Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock (NCT03366220), a randomized phase 2 study. The primary outcome is Glycocalyx Breakdown as Assessed by Syndecan-1 Levels.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel-group phase 2 study. Participants were assigned to initial resuscitation with plasma or balanced crystalloids. Random assignment is intended to make treatment groups comparable on average, including for factors that were not measured, but a small trial can still have substantial chance imbalances. The record does not report the allocation ratio, the randomization procedure, or how masking was implemented.

The registry lists an enrollment of 16 participants and a status of terminated. The recorded start date is 2018-03-26, and the primary completion date is 2019-09-17. The sponsor is The University of Texas Health Science Center, Houston. The record does not state why the study was terminated, whether the planned enrollment was reached, or whether recruitment ended early.

The plasma group was assigned an initial dose of 10 mL/kg, with administration at 2-3 mL/kg/hr. The balanced-crystalloid group description refers to Iso-Lyte or Plasma-Lyte and an initial 30 mL/kg within the first 3 hours. Later treatment details are not complete in the registry record. Therefore, the comparison is best understood as a comparison of initial resuscitation strategies, rather than a fully specified comparison of all care throughout the hospital stay.

The primary outcome was syndecan-1 levels, intended to assess glycocalyx breakdown, across five scheduled time points. Secondary outcomes covered fluid volume after the initial bolus, lactate normalization, vasopressor duration, ventilator support, ICU-free days, hospital days, mortality, and acute lung injury. The record lists 22 outcome measures overall, but it does not provide numerical results for these outcomes in the available 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: Patients with a sepsis screening score \> or equal to 4 (which indicates potential sepsis) and with a suspected source of infection were enrolled, and they were later randomized if septic shock developed, per the protocol. Only 8 enrolled patients progressed to septic shock, and therefore only 8 participants were randomized and started the protocol.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data was not collected at end of initial bolus of fluid administration (about 3 hours) and 24 hours for one participant in the initial resuscitation with balanced crystalloids arm.

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 Glycocalyx Breakdown as Assessed by Syndecan-1 Levels, measured over 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and at 24 hours.

The primary endpoint was glycocalyx breakdown assessed by syndecan-1 levels, measured in ng/mL. Measurements were scheduled at 0, 2, the end of the initial fluid bolus at about 3 hours, 12, and 24 hours. The registry describes the outcome as a mean with standard deviation. This means the intended summary was an average level and a measure of the spread of individual values around that average; it does not, by itself, describe the treatment-group contrast or its uncertainty.

As a general measurement principle, using a numerical marker makes a biological process available for repeated measurement and comparison. Measurements at several times can describe how the marker varies during the early period after resuscitation, while a single measurement would not capture that time pattern. The scheduled observations also make clear that the endpoint concerns a trajectory, not simply one final value.

The record notes that one participant in the balanced-crystalloid arm did not have data collected at the end of the initial bolus and at 24 hours. It does not report the actual syndecan-1 values, group means, standard deviations, treatment contrasts, confidence intervals, or p-values. The registry record therefore identifies what was intended to be measured, but does not permit a numerical interpretation of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies this as a randomized, double-masked, parallel-group study. These design labels describe how the comparison was intended to be organized; they do not reveal the statistical tests used to analyze the outcomes. The record does not report the randomization method, allocation ratio, masking procedures, or a detailed analysis plan. It lists zero analyses, so no specific inferential method can be attributed to the posted results.

What does a mean and standard deviation describe?

The primary outcome is described as a mean with standard deviation. In general, a mean is the arithmetic average of a set of measurements. A standard deviation describes how dispersed the measurements are around that average. These are descriptive summaries. They do not show whether two groups differ, how uncertain a difference may be, or whether an observed difference is compatible with chance. For those questions, a treatment contrast and an uncertainty measure, such as a confidence interval, would ordinarily be needed. No such primary-outcome summaries or contrasts are reported in the registry record.

Why do repeated time points matter?

Syndecan-1 measurements were scheduled at 0, 2, the end of the initial fluid bolus at about 3 hours, 12, and 24 hours. In general, measurements from the same participant over time are related rather than independent: a participant’s level at one time may be associated with that participant’s level at another time. An analysis of repeated measurements may account for this within-participant relationship and may assess both group differences and changes over time. This is a general explanation, not a description of the trial’s analysis. The registry record does not report whether a repeated-measures model, separate comparisons at each time, or another approach was used.

There are several possible ways to define a treatment contrast for measurements taken at multiple times. A contrast could focus on a particular time, a change from an earlier measurement, or an overall pattern across scheduled times. Those choices answer different questions and may produce different estimates. The registry record identifies the time points but does not state which contrast was the primary statistical target or how a summary across time was to be formed.

How should uncertainty be read?

In general, a confidence interval gives a range of values that are reasonably compatible with the data under the statistical model used. Its width reflects precision: a wider interval indicates greater uncertainty about the magnitude of the estimated effect. A p-value addresses compatibility with a specified null hypothesis under model assumptions; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value is reported for the primary outcome in this registry record. Without an effect estimate and its uncertainty, the magnitude and precision of the group comparison cannot be assessed.

What does randomization contribute?

In general, randomization supports a fair comparison by assigning treatment independently of measured and unmeasured participant characteristics, on average across repeated assignments. It does not guarantee that small groups will be balanced on every characteristic. The registry lists 16 enrolled participants, but does not report baseline characteristics or group sizes in the available information. Thus the design label alone cannot establish how comparable the observed groups were in this particular trial.

What can planning illustrations tell readers?

Sample-size planning illustrations based on an observed effect are hypothetical calculations, not evidence that a study had adequate power and not estimates of the result’s reliability. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; the target effect is defined as a fraction of the observed effect. For time-to-event outcomes, the stated convention is to give a total number of events; for other outcomes, it is to give participants per arm. These are planning conventions, not observed trial findings. The registry record does not report the original sample-size justification, and the numerical illustration values are not part of the registry entries.

General statistical caution is especially important for small studies: estimates can be imprecise, and chance variation can have a substantial influence on the observed group summaries. This does not determine the direction of any result. Here, because numerical primary-outcome results are not reported, even the observed direction cannot be established from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was scheduled at five time points: 0, 2, the end of the initial bolus at about 3 hours, 12, and 24 hours. The registry record does not identify one time point as the sole primary comparison, explain how the measurements were to be combined, or describe an adjustment for multiple comparisons. The distinction matters in general because testing multiple time points can increase the chance of at least one apparently unusual result when all comparisons are considered together. This is a general statistical issue, not evidence that a particular method was or was not used in the trial.

The record lists 22 outcome measures, including the primary endpoint and secondary outcomes. It does not report how the outcome hierarchy was handled, whether secondary outcomes were considered exploratory, or whether multiplicity adjustments were planned. No analyses are listed in the registry record. Therefore, readers cannot determine which comparisons were actually conducted or how the number of outcomes was reflected in the interpretation.

For the primary outcome, the registry notes that one participant in the balanced-crystalloid group had no data collected at the end of the initial fluid bolus and at 24 hours. It does not explain why these measurements were not collected or how missing observations were addressed. In general, missingness can affect precision and may also affect estimates if the reason data are missing is related to the outcome. The extent and direction of any such effect cannot be evaluated from the record.

The registry record does not state the analysis population, such as whether all randomized participants were intended to be analyzed in their assigned groups. It also does not report participant flow by arm, exclusions, or outcome-specific analysis counts. Without those details, readers cannot assess how closely the analyses followed the randomized allocation or how missing data affected each outcome.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: acute kidney injury (25.0%), liver failure (25.0%), clostridium difficile colitis (25.0%), atrial fibrillation requiring multiple cardioversions (25.0%), acute renal failure requiring intermittent hemodialysis (25.0%).

The registry reports serious adverse events for 4 participants at risk and 4 participants affected in the initial-resuscitation-with-plasma group. It reports the same figures, 4 at risk and 4 affected, in the balanced-crystalloid group. Other adverse events are listed for 0 of 4 at risk in each group. One death is reported in each group. These are the recorded counts and should be read as descriptive safety information, not as evidence that one strategy caused more or fewer events.

The record lists six serious adverse-event terms, each with a percentage of 25.0%: Acute Kidney Injury, Liver failure, Clostridium difficile colitis, atrial fibrillation requiring multiple cardioversions, acute renal failure requiring intermittent hemodialysis, and Enterocutaneous fistula. The registry information does not specify the denominator used for these term-specific percentages or whether events could be counted for the same participant under more than one term. The terms therefore should not be added together or treated as a count of distinct affected participants.

These figures do not give event timing, duration, severity beyond the serious classification, or an adjusted comparison between groups. The enrolled total was 16, but the safety entries list 4 at risk in each arm; the record does not explain the relationship between these numbers. Small descriptive counts cannot establish a causal difference, and the registry does not provide uncertainty estimates for the safety comparison.

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

The registry record documents a randomized phase 2 comparison of initial plasma resuscitation and balanced-crystalloid resuscitation in surgical and trauma patients with septic shock. It identifies syndecan-1 levels as the primary outcome used to assess glycocalyx breakdown and gives the scheduled measurement times. This information clarifies the study question and the kind of measurement intended, but it is not a report of the treatment effect.

No numerical syndecan-1 values or treatment-group comparisons are reported in the registry record. Consequently, the direction, magnitude, and precision of the primary-outcome comparison are unknown from the posted information. The record also does not report numerical results for the listed secondary outcomes. The absence of posted results should not be interpreted as a result showing no difference, nor as proof of a difference.

The safety entries show serious adverse events recorded for 4 participants in each group, other adverse events for 0 of 4 at risk in each group, and 1 death in each group. These are counts, not causal conclusions. They do not establish that the initial fluid strategy caused or prevented any specific event, and the registry does not provide statistical uncertainty for these comparisons. The term-specific serious-event percentages also lack a stated denominator in the available record.

In general, a randomized comparison can help estimate the effect of assigning one strategy rather than another when results, analysis populations, and uncertainty are reported. Randomization alone does not supply those missing results or guarantee precise estimates, particularly in a small study. The listed enrollment is 16, and the study status is terminated, but the reason for termination and the relationship between enrollment and the planned sample size are not reported in the registry record.

The appropriate conclusion is limited: the registry describes a clinical question, a design, and outcome definitions, but it does not provide enough numerical evidence to estimate the primary treatment contrast. The posted information cannot support a claim that either strategy is superior, equivalent, or different on the measured outcomes.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a well-defined study question and an interpretable estimate. The registry identifies a randomized comparison, two initial fluid strategies, and a measurable primary endpoint with scheduled repeated observations. Those elements establish what investigators intended to compare. They do not, by themselves, show the size or direction of an observed difference.

The primary outcome is longitudinal: syndecan-1 levels were scheduled at 0, 2, the end of the initial bolus at about 3 hours, 12, and 24 hours. Such an endpoint raises important analysis questions in general. A reader needs to know whether the focus was a particular time point, a change over time, or a pattern across all measurements, and how measurements from the same participant were handled. The registry record does not report these analysis details or numerical results.

The record also lists 22 outcome measures, spanning laboratory, treatment-duration, hospital-use, and safety outcomes. Multiple outcomes can offer a broad view of a trial, but they make prespecification and transparent reporting especially important. Without the statistical plan and outcome-specific results, readers cannot tell which findings were primary, which were exploratory, or how multiplicity was addressed.

The recorded enrollment of 16 and terminated status make precision and participant accounting particularly relevant, but the registry does not explain termination or provide a complete account of analyzed participants. The serious adverse-event counts are also descriptive and do not substitute for estimates with uncertainty. The central statistical lesson is that design labels and outcome lists are not equivalent to evidence about treatment effects: estimates, uncertainty, analysis populations, and transparent reporting are needed to interpret a clinical comparison.

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 most consequential limitation of the available record is that it contains no numerical primary-outcome results. It gives the outcome definition and time points but not syndecan-1 values, group summaries, treatment contrasts, confidence intervals, or p-values. It also does not provide numerical results for the listed secondary outcomes. The treatment effects therefore cannot be estimated from the registry information.

The registry lists 16 participants enrolled and gives a terminated status, but does not explain why the study was terminated or describe the participant flow by group. The allocation ratio and final group sizes are not reported in the available information. Although the design is identified as randomized and double-masked, the randomization procedure and implementation of masking are not described.

One participant in the balanced-crystalloid group had no primary-outcome data collected at the end of the initial bolus and at 24 hours. The reason for these missing observations and their handling are not reported. The record also does not give an analysis population or counts contributing to each outcome. These omissions prevent assessment of how the missing measurements and any exclusions affected the reported comparisons.

The registry lists 22 outcome measures but no analyses. It does not state which contrasts were prespecified, how repeated measurements were analyzed, or whether multiple comparisons were addressed. The original sample-size justification, any interim analyses, and the detailed statistical analysis plan are not reported in the registry record.

The intervention descriptions are incomplete after the initial dosing information, limiting reconstruction of subsequent treatment. Finally, the safety entries do not specify the denominator for percentages attached to individual serious-event terms, nor whether participants could contribute multiple terms. These limitations restrict interpretation to the design and descriptive counts recorded, rather than conclusions about comparative effectiveness or causation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock — NCT03366220.
• Registry record last updated 2022-04-13; status last verified 2022-04.
• Results first posted 2022-04-13.
• 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

The registry record describes NCT03366220, a phase 2, randomized, double-masked, parallel-group study of initial resuscitation with plasma versus balanced crystalloids in surgical and trauma patients with septic shock. It lists 16 participants enrolled and a terminated status. The recorded start date is 2018-03-26, and the primary completion date is 2019-09-17. The sponsor is The University of Texas Health Science Center, Houston.

The primary outcome was glycocalyx breakdown assessed by syndecan-1 levels in ng/mL, scheduled at 0, 2, the end of the initial bolus at about 3 hours, 12, and 24 hours. One participant in the balanced-crystalloid group had no data collected at the end of the initial bolus and at 24 hours. The registry lists 22 outcome measures and zero analyses. Numerical primary and secondary outcome results are not reported in the registry record.

Serious adverse events were recorded for 4 participants in each group; other adverse events were listed for 0 of 4 at risk in each group, and 1 death was reported in each group. The reason for termination and the trial’s detailed analysis plan are not reported.