This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Guidance of Ultrasound in Intensive Care to Direct Euvolemia (NCT03938038), a randomized na study. The primary outcome is Number of Acute Kidney Injury (AKI)-Free Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03938038 |
| Phase | NA |
| Condition | Acute Kidney Injury |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 415 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The University of Texas Health Science Center, Houston |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns trauma patients at a teaching institution, with acute kidney injury as the condition of interest. The registry describes the intervention’s purpose as guiding fluid resuscitation and assessing acute kidney injury incidence and duration. It does not provide additional eligibility criteria or a more detailed description of the analyzed population.
Intervention
The intervention was serial ultrasound assessments of volume status and fluid responsiveness for goal-directed therapy-based fluid resuscitation. It is described as a diagnostic test. The registry does not report the precise assessment schedule, the ultrasound findings used to guide care, or how clinicians acted on those findings.
Comparator
The comparator was usual care, also listed as a diagnostic test. The registry does not define the specific practices included in usual care, so the comparison is between the named study strategies rather than a fully described fluid-management protocol.
Primary question
The primary endpoint was the number of acute kidney injury-free days within 7 days of injury, summarized using the median and inter-quartile range. The central question was whether the ultrasound-guided strategy was associated with a different distribution of this endpoint than usual care. The registry record does not report the primary result, its uncertainty, or the sponsor’s statistical comparison.
3. Trial Design
GUIDE is recorded as a randomized, cluster-randomized crossover comparative effectiveness trial. The two strategies were serial ultrasound assessments for goal-directed therapy and usual care. The registry lists the sequences as serial ultrasound followed by usual care, and usual care followed by serial ultrasound. It does not provide further details about the clusters, how they were formed, or how randomization was implemented.
In a crossover design, groups or clusters receive strategies in different sequences, allowing comparisons across periods as well as between sequences. This general design can account for some stable differences between clusters, but valid interpretation depends on how period effects, carryover, and clustering are handled. The registry record does not report the period structure, any washout interval, or the statistical model used to address those features. Those details should not be inferred from the design label alone.
The record lists enrollment as 415 and gives study dates from 2019-09-06 to primary completion on 2020-06-27. Its status is completed. Masking is listed as none. The record does not report whether participants, clinicians, outcome assessors, or analysts had any particular role in outcome assessment beyond that masking designation.
The primary endpoint was acute kidney injury-free days within 7 days of injury. Secondary outcomes include acute kidney injury occurrence and stage, renal replacement therapy, fluid amounts and types, and diuretic amounts. The registry lists 16 outcome measures, but does not provide results for the primary endpoint in the registry record for this analysis. The listed secondary outcome names do not establish that their results were reported or analyzed.
The record notes that a simple individual-level re-analysis would be misleading because of the cluster-randomized design, and that only the sponsor’s own analysis is shown. However, no sponsor analysis results or analysis details are reported in the registry record. Thus, the design can be described, but the primary comparison cannot be independently interpreted from the posted result information.
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: Eight different care team clusters will be randomly assigned to either US-guided care or usual care during the 1st half the month and the other technique in the 2nd half. Patient participants will receive either US-guided care or usual care, but not both, and the technique a patient participant receives depends on whether they receive treatment in the 1st or 2nd half of the month. 4 of the 415 enrolled were excluded.
First Half of the Month (15 Days)
| Stage | Serial Ultrasound Assessments for GDT, Then Usual Care | Usual Care, Then Serial Ultrasound Assessments for GDT |
|---|---|---|
| STARTED | 112 | 100 |
| COMPLETED | 112 | 100 |
| NOT COMPLETED | 0 | 0 |
Second Half of the Month (15 Days)
| Stage | Serial Ultrasound Assessments for GDT, Then Usual Care | Usual Care, Then Serial Ultrasound Assessments for GDT |
|---|---|---|
| STARTED | 89 | 110 |
| COMPLETED | 89 | 110 |
| NOT COMPLETED | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Eight different care team clusters will be randomly assigned to either US-guided care or usual care during the 1st half the month and the other technique in the 2nd half. Patient participants will receive either US-guided care or usual care, but not both, and the technique a patient participant receives depends on whether they receive treatment in the 1st or 2nd half of the month. 4 of the 415 enrolled were excluded.
| Characteristic | Unit | Serial Ultrasound Assessments for GDT | Usual Care | Total |
|---|---|---|---|---|
| Participants analysed | 222 | 189 | 411 | |
| Age, Continuous | years | 37 (25 to 60) | 39.5 (27 to 60) | 38 (26 to 60) |
| Sex: Female, Male: Female | Participants | 76 | 54 | 130 |
| Sex: Female, Male: Male | Participants | 146 | 135 | 281 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 44 | 36 | 80 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 151 | 134 | 285 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 27 | 19 | 46 |
| Region of Enrollment: United States | participants | 222 | 189 | 411 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Acute Kidney Injury (AKI)-Free Days, measured over within 7 days of injury.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is the number of acute kidney injury-free days within 7 days of injury. It is intended to capture both whether acute kidney injury occurs and how much of the specified follow-up period is spent free of it. Unlike a simple yes-or-no outcome, a days-based measure can reflect differences in the timing and duration of acute kidney injury, although its exact interpretation depends on the endpoint rules and analysis.
The registry specifies that acute kidney injury will be defined using Kidney Disease Improving Global Outcomes criteria, considering all stages to be acute kidney injury. The listed criteria include serum creatinine at 1.5-1.9 times baseline or an increase of at least 0.3 mg/dL for Stage 1; 2-2.9 times baseline for Stage 2; and 3 times baseline, an increase to at least 4 mg/dL, or initiation of renal replacement therapy for Stage 3.
The endpoint is specified as a median with an inter-quartile range. In general, the median describes the middle of an outcome distribution, while the inter-quartile range describes the spread of the central portion of that distribution. These summaries can be useful when the distribution is not well represented by a mean and standard deviation. The registry record does not report the observed median, inter-quartile range, or a comparison between strategies, so the endpoint’s observed magnitude and precision cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a clinically focused comparison: serial ultrasound assessments for goal-directed fluid therapy versus usual care, with acute kidney injury-free days within 7 days of injury as the primary endpoint. The design is randomized and cluster-randomized crossover. These design features matter to interpretation because observations within the same cluster may be related, and outcomes may also depend on the sequence or period in which a strategy is used. The record states that simple individual-level re-analysis would be misleading.
However, the primary outcome result is not reported in the registry record. The available information does not give a median or inter-quartile range for either strategy, an estimated contrast, a confidence interval, a p-value, or a sponsor-reported hazard ratio. The record also lists zero analyses. Accordingly, the posted information does not establish the direction, magnitude, or precision of the primary comparison. It is not possible to characterize the result as favoring either strategy or as demonstrating a difference or lack of difference.
The registry’s endpoint specification and study design describe what the investigators intended to compare, not what the study found. The acute kidney injury definition includes all stages under the specified criteria. Secondary outcome names cover acute kidney injury occurrence and stage, renal replacement therapy, quantities and types of fluids, and diuretic quantity. Their names alone do not provide observed results. No secondary-outcome estimates or uncertainty measures are reported in the registry record for interpretation.
For a cluster-randomized crossover trial, statistical precision depends on the design and the analysis, including the handling of clustering and period structure. General statistical principle: outcomes from people in the same cluster are often correlated, so treating every observation as statistically independent can overstate the amount of information. The registry’s caution against a simple individual-level re-analysis is consistent with that concern. Since the sponsor’s analysis results and methods are not reported in the registry record, no independent estimate should be substituted.
The record includes serious adverse-event figures by named strategy, as well as percentages for listed serious terms. These are descriptive safety entries, not a randomized causal comparison by themselves. The record does not explain whether categories overlap, how the figures were collected, or whether they were adjusted for the crossover design. They should not be read as proof that either strategy caused an event or changed risk.
Overall, this is a completed trial with a stated primary endpoint and a specified randomized crossover structure, but the reported information does not support a conclusion about the comparative primary outcome. The absence of a reported estimate is distinct from evidence that the strategies had the same outcome. Precision, statistical compatibility with different effects, and practical importance cannot be judged without the sponsor’s outcome estimate and its uncertainty.
9. Statistical Methods Explained
The registry identifies the study as randomized, cluster-randomized, and crossover. Those labels describe different parts of the design. Randomization assigns strategies according to a chance process. Cluster randomization assigns strategies to groups rather than treating each participant as an independently randomized unit. A crossover design uses different strategy sequences across groups or clusters, so the comparison may incorporate observations from more than one period. The registry lists both sequence orders but does not report the cluster count, period duration, or detailed assignment procedure.
Why does clustering matter?
General statistical explanation: people treated within the same cluster may share staff, care routines, or other contextual factors. Their outcomes can therefore be more alike than outcomes from unrelated clusters. An analysis that ignores this dependence can make the effective information appear greater than it is and may produce uncertainty estimates that are too narrow. The registry specifically cautions that a simple individual-level re-analysis would be misleading. The sponsor’s analysis is the appropriate source for the intended design-based comparison, but its estimates and methods are not reported in the registry record.
Why can crossover structure matter?
General statistical explanation: when strategies are used in different periods, the comparison may be affected by changes over time, differences between periods, or effects of an earlier strategy that persist into a later period. A suitable analysis may need to account for the sequence and period structure, depending on how the trial was conducted. The registry does not report the relevant timing details or whether such effects were assessed, so no particular adjustment can be attributed to this trial.
The primary endpoint is a count of acute kidney injury-free days within 7 days of injury, summarized as a median and inter-quartile range. The outcome definition relies on Kidney Disease Improving Global Outcomes criteria and treats all stages as acute kidney injury. General statistical explanation: the median is a rank-based measure of the middle of a distribution, while the inter-quartile range describes the spread of its central observations. These summaries can describe skewed or unevenly distributed data without assuming a symmetric distribution. They do not, on their own, quantify the uncertainty in a comparison between strategies.
What does a confidence interval contribute?
General statistical explanation: a confidence interval gives a range of estimates compatible with the data and the model used, while reflecting sampling uncertainty. Its width helps describe precision; its location describes which effect values are compatible with the analysis. A p-value answers a different question about data compatibility with a specified null hypothesis and model. Neither measure replaces the effect estimate or makes a clinical judgment. The registry record does not report a confidence interval or p-value for the primary endpoint.
The registry entries characterize the analysis approach as time-to-event and state that only sponsor-reported hazard ratios are used. A hazard ratio is a relative comparison of event rates over time under a particular model; its interpretation depends on the event definition, the time scale, and model assumptions. General statistical explanation: a hazard ratio is not the same as a difference in medians, and it does not directly give the absolute probability of an event. No sponsor-reported hazard ratio is included in the registry record information, so none can be interpreted.
Why can over-dispersion matter?
General statistical explanation: over-dispersion occurs when observed variability exceeds what a statistical model expects. For count outcomes, this can happen when observations vary more widely than a simple count model allows. If ignored, estimated uncertainty may be too small. The registry does not report a model for the primary endpoint or indicate whether over-dispersion was assessed; this is a general consideration, not a claim about the trial’s analysis.
The record also describes planning illustrations based on a stated fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event outcomes, those illustrations concern total events; for other outcomes, they concern participants per arm. Such calculations are planning illustrations, not observed trial results or observed power. The registry entries do not give the resulting sample-size estimates, and they do not establish the trial’s original design assumptions or sample-size justification.
Because no primary estimate or sponsor analysis is reported, the key inferential components—effect magnitude, precision, model specification, and design-based uncertainty—cannot be evaluated. General statistical methods can explain what those components mean, but they cannot fill in the missing trial results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and several secondary outcome categories, including acute kidney injury occurrence and stage, renal replacement therapy, fluid quantity and type, and diuretic quantity. It records 16 outcome measures, but the registry entries available do not include a corresponding set of outcome estimates or analysis results. The number of analyses listed is zero.
When a study evaluates multiple outcomes or multiple comparisons, multiplicity can increase the chance of observing an apparently notable result by chance. General statistical explanation: investigators may address this through a prespecified hierarchy, adjustment, or interpretation focused on a primary endpoint. The registry record does not report a multiplicity strategy, so it is not possible to say whether or how the trial addressed this issue. The number of listed outcome measures does not establish how many statistical tests were performed.
The registry record does not report missing-data counts, the amount or pattern of missingness, or the method used to handle missing observations. It also does not report whether outcomes were analyzed according to assignment, exposure, or another analysis population. These details are important because missingness and analysis-population definitions can affect both the estimate and its precision.
The record’s note that only the sponsor’s own analysis is shown, because a simple individual-level re-analysis would be misleading, emphasizes the need for methods that respect the cluster-randomized crossover design. Yet the sponsor’s analytic population, model, missing-data procedures, and multiplicity approach are not reported in the registry record. No further assumptions about them can be made.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Serial Ultrasound Assessments for GDT | 23 | 222 | 10.4% |
| Usual Care | 15 | 189 | 7.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Serial Ultrasound Assessments for GDT | 21 of 222 |
| Usual Care | 15 of 189 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Serial Ultrasound Assessments for GDT | 115 of 222 |
| Usual Care | 119 of 189 |
Most frequent serious adverse event terms
| Event term | Organ system | Serial Ultrasound Assessments for GDT | Usual Care |
|---|---|---|---|
| Death | General disorders | 21 of 222 | 15 of 189 |
| New Onset Congestive Heart Failure | Cardiac disorders | 2 of 222 | 0 of 189 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Serial Ultrasound Assessments for GDT | Usual Care |
|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | 115 of 222 | 119 of 189 |
Serious events with the highest arm-level rate: death (9.5%), new onset congestive heart failure (0.9%).
The registry’s adverse-event entries list the serial ultrasound strategy with 222 at risk, 23 serious adverse events, 115 other adverse events, and 21 deaths. For usual care, the corresponding entries are 189 at risk, 15 serious adverse events, 119 other adverse events, and 15 deaths. The listed serious terms include Death at 9.5% and New Onset Congestive Heart Failure at 0.9%.
These are descriptive entries in the registry record. They do not, by themselves, show that an event was caused by a strategy, nor do they establish a comparative treatment effect. The record does not explain whether serious and other adverse-event categories overlap, the precise event-collection period, or how the figures were analyzed in relation to the cluster-randomized crossover design. The listed deaths should not be assumed to be unrelated to, or caused by, either strategy on the basis of these figures alone.
Interpretation of comparative safety would require clear definitions, denominators appropriate to the analysis, and methods that account for the design, along with uncertainty estimates. Those details are not reported in the registry record. The percentages for the listed serious terms should therefore be read as registry summaries rather than as adjusted comparisons between strategies.
12. What the Result Does, and Does Not, Mean
The record establishes that GUIDE was a completed randomized cluster crossover trial comparing serial ultrasound assessments for goal-directed fluid therapy with usual care in trauma patients. Its primary endpoint was acute kidney injury-free days within 7 days of injury, and acute kidney injury was defined using the stated Kidney Disease Improving Global Outcomes criteria. These details clarify the intended clinical and statistical question.
The record does not report the primary endpoint result, the sponsor’s hazard ratios, or uncertainty estimates for the comparison. As a result, it is not possible to determine from the posted information how the observed outcomes differed, how precisely any difference was estimated, or which effects remain compatible with the analysis. Absence of a reported result is not evidence that the strategies were equivalent, and it is not evidence that either strategy changed the outcome.
The cluster-randomized crossover design also means that an ordinary individual-level comparison would not necessarily provide valid uncertainty. The registry explicitly cautions against such a re-analysis. Without the sponsor’s design-appropriate results and analytic details, recalculating a comparison from group-level entries would not resolve the missing primary outcome information.
The adverse-event entries provide descriptive counts and listed term percentages, but do not establish causation or a comparative safety effect. The secondary outcome names indicate the range of questions the study included; they are not a substitute for reported estimates. Overall, the record describes the trial’s aim, design, endpoint, and selected safety summaries, but does not provide enough outcome analysis to support a conclusion about the comparative primary result.
13. Why This Trial Matters Statistically
This trial illustrates why the unit of randomization matters. In a cluster-randomized design, the assignment process operates at the group level, and outcomes within a group may not be independent. A straightforward comparison that treats all individual observations as unrelated can misstate precision. The registry explicitly recognizes this issue and indicates that only the sponsor’s own analysis should be used rather than a simple individual-level re-analysis.
The crossover feature adds another design consideration. Different clusters follow different strategy sequences, so analysis may need to distinguish sequence and period effects from the strategy comparison. The registry provides the sequence labels but not the detailed timing or model. This makes clear that design labels alone are insufficient for reconstructing a valid estimate.
The primary endpoint also illustrates a distinction between defining an outcome and reporting its result. The record specifies acute kidney injury-free days, the follow-up window, the summary measure, and the diagnostic criteria. Yet the primary estimate and its uncertainty are not reported. A well-defined endpoint helps readers understand what was intended to be measured, but it cannot establish what the comparison found.
Finally, the record separates the existence of a completed trial from the availability of interpretable results. It lists secondary outcomes and descriptive safety entries, but does not provide the sponsor’s primary analysis. For statistical readers, this is a reminder that estimates, uncertainty, and design-appropriate methods are all necessary to judge a comparative result. Without them, the most defensible account is a description of the question and the limits of the reported evidence.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Important details of the cluster structure are not reported in the registry record. The number and definition of clusters, the randomization procedure, and the handling of clustering in the analysis are not specified in the registry record. The record warns that simple individual-level re-analysis would be misleading, but does not provide the sponsor’s model or its results.
The crossover sequence is described, but the timing of periods, any washout interval, and the handling of period or carryover effects are not reported. These omissions limit assessment of how well the statistical analysis matched the design. The descriptions of both intervention sequences are otherwise blank, and the content of usual care is not detailed.
The registry record does not report the primary endpoint values, a comparison estimate, a confidence interval, or a p-value. Nor does it report the sponsor’s hazard ratios. The listed secondary outcomes do not include their results in the registry record. Consequently, the magnitude and precision of the intended comparisons cannot be evaluated.
Further limitations include the absence of reported eligibility details, missing-data information, analysis-population definitions, multiplicity procedures, and the statistical plan. The sample-size information describes planning illustrations based on an observed effect, but does not report their resulting estimates or the trial’s original sample-size justification. It cannot be used to infer observed power or to reconstruct the design rationale.
Safety entries are reported descriptively, without details about event collection, overlap between categories, or design-adjusted comparisons. The record therefore supports description of the listed entries, but not causal safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Guidance of Ultrasound in Intensive Care to Direct Euvolemia — NCT03938038.
- Registry record last updated 2024-04-26; status last verified 2024-03.
- Results first posted 2024-04-26.
- 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.
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18. Record Summary
GUIDE is a completed randomized cluster-randomized crossover trial comparing serial ultrasound assessments for goal-directed fluid therapy with usual care in trauma patients at a teaching institution. The registry lists enrollment as 415, no masking, and study dates from 2019-09-06 to primary completion on 2020-06-27.
The primary endpoint was acute kidney injury-free days within 7 days of injury, summarized by median and inter-quartile range. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes criteria, with all stages considered acute kidney injury. Listed secondary outcomes include acute kidney injury occurrence and stage, renal replacement therapy, fluids, and diuretics.
The primary result and sponsor-reported hazard ratios are not reported in the registry record. The record cautions that simple individual-level re-analysis would be misleading because of the cluster-randomized design. Its safety entries are descriptive and do not establish causation or comparative effects.