Emergency Department (ED) Flow-directed Fluid Optimization Resuscitation Trial (EFFORT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Emergency Department (ED) Flow-directed Fluid Optimization Resuscitation Trial (EFFORT) (NCT01128413), a randomized na study. The primary outcome is Lactate Clearance.

2. Clinical Question

EFFORT was a randomized, parallel-group study without masking. The registry record lists shock as the condition and describes additional objectives involving methods for determining volume responsiveness and the prevalence of volume-responsive shock in the emergency department. It does not report posted results for those additional objectives. The central interpretation is therefore limited to the small subset with a calculable six-hour lactate-clearance endpoint, rather than all enrolled participants.

3. Trial Design

EFFORT was a randomized, parallel-group trial with no masking, sponsored by Washington University School of Medicine. Enrollment was 22. The study began in 2010-07, its primary completion was 2013-11, and its status is listed as terminated. The phase is recorded as NA. The registry record does not report why the study was terminated or provide a fuller account of the circumstances.

The two groups were Fluid Optimization (FO) and Routine Care (RC). In the FO description, passive leg raise testing using Cheetah NICOM was intended to guide intravenous fluid administration. A response meeting the stated threshold was linked to a 500ml normal saline bolus; a response below that threshold was linked to a saline lock. The description is truncated, so further details of the intervention and its implementation are not reported in the registry record. In RC, intravenous fluid administration was left to treating-clinician discretion. The description mentions assessments using Cheetah NICOM, USCOM, inferior vena cava ultrasound collapsibility, and the CURVES Questionnaire, as well as repeat lactate measurements, but is also truncated.

The sole posted primary outcome is median lactate clearance within six hours of the emergency-department stay. Its description notes that only nine participants remained in the emergency department for a full six hours, with five in FO and four in RC. The remaining participants were dispositioned before that time, so a six-hour clearance could not be calculated for them. The record does not report additional posted secondary outcomes or an analysis for the other listed objectives.

Although enrollment was 22, the primary endpoint’s available group counts total only nine. This distinction matters: the reported endpoint summaries do not describe the full enrolled group. The registry record does not report the allocation procedure beyond identifying the study as randomized, the concealment process, or further protocol details.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only 9 total patients (5 Fluid Optimization; 4 Routine Care) stayed in the Emergency Department for a full 6 hours to allow calculation of a 6 hour lactate clearance. The rest of the patients left were dispositioned out of the ED before the 6 hour mark and therefore unable to calculate a 6 hour lactate clearance.

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 Lactate Clearance, measured over The median lactate clearance within 6 hours of the ED stay..

The primary endpoint is lactate clearance, expressed as a percentage, from time zero to within six hours of the emergency-department stay. The registry reports the group median and an interquartile range (IQR). Lactate clearance is a measure of change in lactate over the stated interval; the study summary frames it as a surrogate endpoint for evaluating a fluid-management approach, with the broader aim of assessing potential improvements in morbidity and mortality. It is not itself a direct measure of those clinical outcomes.

A median describes the middle observation in an ordered set, while the IQR describes the span containing the middle half of observations. In general, medians and IQRs can convey the center and spread of data without requiring a symmetric distribution. They do not, by themselves, quantify uncertainty around a difference between groups or establish whether an observed contrast is compatible with chance variation.

The registry reports a median of 54.0 for FO, with an IQR from 19.0 to 57.0, and a median of 56.0 for RC, with an IQR from 49.0 to 59.0. These summaries are based on five and four participants, respectively. The outcome description explains why the endpoint is incomplete: participants dispositioned from the emergency department before the six-hour mark could not contribute a six-hour clearance. The registry record does not report a different endpoint for those participants or a method for accounting for their unavailable six-hour measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the group summaries describe? The endpoint is reported using a median and IQR in each group. In general, the median locates the center of the observed values, and the IQR describes the spread of the middle half. These summaries are often useful when data are skewed or when a few observations might pull an arithmetic mean away from the center. They remain descriptive: without an inferential analysis, they do not quantify the uncertainty in a between-group effect.

For FO, the posted median is 54.0 and the IQR runs from 19.0 to 57.0. For RC, the median is 56.0 and the IQR runs from 49.0 to 59.0. The corresponding endpoint counts are five and four. The record identifies the dispersion measure as an IQR, but it does not post individual participant values or a separate standard deviation. The available summaries therefore do not show the complete shape of either group’s data.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a group difference. Its width depends on the information in the data and on the analysis method. It helps readers distinguish a precise estimate from one that is compatible with a broad range of values. The registry record does not report a confidence interval for the primary endpoint or for a between-group contrast, so the precision of such a contrast cannot be assessed from a posted interval.

What can be concluded without a test?

A formal test evaluates a specified statistical hypothesis using an analysis model and assumptions. A p-value, when reported, describes how unusual the data would be under that hypothesis and model; it is not a measure of clinical importance or the probability that a hypothesis is true. No primary-endpoint test or p-value is posted in the registry record. The reported medians and IQRs should therefore be read as descriptive evidence, not as proof of a statistically detectable difference or of equivalence.

Why does the endpoint count matter?

The primary endpoint was calculable only for participants who stayed in the emergency department for a full six hours. The record gives five participants in FO and four in RC for that calculation, while total enrollment was 22. The endpoint population is consequently narrower than the enrolled population. In general, when outcome availability depends on remaining under observation, the observed subset may not represent everyone enrolled. Whether that issue materially affects these summaries cannot be determined from the registry record because the characteristics and outcomes of participants without six-hour measurements are not reported.

What does randomization contribute?

In general, random assignment is intended to create groups that are comparable on average at the start of a trial, including on factors that may not be measured. It does not guarantee balance in a small trial, and it does not resolve missing outcome data or incomplete reporting. The record identifies EFFORT as randomized but does not report the allocation procedure, concealment method, or a baseline comparison that would allow readers to assess group balance. The posted endpoint counts are especially small, so randomization should not be taken as evidence that the analyzed subset remained comparable.

How should planning illustrations be read?

In general, a sample-size calculation based on an observed effect is a planning illustration, not evidence of the study’s original design or an estimate of observed power. The registry record does not report a sample-size justification or the trial’s statistical plan. It also does not report any inferential analysis for the primary endpoint. Any planning illustration based on the observed summaries should therefore be kept separate from the trial’s actual evidence and should not be interpreted as proof that the study was adequately powered.

The record’s stated assumptions for planning illustrations include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions describe an illustrative calculation rather than a documented protocol plan. The available information does not establish that the trial was designed around those assumptions or that they were used during conduct.

Finally, the endpoint’s status as a surrogate matters for interpretation. In general, a surrogate can be useful for evaluating a biological or intermediate response, but it does not automatically establish effects on outcomes that matter directly to patients. The study summary describes lactate clearance as a surrogate related to morbidity and mortality; the posted primary outcome remains lactate clearance itself. The registry record does not post a direct analysis of morbidity or mortality.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and no posted secondary outcomes. Although the study summary names additional objectives involving methods for determining volume responsiveness and its prevalence in the emergency department, results or analyses for those objectives are not reported in the registry record. The record also lists no analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or a procedure for controlling multiplicity.

In general, testing several outcomes or comparisons can increase the chance of a false-positive finding if each is interpreted independently. A prespecified testing hierarchy or another multiplicity approach can help define how such findings should be interpreted. Since no inferential results or multiplicity plan are posted, there is no basis for assessing how multiplicity was handled. The single posted primary outcome should not be mistaken for evidence that no other analyses were planned or performed; those details are not reported in the registry record.

Missingness is central to the primary endpoint. The registry states that only nine participants, five in FO and four in RC, stayed in the emergency department for a full six hours, and that participants dispositioned before that point could not have six-hour lactate clearance calculated. The record does not report a missing-data method, imputation, sensitivity analysis, or comparison of participants with and without a calculable endpoint.

In general, missing outcome data can affect both the number of observations and the population to which a result applies. The effect depends in part on why measurements are unavailable and how that relates to outcomes. Those relationships are not reported in the registry record, so the direction or size of any resulting bias cannot be determined. The posted endpoint summaries should be understood as summaries of the nine participants with calculable six-hour values, rather than as complete outcome data for all enrolled participants.

The record does not report analysis populations such as intention-to-treat or per-protocol populations. It also does not describe exclusions beyond the explanation that early disposition prevented calculation of the six-hour endpoint. Consequently, the analysis population and handling of participants without the primary measurement are not fully specified.

11. 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 serious adverse events in zero of 11 participants at risk in FO and zero of 11 participants at risk in RC. It also reports other adverse events in zero of 11 at risk in each group. These are counts as recorded in the registry; they do not provide event rates over a stated follow-up period or a detailed account of event collection.

In general, a zero count in a small group means that no events of the specified type were recorded among the listed participants at risk. It does not establish that the true risk is zero, and it cannot rule out uncommon events. The number at risk is important context: these safety counts are based on 11 participants per group, not on a much larger population.

Deaths are not reported in the registry record. No serious adverse-event terms are listed. The record does not provide further details about how events were defined, when safety was assessed, whether events led to discontinuation, or how completeness of reporting was checked. These safety figures should therefore be interpreted as the posted event counts only, without inferring unreported safety outcomes or making a treatment recommendation.

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

The result does show the posted group summaries for six-hour lactate clearance among the participants with a calculable endpoint: a median of 54.0 in FO and 56.0 in RC, with IQRs of 19.0 to 57.0 and 49.0 to 59.0, respectively. The summaries cover five FO participants and four RC participants. They offer a descriptive account of the observed endpoint values in that small subset.

The result does not establish that one approach produces greater lactate clearance than the other. The registry record does not report a statistical test, confidence interval, adjusted estimate, or analysis accounting for the endpoint’s missingness. A comparison of medians alone cannot establish the size or precision of a group effect. Nor does the absence of a reported inferential result mean the groups are equivalent.

The result also does not directly show effects on morbidity or mortality. The study summary characterizes lactate clearance as a surrogate, while the posted primary endpoint is the clearance measure itself. The record does not report a direct analysis of the broader outcomes named in the study summary. Similarly, it does not post findings for the additional objectives concerning volume-responsiveness assessment methods or prevalence.

The endpoint was unavailable for participants who left the emergency department before six hours. Since the record does not describe those participants’ characteristics or outcomes, the nine-person endpoint subset cannot be assumed to represent all 22 enrolled participants. The registry status is terminated, but the reason is not reported in the registry record, and that status does not itself explain either the observed values or the limited endpoint count.

These distinctions are important for a small randomized study. Randomization describes how treatment assignment was structured; it does not make an incomplete endpoint complete, establish precision, or guarantee that the subset with observed outcomes is comparable. The defensible reading is limited to the descriptive summaries and the stated endpoint availability, with broader conclusions left unresolved by the posted results.

13. Why This Trial Matters Statistically

EFFORT highlights a common statistical distinction between enrollment and endpoint availability. The trial enrolled 22 participants, but the primary endpoint required a full six-hour stay in the emergency department and was calculable for only nine. The reported medians therefore describe a selected measurement subset, not the entire enrolled group. Keeping those denominators visible is essential when interpreting any group summary.

The trial also illustrates why a surrogate endpoint and a clinical outcome are not interchangeable. Lactate clearance was selected as a short-term measure related to the study’s broader interest in morbidity and mortality. The registry, however, posts the lactate-clearance summaries and no direct morbidity or mortality analysis. A measured biological response can be informative, but it cannot on its own settle questions about outcomes that were not reported.

Small groups make uncertainty particularly important. Medians and IQRs convey the observed center and spread, while a confidence interval or prespecified inferential analysis would address uncertainty in a comparison. Neither is posted for the primary outcome. The result consequently demonstrates how descriptive statistics can be reported without enough accompanying analysis to support a precise comparative interpretation.

Finally, the registry lists additional objectives but no posted secondary outcomes or analyses. That gap makes it important to distinguish stated research aims from results available for evaluation. The record provides a useful case for reading outcome definitions, time windows, analysis populations, and missing measurements together rather than treating a headline summary as a complete account of the trial.

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.

The primary endpoint is based on only nine participants: five in FO and four in RC. Although the registry reports enrollment of 22, it explains that participants dispositioned from the emergency department before a full six-hour stay could not have the endpoint calculated. This limits the amount of observed outcome information and narrows the population represented by the posted summaries.

The registry record does not report why participants left before six hours, whether the timing of disposition differed between groups, or how participants with and without endpoint measurements compared. It also does not report an approach to missing data or sensitivity analyses. As a result, the potential influence of incomplete endpoint availability cannot be assessed from the posted record.

The primary outcome is a surrogate, and no direct morbidity or mortality results are posted. No secondary outcomes or analyses are posted despite the additional objectives described in the study summary. The registry also does not report a statistical analysis plan, inferential comparison, confidence interval, allocation procedure, or sample-size justification. These omissions constrain interpretation of both the study’s planned methods and the precision of its findings.

Descriptions of both intervention groups are truncated. The available record identifies key procedures and clinician discretion but does not give the complete protocols. The reason for the terminated status is not reported in the registry record. Safety information is limited to the recorded adverse-event counts; deaths are not reported, and the record does not provide further collection or follow-up details. These limitations do not negate the posted descriptive values, but they restrict the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Emergency Department (ED) Flow-directed Fluid Optimization Resuscitation Trial (EFFORT) — NCT01128413.
• Registry record last updated 2016-04-01; status last verified 2016-03.
• Results first posted 2016-03-07.
• 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.

18. Record Summary

EFFORT (NCT01128413) was a randomized, parallel-group study without masking, sponsored by Washington University School of Medicine. It enrolled 22 participants with shock and is listed as terminated. The study began in 2010-07, with primary completion in 2013-11.

The posted primary endpoint was median lactate clearance within six hours. It was calculable for nine participants who remained in the emergency department for a full six hours: five in Fluid Optimization and four in Routine Care. The reported medians were 54.0 and 56.0, respectively; the corresponding IQRs were 19.0 to 57.0 and 49.0 to 59.0.

The registry record lists no posted secondary outcomes or analyses. It does not report an inferential comparison for the primary endpoint, a statistical analysis plan, or a reason for termination. Serious and other adverse events were recorded in zero of 11 participants at risk in each group; deaths are not reported in the registry record.