Isotonic Solution Administration Logistical Testing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Isotonic Solution Administration Logistical Testing (NCT02345486), a randomized na study. The primary outcome is Proportion of Isotonic Crystalloid Which is 0.9% Saline.

2. Clinical Question

3. Trial Design

The registry describes a completed, randomized, parallel-group pilot study with no masking. Enrollment was 974. The listed phase is NA. The study was sponsored by Vanderbilt University. Its recorded start was 2015-02 and its primary completion was 2015-06.

The study was designed as preparation for a larger trial comparing 0.9% sodium chloride with physiologically balanced isotonic crystalloids in intensive care patients. The registry’s summary says the pilot would enroll patients admitted to the medical intensive care unit at a single tertiary center over a six-month period. It describes the larger planned trial as cluster-randomized and multiple-crossover; that description concerns the planned larger trial, while the pilot record lists randomized allocation and a parallel model. The allocation unit for the pilot is not reported in the registry record.

The two arms were defined by the fluid to be administered when an isotonic crystalloid was ordered. One arm was assigned 0.9% sodium chloride; the other was assigned Lactated Ringers or Plasmalyte-A. Masking was none. The record does not report the practical procedures used to implement assignment, how contraindications were handled, or whether adherence to assignment was assessed beyond the primary outcome.

Alongside the primary logistical objective, the pilot aimed to demonstrate feasibility of automated electronic collection of demographic characteristics, illness severity, fluid management, vital signs, laboratory data, acute kidney injury and renal replacement therapy, and outcomes. The registry lists secondary fluid and laboratory measures, but does not report their numerical results in the information available for this analysis.

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 Proportion of Isotonic Crystalloid Which is 0.9% Saline, measured over 30 days.

The primary endpoint was each participant’s proportion of total intravenous isotonic crystalloid administered in the intensive care unit that was 0.9% sodium chloride, censored at 30 days. It was calculated as the volume of saline divided by the volume of saline plus the volume of balanced crystalloid received. The registry describes a range from 0.0, meaning no saline received, to 1.0, meaning only saline received. The recorded unit is percentage of fluid that was saline.

This measure is directly connected to the pilot’s operational purpose. If assigned fluid is consistently used when an isotonic crystalloid is ordered, the proportion of fluid that is saline should reflect the difference in assigned fluids between groups. The registry also states that the electronic order-entry tool was intended either to ensure administration of assigned study fluid or to record contraindications. The endpoint therefore assesses fluid exposure and implementation, not by itself whether one fluid changes a patient’s health outcome.

A participant’s value can depend on the mix and volume of isotonic crystalloid received during the admission. The definition does not incorporate non-isotonic intravenous fluids into its numerator or denominator. The registry does not report additional endpoint-handling details, such as how participants with no isotonic crystalloid exposure were treated in the analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported analysis uses the Wilcoxon (Mann-Whitney) method to compare the primary outcome between groups. This is a rank-based approach: rather than relying directly on a model for normally distributed measurements, it orders observed values and assesses how those values are distributed between groups. It can be useful when outcome distributions are skewed or contain many tied values. The registry record does not report whether the endpoint distribution was skewed, how ties were handled, or what specific implementation of the test was used.

What does the reported mean difference describe?

The listed parameter is mean difference in final values. It describes a contrast between groups on the recorded endpoint scale, which is the proportion of isotonic crystalloid that was saline. The reported estimate is 0.70, with a 95% confidence interval from 0.66 to 0.74. The group codes are not mapped to named arms in the analysis listing, and the order of subtraction is not reported. Accordingly, the numerical estimate does not identify which named arm had the higher outcome.

A rank-based test and a mean-difference estimate answer related but not identical questions. A rank test uses the ordering of observations, while a mean difference concerns the difference between group averages. A mean difference may be reported alongside a rank-based test, but interpretation depends on how the estimate and uncertainty interval were constructed. The registry does not give those construction details. It is not possible to infer from the method label alone that the test was a test of means, or to reconstruct an alternative analysis.

How should the confidence interval be read?

A confidence interval communicates uncertainty around an estimated contrast. Under the method’s assumptions, intervals formed in this way would cover the underlying contrast at the stated long-run rate. The reported interval runs from 0.66 to 0.74 at the 95% level. It characterizes statistical uncertainty in the reported comparison; it does not account automatically for every source of uncertainty, such as missing observations, implementation deviations, or limitations in how participants were selected.

The p value, 0.001, is the reported measure of compatibility between the observed data and a specified null comparison under the analysis procedure. It is not the probability that the null hypothesis is true, nor does it express the probability of a clinical outcome. The registry does not describe whether this was a prespecified test, whether any covariates were included, or whether the reported p value was adjusted for multiple testing.

Why can over-dispersion matter?

As a general statistical point, over-dispersion occurs when observations vary more than a model assumes. In a cluster-randomized study, participants within the same cluster may have more similar outcomes than participants in different clusters. Treating all participants as independent can then understate uncertainty. The study summary describes a future larger trial as cluster-randomized; the pilot record itself lists randomized allocation and a parallel model, and its allocation unit is not reported in the registry record. The analysis context flags a cluster-randomized design as a reason that a simple individual-level recalculation would be misleading. The reported sponsor analysis is therefore the appropriate result to discuss rather than an unadjusted reconstruction from individual-level summary values.

What do the planning illustrations represent?

Any sample-size illustrations associated with the results are planning scenarios, not observed power and not evidence about how many participants would have been needed under the original protocol. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider effects expressed as fractions of the observed effect. For time-to-event outcomes, the illustrations refer to total event counts; for other outcomes, they refer to participants per arm. These assumptions describe the illustration method, not the original trial’s design or sample-size justification. The registry record does not report the pilot’s sample-size justification.

General statistical caution applies to all such planning calculations: their estimates depend on the effect size and design assumptions chosen. They cannot establish that a future study will reproduce the pilot’s effect, and they do not convert a pilot result into evidence of observed power. The record does not report an interim-analysis plan, a detailed statistical analysis plan, or other information needed to assess how these procedures were specified before the data were examined.

10. Analyses Reported by the Sponsor

The numerical result discussed is the sponsor’s reported analysis: a mean difference in final values of 0.70, a 95% confidence interval from 0.66 to 0.74, and p = 0.001. No simple unadjusted recalculation is presented. The analysis context flags a cluster-randomized design as a reason an individual-level recalculation could be misleading, because such a calculation may fail to account for dependence among participants within clusters. In that setting, the sponsor’s own analysis takes precedence.

The record lists randomized allocation and a parallel model for the pilot, while its study summary describes a planned larger study as cluster-randomized and multiple-crossover. The allocation unit for the pilot and the analysis details needed to reconcile those descriptions are not reported in the registry record. The reported method is Wilcoxon (Mann-Whitney), while the parameter is mean difference; the estimator and interval construction are not specified. The available details therefore support reporting the sponsor’s result as posted, but not reconstructing its calculation or assigning the positive contrast to a named arm. The group-code mapping and contrast direction are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures and one reported analysis. The primary measure concerns the proportion of isotonic crystalloid that was saline. Listed secondary measures include the proportion of isotonic crystalloid that was physiologically balanced; total intravenous input; total isotonic crystalloid input; total intravenous colloid input; total intravenous blood product administration; highest serum chloride and sodium between enrollment and Day 30; and lowest bicarbonate concentration between enrollment and Day 30.

Having several outcomes can create multiplicity: when many statistical tests are performed, the chance of at least one apparently unusual result can increase. Whether and how to address that issue depends on which outcomes and comparisons were prespecified and on the intended claims. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a detailed statistical analysis plan. The single analysis listed should not be taken to establish that no other analyses were performed; additional analysis details are not reported in the registry record.

The registry description defines a 30-day censoring horizon for the primary outcome, but does not report how missing endpoint values were handled, whether participants with no qualifying crystalloid exposure were included, or how incomplete follow-up affected the analysis. It also does not report the analysis population, exclusions from analysis, or whether participants were analyzed according to randomized assignment. These omissions limit assessment of possible bias from missing data or departures from assignment.

The pilot aimed to collect several types of clinical and laboratory information electronically. That objective does not establish that every listed measure was complete or available for every participant. Numerical results for the listed secondary measures are not reported in the registry record discussed in the primary comparison. Conclusions should therefore remain tied to the outcome and analysis that are actually reported.

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.

The adverse-event record lists 0 serious adverse events among 454 participants at risk in the 0.9% sodium chloride group and 0 among 520 participants at risk in the physiologically balanced fluid group. It also records 68 deaths in the saline group and 72 in the balanced-fluid group. These are raw counts, not adjusted comparisons. The registry does not provide a statistical comparison of deaths in the information, and no difference or rate should be inferred from the counts alone.

The adverse-event listing gives no serious adverse-event terms. It does not report definitions, surveillance procedures, attribution to study fluid, or the relevant follow-up window for these counts. The at-risk counts are the denominators recorded for the adverse-event listing; the record does not explain their relationship to the full enrollment or provide additional analysis-population details. Zero reported serious adverse events does not establish that no adverse events of any kind occurred, nor does it establish equivalence between groups. Death counts likewise do not identify causes or establish a treatment effect.

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

The result concerns the composition of isotonic crystalloid administered during intensive care, measured as the proportion that was saline and censored at 30 days. The registry reports a difference between groups of 0.70, with a 95% confidence interval from 0.66 to 0.74 and p = 0.001. It does not identify the direction of the contrast by named arm in the analysis details, so the numerical result cannot be assigned to saline versus balanced fluid from the reported comparison alone.

The outcome fits the pilot’s operational aim: examining whether an electronic ordering tool could support use of assigned fluid or document contraindications. It is not, by itself, a result about acute kidney injury, kidney replacement therapy, mortality, or another clinical benefit or harm. Although acute kidney injury is listed as a condition and the summary describes plans to collect kidney-related outcomes, the primary comparison is fluid exposure. Results for those clinical outcomes are not reported in the registry record summarized in this analysis.

The study was a pilot at a single tertiary center, intended to inform a larger trial. Its findings therefore describe the recorded comparison in that study context; they do not establish how the procedure would perform elsewhere or in a later trial. The registry does not report enough detail to determine the allocation unit, analytic population, missing-data handling, or the exact construction of the reported interval. Those limitations affect how fully the estimate can be evaluated.

The confidence interval and p value indicate statistical uncertainty and evidence under the reported analysis, not certainty about a clinical interpretation. The analysis method is named as Wilcoxon (Mann-Whitney), while the estimate is labeled a mean difference, and the registry does not supply the details that connect these. The appropriate conclusion is limited: a sponsor-reported comparison of the primary fluid-proportion outcome is available, but its direction and implications for patient outcomes are not established by the reported information.

14. Why This Trial Matters Statistically

This pilot is statistically informative because its main question is about whether a randomized fluid assignment can be implemented and measured in routine intensive care. Such a question differs from asking whether an intervention improves a clinical endpoint. A measure of the fluid actually administered can help assess whether the study procedures create distinct exposure between groups, which is a prerequisite for interpreting a later clinical comparison.

The design context also highlights why analysis must follow the randomization structure. The registry summary describes a larger planned study as cluster-randomized and multiple-crossover, while the pilot record lists randomized allocation and a parallel model. The allocation unit for the pilot is not reported in the registry record. Where participants are grouped within randomized units, their outcomes may be correlated; as a general statistical principle, an analysis that assumes full independence can give misleading uncertainty. The analysis context consequently cautions against a simple individual-level re-calculation.

The reported endpoint is a continuous proportion tied to actual fluid exposure, and the analysis listing combines a rank-based method with a mean-difference parameter. That pairing makes transparent reporting of the estimand, contrast direction, and uncertainty construction especially useful. In this record, the group codes are not linked to named arms in the analysis result, and those methodological details are not reported. These gaps show why numerical estimates should be interpreted together with design and analysis descriptions.

Finally, a pilot can address feasibility and data collection without resolving clinical effectiveness. The registry’s stated logistical aims and the narrow primary endpoint provide context for what the reported comparison can answer. Separating implementation evidence from patient-outcome evidence helps prevent a statistically clear result on one measure from being read as a conclusion about another.

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 comparison’s direction is not identifiable from the analysis listing because the reported groups are coded and the subtraction order is not stated. This prevents attributing the positive mean difference to either named fluid arm. The analysis labels a Wilcoxon (Mann-Whitney) method but reports a mean difference; the estimator and confidence-interval construction are not described in the registry record.

The study is described as a single-center pilot intended to prepare for a larger trial. Its primary outcome measures fluid composition, not a clinical outcome. The record does not provide numerical results for acute kidney injury, renal replacement therapy, or other clinical endpoints in the primary comparison. The allocation unit for the pilot is also not reported, while the summary’s cluster-randomized description refers to the planned larger study. This leaves uncertainty about the design structure relevant to assessing analysis methods.

Important operational and analysis details are not reported in the registry record: how assignment was implemented, whether contraindications were recorded, how adherence was assessed, how participants with no isotonic crystalloid exposure were handled, how missing data were treated, and which analysis population was used. The protocol’s sample-size justification, interim analyses, and detailed statistical plan are not reported in the registry record. The listed adverse-event counts lack event definitions, causes of death, and a specified follow-up window.

These limitations do not negate the posted estimate, but they constrain its interpretation. In particular, the estimate should not be treated as a direct comparison of patient benefit or harm, and the available information does not support reconstructing the sponsor’s analysis independently.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Isotonic Solution Administration Logistical Testing — NCT02345486.
• Registry record last updated 2019-11-13; status last verified 2019-10.
• Results first posted 2019-10-25.
• 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

NCT02345486, titled Isotonic Solution Administration Logistical Testing, is recorded as a completed randomized, parallel-group pilot with no masking. Enrollment was 974, and the listed condition is acute kidney injury. The study compared assignment to 0.9% sodium chloride with assignment to physiologically balanced fluid, Lactated Ringers or Plasmalyte-A. Its primary outcome was the proportion of intensive care isotonic crystalloid that was saline, censored at 30 days.

The registry reports a mean difference in final values of 0.70, with a 95% confidence interval from 0.66 to 0.74 and p = 0.001, using a Wilcoxon (Mann-Whitney) method. The contrast direction is not identified by named arm. The study’s stated emphasis was testing order-entry logistics and automated data collection in preparation for a larger trial. Interpretation is limited by unreported analysis details, including the allocation unit, missing-data procedures, and analysis population.