Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot (NCT04265807), a randomized na study. The primary outcome is Attrition.

2. Clinical Question

The study rationale concerns possible reperfusion injury after restoration of blood flow following cardiac arrest. The registry describes remote ischemic conditioning as intermittent application of a device, such as a blood pressure cuff, to a limb to induce non-lethal ischemia. It notes that earlier evidence in animals with cardiac arrest and in humans with acute myocardial infarction had suggested possible effects, while stating that this had not been proven in humans who had experienced out-of-hospital cardiac arrest. The pilot therefore focused on feasibility of applying the intervention in the emergency department rather than establishing a clinical benefit.

The primary result concerns whether participants completed their assigned intervention, not whether remote ischemic conditioning changed cardiac injury, function, survival, or another clinical outcome. Those outcomes appear among the secondary outcomes, but the registry results available for interpretation are limited. In particular, results for several listed secondary outcomes are not reported in the registry record. The clinical question should therefore be read as a feasibility question in a small randomized study, with selected secondary measures offering exploratory context rather than a definitive test of efficacy.

3. Trial Design

The RICE pilot is described as a single-center, randomized, double-masked, parallel-group study of active remote ischemic conditioning versus sham remote ischemic conditioning. The registry lists the phase as NA and the status as completed. Enrollment was 30 participants. The registry lists 16 participants in the intervention group and 14 in the control group for the primary outcome. The study start date was 2020-07-01, and primary completion was 2022-02-03.

Participants were described as patients resuscitated from out-of-hospital cardiac arrest and transported to hospital. The intervention was intended for application after emergency department arrival. For the active group, the registry describes a standard non-invasive blood pressure cuff and a disposable plastic clamp, and specifies three cycles of inflation-deflation as the intended duration. The sham package was described as identical in size, weight, and appearance to the active package. Further details about the active cycles and the sham procedure are not reported in the registry record; the arm descriptions are incomplete.

Random allocation and double masking can reduce some sources of bias in a comparison, but the registry does not report the allocation sequence method, who was masked, or how masking was maintained or assessed. Eligibility criteria, recruitment procedures, and the exact treatment timing are also not reported in the registry record. These omissions make it difficult to judge how participants were selected or how closely the intervention could be delivered as intended in other settings.

The primary outcome was attrition, defined as the proportion of randomized subjects who did not remain on allocated therapy for the intended duration. That duration was completion of three inflation-deflation cycles, assessed at intervention completion, an average of 30 minutes from enrollment. Secondary outcomes included treatment success, cardiac function, cardiogenic shock, STEMI, myocardial injury, renal dysfunction, hospital-free survival, and withdrawal of care. The record lists 20 outcome measures and 13 posted secondary outcomes. Numerical results are available for only selected secondary measures in the registry record. A formal statistical analysis plan, sample-size justification, and interim-analysis details 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

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 Attrition, measured over Completion of their allocated study intervention, an average of 30 minutes from enrollment.

Attrition was the primary endpoint. It was defined as the proportion of randomized participants who did not remain on their assigned therapy for the intended study duration. For this study, remaining on therapy meant completing three inflation-deflation cycles. The outcome was assessed when the allocated intervention was completed, an average of 30 minutes from enrollment.

This endpoint addresses a practical feasibility question: whether the intervention could be delivered for its intended duration to patients in the emergency department after resuscitation from out-of-hospital cardiac arrest. A feasibility endpoint is useful in a pilot because it can identify whether treatment delivery is possible within the study setting and whether participants stop or otherwise fail to complete the assigned procedure. It does not, by itself, measure biological effect or patient benefit.

The registry reports zero participants with attrition in the intervention group and zero in the control group. The corresponding group sizes were 16 and 14. Thus, the posted primary outcome records no observed failure to complete the allocated intervention in either group. This finding is specific to the recorded endpoint and the participants enrolled. It should not be interpreted as evidence that every aspect of treatment delivery was feasible, or that the intervention affects cardiac or neurological outcomes. Measures of intervention fidelity beyond cycle completion are not reported in the registry record.

7. Results Posted in the Registry

• Intervention Group: 0.0% (0/16) versus 0.0% (0/14) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Cardiac Function

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Intervention Group: mean 48.40 versus 51.70 on control; difference -3.30 (95% CI -17.53 to 10.93), standardized effect d = -0.19; z-test p = 0.650.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intervention Group and the control. The interval gives the range of effects that remain compatible with the data.

Proportion With Cardiogenic Shock, %

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Intervention Group: 81.2% (13/16) versus 78.6% (11/14) on control; risk difference 2.7 percentage points (95% CI -26.1 to 31.4), risk ratio 1.03 (0.72–1.48); unadjusted two-proportion z-test p = 0.855.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intervention Group and the control. The interval gives the range of effects that remain compatible with the data.

Myocardial Injury

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Intervention Group: mean 3.70 versus 7.40 on control; difference -3.70 (95% CI -14.28 to 6.88), standardized effect d = -0.30; z-test p = 0.493.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intervention Group and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes provide exploratory context beyond the feasibility-focused primary endpoint. Their estimates do not point uniformly in one direction: the continuous outcomes and the event outcome do not form a consistent pattern that would independently reinforce a clear intervention effect. The associated intervals are broad and include no difference. The unadjusted p values likewise do not provide strong evidence against a no-difference model, but they should not be treated as definitive tests in this setting.

This secondary pattern does not change the interpretation of the primary finding. The primary outcome records no attrition in either group, which is evidence about completion of the assigned procedure as defined in the registry. It is not a surrogate for cardiac function, myocardial injury, or other clinical outcomes. A participant can complete the intervention without that fact answering whether the intervention affects those outcomes. Conversely, uncertainty in the secondary comparisons does not negate the recorded completion result.

The registry lists a broader set of secondary outcomes, including treatment success, STEMI, renal dysfunction, hospital-free survival, and withdrawal of care. Numerical results for several listed outcomes are not reported in the registry record. Consequently, the posted secondary results represent only part of the outcome set, and the overall pattern cannot be fully assessed from the reported numerical results.

Unadjusted secondary results carry less weight because multiple outcomes create multiple opportunities for apparently notable findings by chance. No multiplicity adjustment or hierarchy for secondary outcomes is reported in the registry record. The absence of an adjustment does not automatically invalidate descriptive comparisons, but it means individual secondary p values should not be treated as confirmatory. The varying numbers of participants across measures and the absence of reported analyses further limit interpretation. These outcomes are best regarded as signals for future study design, not as evidence that establishes a clinical effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Treatment Success
• Cardiac Function
• Proportion With Cardiogenic Shock, %
• STEMI
• Myocardial Injury
• Renal Dysfunction
• Hospital Free Survival
• Withdrawal of Care

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a binary participant-level measure: each randomized participant either did or did not remain on allocated therapy for the intended duration. The registry operationalizes completion as finishing three inflation-deflation cycles. Counts and group sizes are the natural way to describe such an endpoint. A risk is the proportion of participants in a group who experience the event; a risk difference subtracts the control-group risk from the intervention-group risk. A risk difference of zero means the observed proportions are equal. In this record, no attrition events were reported in either group, so the posted point estimate is 0.0.

A confidence interval describes a range of values compatible with the data and the method used to calculate it. It is not a guarantee that the true effect lies within the interval, and its interpretation depends on the calculation and study assumptions. With no events in either group, the reported primary interval runs from 0.0 to 0.0. That degenerate interval reflects the observed counts under the calculation used; it should not be mistaken for evidence that the underlying attrition difference is known without uncertainty. General statistical methods for rare or absent events may use approaches that yield non-degenerate intervals, but the registry record does not report such an analysis for this endpoint.

The continuous secondary outcomes are summarized by group means and standard deviations. A mean describes the average observed value, while a standard deviation describes the spread of participant values around that average. The mean difference compares the intervention-group mean with the control-group mean. Cardiac function is reported as percent of left ventricular ejection fraction, and myocardial injury is reported as peak serum troponin level. The uncertainty intervals for both mean differences include values on either side of no difference, so the posted estimates are not precise enough to establish a clear direction of effect.

For the binary secondary outcome of cardiogenic shock, the result is summarized as a risk difference, with a confidence interval and an unadjusted p value. A p value describes how unusual data at least as incompatible with a specified no-difference model would be under that model and the analysis assumptions. It is not the probability that the no-difference model is true, nor does it measure clinical importance. The posted p value is unadjusted, and the registry does not report a multiplicity plan or a formal analysis plan. It should therefore be interpreted cautiously, particularly among multiple outcomes.

The record also contains planning illustrations based on observed secondary effects. These are not observed power calculations and do not indicate the probability that this completed study detected an effect. They illustrate the participants per arm that would be needed under stated assumptions to detect a chosen fraction of an observed effect at 80% or 90% power. For example, planning for 100% of the observed cardiac-function effect gives 416 participants per arm for 80% power and 557 for 90% power. Planning for 75% of the observed cardiogenic-shock effect gives 6,321 participants per arm for 80% power and 8,461 for 90% power. These are planning illustrations, not recommendations or protocol requirements. The registry says the illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own sample-size assumptions and justification are not reported in the registry record.

Over-dispersion is a general concern when event counts vary more than a simple statistical model expects. If it is present and ignored, uncertainty can be understated. The registry does not report an over-dispersion assessment, and the available outcomes do not justify adding such a model after the fact. Similarly, the record does not describe covariate adjustment, repeated-measures methods, or handling of time-to-event outcomes. Those methods should not be assumed to have been used.

The comparison results are unadjusted. No analyses are listed as reported in the registry record, and the reported analyses do not specify a model or adjustment strategy. The study’s randomized design supports a group comparison in principle, but randomization alone does not resolve uncertainty from small groups, incomplete outcome availability, or multiple endpoints. For secondary outcomes, the available data and broad intervals mean that the point estimates should be read as descriptive estimates rather than definitive evidence.

The registry reports outcome-specific sample sizes. Such differences may arise for several reasons, including whether a measure was collected or available, but the reasons in this study are not reported in the registry record. This matters because a comparison using fewer observations may be less precise and may reflect a subset of participants rather than the full randomized groups. The primary outcome and the secondary outcomes should therefore be understood according to their own reported group sizes, without assuming a common analysis population.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate an effect. The primary result has a point estimate of 0.0 for the risk difference and a posted interval from 0.0 to 0.0. Although this interval has no width, the observed event pattern was zero attrition in both groups, with 16 intervention participants and 14 control participants. A zero-width interval in that setting does not capture the uncertainty about the event rate in a wider population. It is a limitation of interpreting the interval from these event counts, not evidence of exact equivalence between the groups.

The secondary confidence intervals give a more visible indication of uncertainty. The interval for cardiac function runs from -17.53 to 10.93; for cardiogenic shock, from -0.261 to 0.315; and for myocardial injury, from -14.28 to 6.88. Each spans the no-difference value and allows effects in more than one direction. These intervals do not establish that the groups are the same. Rather, they indicate that the data are compatible with a range of possible differences, including no difference.

The observed group sizes for these outcomes are small, and the secondary outcome sample sizes vary. In general, limited observations tend to produce less precise estimates, although precision also depends on the variability of the measure and the analysis method. The registry record does not report a formal precision target or a planned clinically important difference. Without those benchmarks, the intervals can be described statistically but cannot be judged against a prespecified threshold for importance.

The posted intervals should be interpreted as unadjusted comparisons. They do not account for the fact that multiple outcomes were assessed, and the registry record does not report a multiplicity strategy. The intervals also do not address whether missing outcome data could have affected the estimates; reasons for the varying outcome sample sizes are not reported in the registry record. Taken together, the available estimates are too imprecise to support strong conclusions about secondary effects.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists 20 outcome measures and 13 posted secondary outcomes, while numerical results are available for only selected secondary measures. No multiplicity adjustment, primary-secondary hierarchy beyond the designated primary endpoint, or prespecified strategy for interpreting secondary tests is reported in the registry record. When several outcomes are examined, some results can appear unusual by chance even if there is no underlying effect. General statistical practice addresses this issue by defining which comparisons are confirmatory and, when appropriate, adjusting inference or treating other results as exploratory. The registry record does not state that such steps were taken.

The record lists no reported analyses. It does not report a statistical analysis plan, the analysis model for the posted comparisons, or whether any covariate adjustment was planned. It also does not report interim analyses. These details cannot be inferred from the randomized, double-masked design or from the numerical summaries. The posted secondary p values are unadjusted, so they do not account for examining multiple outcomes.

Outcome-specific sample sizes vary. For example, the primary endpoint includes 16 participants in the intervention group and 14 in control, while the reported secondary measures have smaller or different group counts. Reasons for unavailable observations, whether they reflect missing data, non-collection, or another cause, are not reported in the registry record. The extent and handling of missing data therefore cannot be evaluated. No imputation method or sensitivity analysis is reported.

The registry does not specify an intention-to-treat analysis population, a per-protocol population, or another analysis population for the secondary comparisons. The primary endpoint is defined among randomized subjects, but the posted summaries alone do not establish how all randomized participants were handled for every outcome. This absence of detail limits assessment of whether the comparisons preserve the original randomized groups and whether results could be sensitive to missing outcomes or exclusions.

13. 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 lists serious adverse events for 0 of 16 participants in the intervention group and 0 of 14 in the control group. It lists other adverse events for 1 of 16 participants in the intervention group and 0 of 14 in the control group. Deaths are recorded separately: 9 in the intervention group and 8 in the control group. These figures should be read as registry event counts, not as evidence that an event was caused by or prevented by the assigned device.

The record does not provide event descriptions for the serious-event category, and no top serious-event terms are listed. It does not report the timing, causes, or relationship to the intervention for the deaths in the adverse-event summary. The groups are small, and the counts alone cannot establish comparative safety or explain why events occurred. The serious-event counts of zero also do not demonstrate that serious events could not occur in a larger population. Interpretation is limited to the categories and counts recorded in the registry.

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

The primary result means that the registry records no participant as failing to complete the allocated intervention for the intended duration. Completion was defined as finishing three inflation-deflation cycles, and the assessment occurred at intervention completion, an average of 30 minutes from enrollment. This is a direct description of the feasibility endpoint in the enrolled groups.

It does not mean that the true attrition risk is zero, that the intervention and sham are equivalent, or that every operational aspect of delivery was successful. The posted primary interval of 0.0 to 0.0 is not a precise exclusion of other possible differences when no events were observed. The small study offers limited information about how often attrition might occur among a larger or different group of patients.

The secondary results do not establish an effect on cardiac function, cardiogenic shock, or myocardial injury. Their uncertainty intervals include no difference and allow a broad range of possibilities. Results for several other listed secondary outcomes are not reported in the registry record. These limitations mean that the trial cannot resolve whether remote ischemic conditioning changes clinical outcomes after out-of-hospital cardiac arrest.

The findings also do not prove that no effect exists. A small study with imprecise comparisons may be compatible with multiple possible effects. Nor do the recorded adverse-event and death counts establish causality or comparative safety. They are descriptive registry counts without reported attribution details or a reported inferential safety analysis.

The appropriate scope of interpretation is therefore narrow: the registry documents completion of the intended procedure among participants recorded for the primary outcome, while providing limited and imprecise exploratory information on selected secondary outcomes. It does not provide a definitive clinical effectiveness result or a comprehensive assessment of safety.

15. Why This Trial Matters Statistically

This pilot matters statistically because it separates feasibility from clinical effectiveness. In a setting where an intervention must be delivered soon after resuscitation, whether participants complete the assigned procedure is a practical question. The primary endpoint gives a concrete operational definition of completion: finishing three inflation-deflation cycles. Recording no attrition in either group is informative about that endpoint in this study, even though it cannot by itself answer whether the procedure changes clinical outcomes.

The study also illustrates why a point estimate and its apparent precision must be interpreted together. The primary risk difference is zero, and its reported interval has zero width because no attrition events were observed in either group. Treating that interval as proof of no uncertainty would overstate what a small set of event-free observations can establish. Secondary outcomes make the limits of precision more apparent: their intervals allow a range of effects, and the group counts are modest.

The registry’s planning illustrations demonstrate how sample-size planning depends on the effect selected for detection and on assumptions such as significance level, allocation, and the approximation used. Those illustrations are based on observed effects and are not the trial’s own design justification, nor are they observed power. Their relevance is methodological: an estimate from a small pilot can be unstable, and planning directly from it can produce very different projected sample sizes depending on the chosen fraction of that estimate.

Finally, the registry record leaves important analysis details unreported, including the statistical plan, missing-data handling, and multiplicity strategy. Recognizing these gaps is part of sound interpretation. The study can contribute feasibility information and exploratory estimates, while leaving substantial uncertainty about clinical effects and the methods needed for a confirmatory comparison.

16. 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 trial enrolled 30 participants at a single center, limiting the amount of information available for both the primary and secondary outcomes. The primary outcome had no observed attrition events in either group, so its point estimate is uninformative about the range of attrition rates that might occur in a broader population. Its posted zero-width interval should not be taken as evidence of exact equality.

The primary endpoint captures completion of the allocated intervention, not the quality of delivery, biological response, or patient-centered outcome. The registry’s intervention descriptions are incomplete, and detailed procedural information for the sham group is not reported in the registry record. Eligibility criteria and additional recruitment details are also not reported, limiting assessment of how representative the enrolled participants may be.

Numerical results are available for only selected secondary outcomes. Outcome-specific sample sizes vary, and the reasons are not reported in the registry record. The record does not describe missing-data handling, the analysis population for each comparison, or sensitivity analyses. This makes it difficult to determine whether the varying counts could affect the estimates.

The registry lists no reported analyses and does not report a formal statistical analysis plan, multiplicity strategy, interim-analysis details, or sample-size justification. The secondary comparisons are unadjusted and exploratory. Their broad intervals and small group counts limit precision, while the absence of a reported multiplicity approach reduces the weight that should be placed on individual secondary tests. Finally, the adverse-event summary gives counts without event descriptions or attribution details, so it does not support a causal safety comparison.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot — NCT04265807.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2025-02-04.
• 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.

20. Record Summary

The RICE pilot is a completed, randomized, double-masked, parallel-group, single-center study of active versus sham remote ischemic conditioning after out-of-hospital cardiac arrest. Enrollment was 30, with 16 participants in the intervention group and 14 in control for the primary endpoint. The primary outcome was attrition, defined by failure to complete three inflation-deflation cycles. No attrition was recorded in either group.

Selected secondary results are reported for cardiac function, cardiogenic shock, and myocardial injury. Their unadjusted comparisons are imprecise, and the registry record lists no reported analyses. Several listed secondary outcomes have no numerical results reported in the registry record. Details of the statistical plan, missing-data handling, and multiplicity strategy are also not reported. The results are most informative as a record of intervention completion, with limited exploratory information about clinical outcomes.