A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest (NCT01413399), a randomized na study. The primary outcome is Number of Participants Who Survived Up To Hospital Discharge.

2. Clinical Question

The central contrast is the timing of therapeutic hypothermia: initiation during cardiac arrest versus after arrest. The registry describes the study as a pilot and names survival to hospital discharge as the primary outcome. The primary results list 24 participants in the intra-arrest group and 40 in the post-arrest group as surviving to discharge. Group sizes differed, so those counts should be read alongside the numbers assigned to each group rather than as a comparison of raw totals alone.

The clinical question is not equivalent to asking whether either approach is effective compared with no therapeutic hypothermia. Both named groups received a therapeutic hypothermia strategy, and the posted comparison is between those strategies. The record does not include a no-hypothermia group. It also does not report a posted result for every outcome named in the study objective. In particular, a numeric result for survival to admission or neurologic function at discharge is not reported in the registry record.

3. Trial Design

The registry describes a randomized, parallel-group pilot study with no masking. The two groups were intra-arrest therapeutic hypothermia and post-arrest therapeutic hypothermia. The listed intervention is 4 degree chilled saline. The arm descriptions contain no further details. The record lists the study as completed and reports enrollment of 542.

The primary outcome is the number of participants who survived up to hospital discharge. Its timeframe states that participants would be followed for the duration of the hospital stay, with an expected average of 5 weeks. The secondary outcome with posted results is the number of patients who achieve prehospital return of spontaneous circulation; its timeframe describes follow-up during the prehospital course of care, expected to average 1 hour.

For the primary outcome, the intra-arrest group had 208 participants and 24 recorded survivors to discharge; the post-arrest group had 334 participants and 40 recorded survivors. The secondary outcome counts were 76 of 208 for intra-arrest and 90 of 334 for post-arrest. These outcomes have different observation windows and should not be treated as interchangeable measures of the same event.

The study began in 2011-08, and primary completion is listed as 2012-06. The registry identifies Wake Forest University Health Sciences as sponsor. The phase is listed as NA. The original sample-size justification, planned interim analyses, detailed allocation procedures, and full statistical analysis plan are not reported in the registry record. The study's own planning assumptions are therefore not established by the posted information. The sample-size illustrations associated with the posted effects are separate planning calculations, not evidence of the trial's original design.

A randomized comparison can support a more interpretable comparison of assigned strategies than a nonrandomized comparison, but the record does not describe the allocation process in enough detail to assess how it was implemented. With no masking listed, the record does not establish whether participants, clinicians, or outcome assessors were aware of assignment. No additional conclusion about those procedures is warranted from the registry description.

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 Number of Participants Who Survived Up To Hospital Discharge, measured over participants will be followed for the duration of hospital stay, an expected average of 5 weeks.

The primary endpoint is the count of participants who survived up to hospital discharge. It records whether each participant experienced a specified event during the hospital stay, rather than measuring the length of survival or time to discharge. The registry describes follow-up as lasting for the duration of the hospital stay, expected to average 5 weeks.

Survival to discharge is a clinically interpretable outcome because it captures an important status at the end of the reported hospital follow-up. It is also a binary endpoint: each participant is counted as having or not having the event. General statistical explanation: binary outcomes are often summarized as event counts and group-specific event probabilities, then compared using a risk difference, risk ratio, or odds ratio. These measures answer related but not identical questions, so their scale and uncertainty matter when interpreting results.

The posted counts are 24 survivors among 208 participants in the intra-arrest group and 40 among 334 in the post-arrest group. The registry's outcome description refers to an adjusted odds ratio and confidence interval, but a numeric adjusted estimate is not reported in the registry record. The posted comparison summary supplies unadjusted comparison measures. Neurologic function at discharge is named in the study objective, but a result for that outcome is not reported in the registry record. Survival to discharge should therefore not be read as a complete measure of neurologic outcome or longer-term survival.

7. Results Posted in the Registry

• Post-Arrest Therapeutic Hypothermia: 12.0% (40/334) versus 11.5% (24/208) on control; risk difference 0.4 percentage points (95% CI -5.1 to 6.0), risk ratio 1.04 (0.65–1.67); unadjusted two-proportion z-test p = 0.878.

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.

Number of Patients Who Achieve Prehospital Return of Spontaneous Circulation

• 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:
  • Post-Arrest Therapeutic Hypothermia: 26.9% (90/334) versus 36.5% (76/208) on control; risk difference -9.6 percentage points (95% CI -17.7 to -1.5), risk ratio 0.74 (0.57–0.95); unadjusted two-proportion z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Post-Arrest Therapeutic Hypothermia than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry reports one secondary outcome with results: prehospital return of spontaneous circulation. Its unadjusted comparison differs from the pattern for survival to hospital discharge: the secondary risk-difference interval excludes zero and its p-value is 0.018, whereas the primary interval includes zero and its p-value is 0.878. The endpoints reflect different stages of care and different timeframes, so a result for one does not determine the result for the other.

The secondary endpoint may help describe an earlier event in the care course, but it is not a substitute for the primary discharge outcome. Nor does a difference in prehospital return of spontaneous circulation establish a difference in survival to discharge or neurologic function. The registry does not report participant-level transitions between these outcomes, and numeric results for survival to admission and neurologic function at discharge are not reported in the registry record.

Unadjusted secondary findings generally carry less weight than a primary finding because secondary outcomes may be one of several opportunities to observe a nominally notable result. General statistical explanation: when multiple hypotheses are tested, the chance of at least one apparently unusual result can increase if no multiplicity procedure is used. The registry record does not report whether the secondary outcome was part of a prespecified testing hierarchy or whether any multiplicity adjustment was planned. Its result is therefore best read as exploratory evidence within this record, not as independent confirmation of a primary conclusion.

The secondary analysis does not overturn the uncertainty in the primary comparison. The outcomes ask different questions, and the registry does not report analyses that formally combine them. A balanced reading retains both observations: the posted primary comparison is inconclusive about the direction of the group contrast, while the posted secondary comparison shows an unadjusted difference. Neither alone establishes a broad conclusion about the comparative effects of the two strategies.

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

• Number of Patients Who Achieve Prehospital Return of Spontaneous Circulation

9. Statistical Interpretation

10. Statistical Methods Explained

What does a randomized parallel design mean?

Randomized means participants were assigned to study groups by a random process, according to the registry record. A parallel design means the groups were followed as separate groups rather than participants crossing from one strategy to the other. General statistical explanation: random assignment aims to reduce systematic differences between groups at the time of assignment. It does not guarantee that groups will be identical, especially in a pilot study, and the registry description does not supply details about the randomization procedure. The record lists no masking, so it should not be assumed that people involved in care or outcome assessment were unaware of group assignment.

How are the event counts compared?

Both posted outcomes count participants who experienced an event. For discharge survival, the event is survival up to hospital discharge; for the secondary endpoint, it is prehospital return of spontaneous circulation. The group counts are paired with group sizes, allowing a comparison that accounts for the different numbers of participants in the groups. General statistical explanation: a risk difference expresses the contrast between group event probabilities on an absolute scale. A risk ratio compares those probabilities proportionally, while an odds ratio compares event odds. These measures can give different numerical impressions because they use different scales.

The posted primary comparison includes unadjusted risk-difference, risk-ratio, and odds-ratio summaries, as well as an unadjusted p-value. The record's endpoint description mentions an adjusted odds ratio and confidence interval, but the numeric adjusted result is not reported in the registry record. An adjusted and an unadjusted estimate are not interchangeable: adjustment depends on the model and covariates used. Those details are not reported in the registry record, so an adjusted result cannot be reconstructed from the posted information.

What does a confidence interval communicate?

General statistical explanation: a confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method. For a risk difference, zero represents no difference on that scale. If the interval includes zero, the data are compatible with no difference as well as with values on either side of zero. If it excludes zero, the corresponding unadjusted interval indicates that values of no difference are not included under that method. An interval does not give the probability that the true effect lies within its particular bounds, and it does not replace consideration of the size and practical meaning of the estimate.

For the primary result, the interval includes zero; for the posted secondary risk difference, it excludes zero. These are statements about the displayed intervals, not proof of equivalence for the primary endpoint or proof of a clinically important effect for the secondary endpoint. The registry does not state a threshold for a clinically important difference.

How should p-values be read?

General statistical explanation: a p-value measures how unusual results at least as incompatible with a specified null model would be, if that model and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The primary unadjusted p-value is 0.878; the secondary unadjusted p-value is 0.018. These values belong to separate outcomes and do not address the consequences of examining multiple outcomes.

A p-value should be considered with the effect estimate, confidence interval, design, and analysis context. In particular, an unadjusted p-value for a secondary outcome does not account for multiplicity unless an adjustment is reported. No multiplicity procedure is reported in the registry record. Likewise, the record does not report a prespecified hierarchy of outcomes beyond identifying the primary outcome.

Why can over-dispersion matter?

General statistical explanation: over-dispersion means that observed variability is greater than a statistical model expects. It can make standard errors too small if a model assumes less variability than is present, producing intervals that are too narrow and tests that appear more conclusive than warranted. It is especially relevant to count outcomes modeled with assumptions about their variance. The outcomes posted for this trial are participant event counts, and the record does not report a count-model variance or a dispersion estimate. Over-dispersion is therefore a general concept, not a reported feature or documented analysis issue for this study.

What can be inferred from the posted analysis details?

The registry record reports two outcome measures and one posted secondary outcome, but it lists no reported analyses. The displayed comparison summaries allow readers to describe the posted unadjusted results; they do not reveal the full analysis plan, analysis population, missing-data method, or model diagnostics. The registry does not report an interim-analysis plan or explain how sample size was originally justified. Those omissions limit the ability to assess whether the posted results correspond to all prespecified analyses.

General statistical explanation: a pilot study can provide information about feasibility and preliminary estimates, but pilot estimates may be unstable, particularly when event counts are limited. Confidence intervals make that uncertainty visible. The calculated sample-size illustrations based on observed effects are planning scenarios only; they are not a measure of the probability that this trial detected an effect. A trial's design assumptions, such as the effect it was designed to detect, must come from its own planning record, which is not reported in the registry record.

11. Confidence Intervals and Precision

The precision of an estimate is reflected in the range of values compatible with the data under the stated statistical method. For the primary outcome, the posted risk-difference interval includes zero and extends in both directions. This means the data do not pin down the direction of the underlying difference with confidence. The estimate is not precise enough to distinguish a small contrast from no contrast or from a contrast in the opposite direction. The registry does not state what size of difference would be clinically important, so the interval cannot be judged against a stated clinical threshold.

The primary comparison also reports an odds ratio of 1.043, with a confidence interval whose bounds are 0.609 and 1.787. Because those bounds have more than 3 decimal places, they are not repeated. The interval includes the no-association value for an odds ratio, consistent with the uncertainty in the risk-difference comparison. The registry's outcome description refers to an adjusted odds ratio and confidence interval, but a numeric adjusted result is not reported in the registry record; the numeric comparison summary is unadjusted.

The secondary risk-difference interval does not include zero, and its unadjusted p-value is 0.018. That interval gives a more directional unadjusted result for the secondary endpoint, but it does not remove uncertainty about the size or clinical importance of the contrast. It also does not account for the possibility of multiple outcome comparisons. The registry does not report a multiplicity procedure.

General statistical explanation: narrower confidence intervals indicate greater precision, while wider intervals indicate greater uncertainty. Precision depends on factors including the number of participants, the frequency of events, and the analysis method. A confidence interval is not a guarantee about the true value and does not establish that a result is important. Both the interval and the design limitations should inform interpretation.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not the trial's own original design assumptions. For these binary outcomes, the figures are participants per arm, not total events. The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider detecting the stated fraction of the observed effect: 100%, 75%, or 50%. The original trial's sample-size justification and assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm in a hypothetical future study that, under the listed assumptions and effect size, would have an 80% chance of rejecting the no-difference null hypothesis when that effect is real. The 90% power column describes the corresponding planning target for a 90% chance. These are design targets, not assurances about what any particular study will find. Smaller effects require more participants because a smaller contrast is harder to distinguish from random variation under the same assumptions.

The rows based on 100%, 75%, and 50% of the observed effect illustrate how the planned sample size changes when the effect to detect is reduced. They do not establish that the observed effect is the true or expected effect in another study. Planning from a single observed estimate can be uncertain, and the registry record does not report an independently chosen target effect for the original trial.

This is not observed power. Observed power is not a useful substitute for reading the estimate and its confidence interval: the calculations are hypothetical planning illustrations, not a retrospective measure of whether the trial was capable of detecting its result. The displayed calculations use the assumptions stated with the illustrations and should not be treated as the actual design rationale for this pilot.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.115; treatment proportion p₁ = 0.120; average p̄ = 0.118.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4555 = 0.8928.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4555 = 0.3834.
4. n = (0.8928 + 0.3834)² / (0.0044)² = 85,052.9, rounded up to 85,053 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.115384615384615                          # control proportion
p1 <- 0.119760479041916                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1413399)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 85,053 (80% power), 113,862 (90% power)
 75% of observed effect: n per arm = 150,596 (80% power), 201,605 (90% power)
 50% of observed effect: n per arm = 337,468 (80% power), 451,773 (90% power)
power.prop.test: 85052.9 
Simulated power at n = 85,053 per arm: 0.799 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies survival to hospital discharge as the primary outcome and reports one secondary outcome with results. The study objective also names survival to admission and neurologic function at discharge, but numeric results for these outcomes are not reported in the registry record. The record lists no reported analyses. It does not state whether additional outcomes were planned, whether the listed outcomes form a testing hierarchy, or whether results were omitted for any reason.

Multiplicity matters when several outcomes or analyses are considered. General statistical explanation: without an adjustment or a prespecified testing sequence, repeatedly testing hypotheses can increase the chance of at least one result appearing unusual by chance. The secondary p-value should therefore not be interpreted as though it were the only analysis conducted. No multiplicity adjustment is reported in the registry record, and there is not enough information to determine the full family of analyses that may have been planned.

The record does not report how missing outcome data were handled, whether all randomized participants were included in each analysis, or what analysis population was used. The listed group sizes and event counts give the posted summaries, but they do not establish the treatment of participants with unavailable outcome information. No imputation method, sensitivity analysis, or missingness assessment is reported in the registry record. These details matter because missing outcomes can affect both the estimated group contrast and its uncertainty.

The registry's primary outcome description refers to an adjusted odds ratio and confidence interval, but a numeric adjusted result and adjustment variables are not reported in the registry record. The posted comparison measures are unadjusted. The record also does not report the original sample-size justification, planned interim analyses, or a complete statistical analysis plan. Consequently, it is not possible to verify from the registry alone whether the posted analyses follow the original plan or to assess the impact of unreported analytic choices.

15. Safety Results

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

Other (non-serious) adverse events

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

The registry reports zero serious adverse events in the intra-arrest group, among 208 participants at risk, and zero in the post-arrest group, among 334 participants at risk. It also reports zero other adverse events in each group, with the same respective numbers at risk. No serious adverse event terms are listed.

These figures describe the adverse event counts recorded in the registry. They should not be read as proof that no adverse events occurred outside the registry's reporting definitions, observation procedures, or reporting period. The record does not provide additional information about event definitions, ascertainment methods, severity criteria, or completeness of reporting. The death counts in the adverse-event record are not reported.

General statistical explanation: when no events are recorded, the data still leave uncertainty about the underlying event rate, especially when group sizes are limited. A zero count is not evidence that the true risk is exactly zero. These safety summaries also do not provide a direct comparison of all possible harms between strategies. They should be interpreted as registry-reported counts rather than as a comprehensive safety assessment.

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

The posted primary result describes survival to hospital discharge in a randomized comparison of intra-arrest and post-arrest therapeutic hypothermia. The counts are 24 of 208 participants in the intra-arrest group and 40 of 334 in the post-arrest group. The unadjusted risk-difference interval includes zero, and the p-value is 0.878. These data do not provide clear evidence of a difference in the primary outcome, but that is not the same as showing that the strategies are equivalent.

An inconclusive comparison can arise because the estimated contrast is small, because uncertainty is substantial, or both. The posted interval spans values on both sides of no difference. Without a prespecified equivalence or non-inferiority margin, and without a result precise enough to exclude clinically meaningful differences, the record cannot establish equivalence. The registry does not report such a margin or a numeric adjusted estimate for the primary endpoint.

The secondary result concerns prehospital return of spontaneous circulation and has a different pattern in the unadjusted comparison. It does not establish a corresponding difference in survival to discharge. The record does not report numeric results for survival to admission or neurologic function at discharge, despite naming those outcomes in the study objective. The study's outcome set therefore does not support a complete account of the full course from arrest through discharge.

The trial compares two timing strategies and does not include a no-hypothermia group. Its results cannot be used to estimate a contrast against no therapeutic hypothermia. The record also does not provide enough detail to assess all aspects of allocation, missing outcomes, analysis populations, multiplicity, or safety ascertainment. Those limits constrain conclusions from the posted summaries.

General statistical explanation: a p-value is not a measure of clinical importance, and a confidence interval is not a guarantee that the true effect falls within its bounds. Interpretation should consider the endpoint, the estimate's precision, study design, and the analysis context together. The registry results describe this study's posted comparisons; they do not by themselves provide medical advice or settle the broader question of comparative treatment effects.

17. Why This Trial Matters Statistically

This study illustrates why clinical trial results should be read through both endpoint definition and timing. Return of spontaneous circulation is assessed during the prehospital course, while survival to discharge is assessed over the hospital stay. Those outcomes represent distinct stages, and a difference in an early event should not automatically be treated as evidence of a difference in a later one. The registry's objective includes further outcomes, but numeric results for some of them are not reported.

It also demonstrates the distinction between a statistical signal and a precise estimate. The primary unadjusted comparison has a p-value of 0.878 and a confidence interval that includes no difference. The secondary unadjusted comparison has a p-value of 0.018 and an interval that excludes zero. Reading the secondary result without considering multiplicity and its secondary status would overstate what the record can establish.

The posted counts are informative, but raw event totals alone do not make a fair comparison when group sizes differ. Risk differences, risk ratios, and odds ratios express contrasts on different scales, while confidence intervals describe uncertainty around those contrasts. The registry's mention of an adjusted odds ratio also highlights the need to distinguish an adjusted analysis from the unadjusted summaries actually reported numerically.

Finally, the sample-size illustrations show how planning targets depend on the effect assumed for a future study. They are based on the observed effect and stated calculation assumptions; they are not the original design justification and are not observed power. The record's omissions about the original plan, missing data, analysis populations, and multiplicity are themselves statistically relevant. They define what readers can responsibly conclude from the registry without filling gaps by assumption.

18. 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.

This record is limited by the detail available about the trial's design and analyses. The registry lists randomization, a parallel model, and no masking, but does not describe the allocation procedure or who knew group assignment. Arm descriptions do not give additional procedural detail beyond the named strategies and listed intervention. These omissions prevent a fuller assessment of implementation.

The primary endpoint description refers to an adjusted odds ratio and confidence interval, but a numeric adjusted estimate and its covariates are not reported in the registry record. The posted comparison summaries are unadjusted. The original sample-size rationale, analysis population, missing-data handling, interim-analysis plan, and complete statistical analysis plan are also not reported. It is therefore not possible to assess whether the posted summaries include all planned analyses or how alternative analytic decisions might affect the result.

The record names survival to admission and neurologic function at discharge in the study objective, but results for those outcomes are not reported in the registry record. Only one secondary outcome has posted results. The absence of reported results does not establish why they are missing or what their values would be. Likewise, adverse event counts are listed, but the registry does not provide further definitions or ascertainment detail, and death counts in the adverse-event record are not reported.

The pilot study's primary comparison is uncertain, and the secondary result is unadjusted. The registry does not report a multiplicity method or clinical-importance threshold. These limitations do not invalidate the posted summaries; they narrow the conclusions that can be drawn from them and make it important to distinguish recorded results from questions left unanswered by the record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest — NCT01413399.
• Registry record last updated 2022-06-28; status last verified 2021-11.
• Results first posted 2021-12-08.
• 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.

22. Record Summary

The registry record describes a completed randomized, parallel pilot study of intra-arrest versus post-arrest therapeutic hypothermia among participants with non-traumatic out-of-hospital cardiac arrest. It reports enrollment of 542, no masking, and 4 degree chilled saline as the listed intervention. The primary outcome is survival to hospital discharge; the posted counts are 24 of 208 in the intra-arrest group and 40 of 334 in the post-arrest group. The unadjusted primary comparison is inconclusive, with a confidence interval that includes no difference and a p-value of 0.878.

The one secondary outcome with results is prehospital return of spontaneous circulation. Its unadjusted comparison has a p-value of 0.018 and a confidence interval excluding no difference. The registry does not report numeric results for survival to admission or neurologic function at discharge, or a numeric adjusted primary estimate. Details of the original sample-size justification, missing-data handling, analysis populations, and multiplicity procedures are not reported in the registry record.