369, 432)
sp  <- c(60, 42)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Standard of Care  5  369.000  60.000  294.500  443.500
CARM  Remote Ischemic Preconditioning  4  432.000  42.000  365.169  498.831

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 secondary outcomes in addition to the primary pre-surgery 6-minute walk measure. These outcomes span pre-surgery mobility and grip strength, post-surgery walking, mobility and grip strength, and intraoperative blood pressure variability. Their results are not reported in the registry record. The record does not describe a multiplicity strategy, such as prioritizing selected comparisons or adjusting inference across multiple outcomes. Without such information, it is not possible to determine how the investigators intended to manage the chance of false-positive findings across multiple statistical tests.

Missing-data handling is also not reported. The primary summaries include 5 participants in standard of care and 4 in RIPC, while total enrollment is 17. The record does not explain why these counts differ or whether any missing outcomes were imputed, excluded, or addressed through another method. The analysis populations are not reported in the registry record, so it is unclear which participants were intended to contribute to each analysis.

The registry’s listing of zero analyses and its note that values were missing or not estimable for a two-arm continuous comparison indicate that an inferential primary comparison is not available in the posted record. That does not establish what analyses may have been conducted outside the registry. The statistical analysis plan, prespecified handling of missing observations, and any interim-analysis plan are not reported in the registry record. These gaps limit evaluation of both the primary result and the broader set of planned outcomes.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts of 0 in each arm. The number at risk for serious adverse events is listed as 6 for standard of care and 6 for RIPC. It reports deaths of 0 in both arms. For other adverse events, the counts are 0 in standard of care and 1 in RIPC; the number at risk is listed as 6 in each arm.

These figures are counts in the registry record, not evidence that an event was or was not caused by the assigned intervention. The record does not provide details about the single other adverse event, its severity, timing, or relationship to treatment. It also does not provide a narrative explaining the adverse-event population or why these risk counts differ from the primary endpoint counts. The at-risk counts should therefore be read as the denominators reported for these safety entries, not assumed to represent the same analysis population as the primary outcome.

With small reported safety groups, absence of a recorded serious event does not establish that the risk of such events is zero. These figures describe what the registry reports for the trial and cannot, by themselves, characterize safety more broadly. Additional adverse-event details are not reported in the registry record.

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

The posted data show descriptive pre-surgical 6-minute walk distance summaries for two randomized arms: 369.0 meters on average for standard of care and 432.0 meters on average for RIPC. The corresponding standard deviations are 60.0 and 42.0 meters. The endpoint counts are 5 and 4 participants, respectively. These are the registry entries that can be read directly from the primary outcome results.

Those summaries do not, by themselves, establish that the groups differ beyond chance variation. The registry record does not report an inferential comparison, confidence interval, or p-value for this continuous endpoint. It also does not report a clinically important threshold. Consequently, neither statistical precision nor clinical importance can be evaluated from the posted primary results alone. The means should not be interpreted as proof that RIPC changed walking distance or frailty.

The trial’s stated hypotheses included postoperative functional capacity and intraoperative blood pressure variability. The registry lists these and other secondary outcomes, but their results are not reported in the registry record. The brief summary’s hypothesis statements should not be treated as observed results. The record also does not report outcomes that would support conclusions about surgical outcomes more broadly.

Interpretation is constrained by the small endpoint counts and the unexplained difference between enrollment of 17 and the 9 participants represented in the primary summaries. No explanation of missing outcome data or analysis populations is reported. Randomization is listed, but the record does not give enough detail to assess allocation procedures or baseline balance. These limitations do not erase the posted descriptive values, but they limit what can be concluded from them.

In short, the registry provides a small-sample descriptive comparison of pre-surgical walking distance, not a reported statistical test of the intervention’s effect. Conclusions about efficacy, postoperative function, blood pressure variability, and safety beyond the listed event counts are not supported by the available registry results.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a randomized design and a fully interpretable statistical result. Randomization is an important design feature, but a reader also needs outcome counts, an estimate of the between-arm contrast, and a measure of uncertainty to assess what the observed data can establish. Here, the registry reports the group means, standard deviations, and endpoint counts, but not an inferential comparison for the primary outcome.

The small endpoint groups make precision especially relevant. A mean can be reported precisely to a decimal place without being estimated precisely in the statistical sense. The standard deviations and participant counts help readers understand the context of each mean, but they do not supply a confidence interval for the difference. The missing inferential result therefore matters to interpretation, not merely to presentation.

The trial also emphasizes why outcome accounting is important. Enrollment is 17, while the posted primary endpoint summaries include 5 and 4 participants. The registry does not explain the difference. Without an account of participant flow, missing measurements, and analysis populations, readers cannot determine how the outcome summaries relate to the randomized groups as a whole.

Finally, the record lists several secondary outcomes and describes hypotheses about postoperative function and intraoperative blood pressure variability, yet their results are not reported. This makes it important to distinguish stated research questions from posted findings. The study is statistically informative as an example of how descriptive results, uncertainty, missing-data reporting, and multiplicity information all contribute to a cautious interpretation of a clinical trial.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary outcome summaries cover only 5 standard-of-care participants and 4 RIPC participants, while enrollment was 17. The registry record does not explain the difference, describe participant flow, or state how missing outcome data were handled. It also does not identify the analysis population. These gaps limit interpretation of how representative the posted summaries are of the randomized groups.

No inferential comparison for the primary endpoint is reported. The registry record provides no confidence interval, p-value, or statistical model for comparing arms, and it does not report a clinically important threshold. The group means and standard deviations therefore support a descriptive account but not a determination of statistical precision or clinical importance.

Details of randomization and masking are limited. The record identifies the study as randomized and triple-masked, but does not describe sequence generation, allocation concealment, the roles masked, or how masking was maintained. Baseline characteristics are not included in the registry record for this record, so balance between arms cannot be assessed from the posted information.

The statistical analysis plan, sample-size justification, interim analyses, multiplicity procedures, and missing-data methods are not reported in the registry record. Eight secondary outcomes are listed, but their results are not reported. The safety entries provide counts but little detail about the other adverse event or the safety population. Together, these limitations leave substantial uncertainty about analysis choices and the scope of conclusions that can be drawn from the available record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prehabilitation of Frail Surgical Cancer Patients Using Remote Ischemic Preconditioning — NCT03853473.
• Registry record last updated 2024-09-19; status last verified 2024-09.
• Results first posted 2024-09-19.
• 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

NCT03853473 is a completed randomized, triple-masked, parallel-group trial sponsored by the Medical College of Wisconsin. Enrollment was 17. It studied daily at-home remote ischemic preconditioning from enrollment until surgery compared with standard of care in frail, elderly patients with colon cancer.

The primary outcome was pre-surgery 6-minute walk distance in meters. The posted mean and standard deviation were 369.0 and 60.0 for 5 standard-of-care participants, and 432.0 and 42.0 for 4 RIPC participants. The registry record does not report an inferential comparison for this endpoint or explain the difference between enrollment and the endpoint counts.

Eight secondary outcomes are listed, but their results are not reported in the registry record. Serious adverse events and deaths are listed as 0 in both arms; other adverse events are listed as 0 for standard of care and 1 for RIPC. Further statistical, missing-data, and safety details are not reported in the registry record.