Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS (NCT02276066), a non-randomized na study. The primary outcome is Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline.

2. Clinical Question

The clinical rationale in the registry record describes a proposed pathway linking persistent inflammation, kidney changes, declining kidney function, and PICS. It also notes that features of chronic critical illness may resemble protein-energy malnutrition and muscle wasting associated with chronic kidney disease. These statements describe the investigators’ rationale and hypothesis; they are not findings established by the listed endpoint.

GFR assessment was timed differently according to hospitalization status. For the inhospital group, the baseline assessment was at inpatient day 14. For participants discharged before day 14, baseline was the discharge date. Follow-up GFR assessment was planned at 1 year for both groups. The endpoint therefore centers on comparing two ways of characterizing kidney function at baseline, not on a randomized test of a treatment or an isolated estimate of whether an intervention changes survival.

3. Trial Design

The registry record describes NCT02276066 as a completed, non-randomized, single-group study with enrollment of 73 and no masking. The listed phase is NA. The study began in 2015-02 and its primary completion date is 2023-05-20. University of Florida is listed as the sponsor. These design details identify the structure and status of the study, but do not establish the strength or direction of any clinical association.

Although the record labels the model single-group, it also describes two groups based on whether participants remained hospitalized at day 14 or had been discharged earlier. The first group had GFR assessment at inpatient day 14 and again at 1 year follow-up. The second had assessment at discharge before day 14 and again at 1 year follow-up. These are status-defined groups, not groups assigned to different treatments. The registry explicitly notes that the allocation is non-randomized and that the groups are not a like-for-like control comparison.

The listed assessments include GFR by Iohexol, urine collection, and blood samples. Secondary outcomes include estimated GFR by serum creatinine and calculated GFR using urea concentration and creatinine clearance. The primary endpoint concerns the difference between measured Iohexol GFR and calculated GFR from creatinine at baseline. The record states that Iohexol was contraindicated for many patients, which is relevant to who could contribute to the primary comparison.

The record lists 6 outcome measures and 1 analysis. That count does not describe the full analytic approach or resolve which participants contributed to each measure. Details about eligibility criteria, recruitment methods, follow-up completeness, prespecified statistical models, covariate adjustment, and sample-size justification are not reported in the registry record. It is therefore not possible to determine from the record how the study planned to address confounding, missing observations, or uncertainty in the primary endpoint estimate.

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: GFR by iohexol and eGFR by CKD epi at baseline. The iohexol could not be performed on many patients because it was contraindicated

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 Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline, measured over For Arm 1 baseline is measured GFR at 14 days inhospital with sepsis or sepsis diagnosis. For Arm 2 baseline is measured GFR at discharge date prior to day 14 of hospitalizaton with sepsis or sepsis diagnosis..

The primary endpoint is the difference between measured GFR by Iohexol and calculated GFR from creatinine at baseline, expressed in ml/min/1.73m2. It is described as a mean with standard deviation. The baseline timing depends on hospitalization status: inpatient day 14 for participants still hospitalized, or discharge before day 14 for participants discharged earlier. The population description specifies measured GFR by Iohexol and estimated GFR by CKD epi at baseline.

Comparing a measured kidney-function assessment with a calculated estimate can describe how closely the two approaches align in the study population. A difference can also reveal systematic disagreement between methods, although the registry record does not specify the subtraction order. The endpoint is a measurement comparison; it is not itself a clinical outcome such as survival, progression of chronic kidney disease, or PICS.

The stated reason for using this comparison is to examine kidney function in the context of the study’s hypothesis about sepsis, chronic critical illness, and PICS. However, the primary endpoint definition alone cannot establish that kidney dysfunction causes PICS or changes survival. It also cannot establish whether either GFR method is more accurate without an appropriate reference and supporting analysis.

The registry record notes that Iohexol could not be performed on many patients because it was contraindicated. This limits the available paired measurements and may affect how representative the endpoint population is of all enrolled participants. A numerical endpoint estimate, its standard deviation, and a confidence interval are not reported in the registry record, so the magnitude and precision of any observed difference cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measurement: the difference between measured GFR by Iohexol and calculated GFR from creatinine. The registry identifies the summary parameter as a mean and the dispersion measure as a standard deviation. A mean describes the average value in the analysis population. A standard deviation describes how spread out individual values are around that mean. Neither summary is reported numerically for the primary endpoint in the registry record.

What does a mean difference describe?

A paired measurement comparison asks how two methods differ when both are assessed for the same participant. The average difference can indicate whether one method tends to yield values higher or lower than the other, but the direction depends on the subtraction order. The registry record describes the difference but does not state that order. The mean alone also does not show whether individual differences are tightly clustered or widely spread; that is why a measure of dispersion is useful.

In general, a confidence interval describes a range of values compatible with the data and the statistical model, and indicates uncertainty around an estimate. It is not reported for this primary outcome in the registry record. Without the estimate and its uncertainty, readers cannot assess how precisely the average method difference was determined. A significance test, if one had been reported, would address compatibility with a specified null hypothesis; it would not by itself establish clinical importance or agreement for individual participants.

Why compare measured and calculated GFR?

Calculated estimates and direct measurement approaches do not necessarily give identical values. Comparing them can help characterize their relationship in the observed population. In general, the variability of paired differences matters because a small average difference could coexist with substantial variation among individuals. Conversely, a nonzero average difference does not alone show whether the difference is consequential for a particular clinical decision. The registry record does not report a clinical threshold for interpreting this endpoint.

The record identifies the calculated comparison as based on creatinine and the population description refers to estimated GFR by CKD epi. It also lists secondary outcomes involving estimated GFR by serum creatinine and calculated GFR using urea concentration and creatinine clearance. The number of outcome measures is 6. The record does not give numerical results for these secondary measures, or describe how their results relate to the primary comparison.

What do the two groups represent?

The groups are defined by whether participants remained in hospital at day 14 or left before day 14. Their baseline assessments occur at different times: inpatient day 14 in the first group and discharge in the second. This timing may be clinically practical, but it means that baseline is not a single shared calendar time after sepsis diagnosis for every participant. Since group membership is not randomized, observed group differences cannot be interpreted as effects of a treatment assignment. General statistical reasoning also cautions that hospitalization status may be associated with other characteristics that influence kidney measurements. A method for accounting for those factors is not reported in the registry record.

How should missingness be considered?

The registry record states that Iohexol could not be performed on many patients because it was contraindicated. This means the primary comparison could be based on a subset able to undergo the measurement. In general, missing or unavailable measurements can affect both the precision and representativeness of an estimate, particularly if their availability is related to participants’ health or measured kidney function. The record does not quantify how many measurements were unavailable, explain the handling of unavailable assessments, or report whether the analysis population differed from the full enrolled population.

The follow-up plan includes GFR assessment at 1 year, but the record does not give follow-up completion or explain the handling of missing follow-up values. It also does not report a model for repeated measurements. As a result, no particular method for longitudinal data, imputation, or complete-case analysis should be assumed.

What can the design support?

In general, an observational study can describe measurements and associations in the enrolled population. Without random allocation, comparisons between groups may be influenced by factors related to group membership. A single-group model and status-defined subgroups do not create a randomized control comparison. The registry record does not report covariate adjustment, a causal analysis, or a prespecified statistical plan for the primary outcome. It also does not report a sample-size justification or interim analyses.

The record lists 1 analysis, but that count does not specify the statistical test, model, confidence level, or treatment of multiple outcomes. No inferential method for the primary endpoint is described. The registry’s sample-size assumptions are described as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is not the study’s own design justification, and its sample sizes are planning illustrations rather than observed power. It should not be read as proof that the study had a particular probability of detecting an effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 1 analysis. It does not report a multiplicity strategy, such as whether one endpoint was designated for formal inference while other outcomes were descriptive, or whether statistical testing across outcomes was adjusted. When several outcomes are examined, general statistical reasoning recognizes that the chance of at least one apparently unusual result can change depending on the testing plan. No claim about the study’s actual error control can be made without the plan and results.

The primary endpoint is identified, but a complete statistical analysis plan is not reported in the registry record. Details about model specification, covariate adjustment, confidence intervals, hypothesis tests, subgroup analyses, and handling of repeated measurements are not reported. Interim analyses are also not reported in the registry record. The record does not provide a sample-size justification tied to the study’s own planned primary analysis.

The inability to perform Iohexol in many patients because it was contraindicated raises a specific missing-measurement concern for the primary comparison. The number of unavailable tests, reasons beyond the stated contraindication, and method for handling missing values are not reported. The number contributing paired measurements is not reported either. Follow-up at 1 year is described, but completeness and the treatment of missing follow-up measurements are not reported.

The analysis populations are not reported in the registry record. It is therefore unclear which enrolled participants contributed to each endpoint, whether all available observations were included, and how exclusions or incomplete assessments were handled. These omissions matter because the enrollment count alone does not show the effective sample size for an endpoint requiring both measured and calculated GFR values.

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: readmission for wound care (14.6%), death (14.6%), abdominal pain (12.2%), kidney stones (6.2%), abdominal abscess (6.2%).

The registry reports serious adverse event figures separately for the inhospital group at day 14 and the group discharged before day 14. In the inhospital group, 24 of 41 participants are listed as affected by serious adverse events; in the discharged group, 15 of 32 are listed as affected. Other adverse events are listed as affecting 0 participants in each group. The record also reports 6 deaths in the inhospital group and 1 in the discharged group.

The listed serious-event terms and percentages are readmission for wound care, 14.6%; death, 14.6%; abdominal pain, 12.2%; kidney stones, 6.2%; abdominal abscess, 6.2%; and blood transfusion, 3.1%. The registry record does not state the denominator or clarify whether participants could contribute to more than one listed term. These percentages should therefore be read as posted, without deriving additional rates or assuming that the terms are mutually exclusive.

These counts are descriptive registry reports, not a randomized safety comparison. The groups differ by hospitalization status, and the record does not establish that events were caused by the diagnostic assessments. It does not report event timing, severity details beyond the serious-event classification, attribution, or overlap between the death count and serious-event counts. The figures do not by themselves determine whether an assessment was safe or unsafe.

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

The study addresses an important measurement and disease-process question: whether kidney function in sepsis and chronic critical illness relates to the proposed development of PICS. Its primary endpoint is narrower than that overall hypothesis. It compares measured GFR by Iohexol with calculated GFR from creatinine at baseline. The endpoint could characterize agreement or average difference between methods among participants with the required measurements, but it does not directly measure PICS, chronic kidney disease progression, or survival.

The registry record does not report a numerical primary endpoint result. Without a mean difference, standard deviation, confidence interval, or other inferential result, the magnitude and precision of the comparison are unknown from this record. No direction of difference can be stated. The study’s hypothesis and rationale should not be mistaken for results.

The group structure also limits interpretation. Participants were grouped according to whether they remained hospitalized at day 14 or were discharged earlier, not randomly assigned. This distinction is important: differences between such groups may reflect their clinical circumstances or other characteristics, and cannot be attributed to the group label itself. The record explicitly cautions that the groups are not a like-for-like control comparison.

The record notes that Iohexol was contraindicated for many patients. Since the primary endpoint requires measured GFR by Iohexol, missing or unavailable measurements may limit the number of participants represented in the comparison. The record does not report the endpoint analysis population or missing-data handling, so the extent of this limitation cannot be quantified.

Accordingly, the posted information supports describing the study design, assessment schedule, hypothesis, and reported safety counts. It does not establish that kidney dysfunction causes PICS or decreased survival, nor does it show that one GFR approach is more accurate. Those conclusions would require relevant results and analyses that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable because it places a measurement question within a broader observational investigation of sepsis and chronic critical illness. Measured and calculated GFR are distinct approaches to characterizing kidney function. Their comparison is meaningful only when the endpoint definition, paired observations, and uncertainty are understood. The record identifies the comparison and its units, but does not report its numerical result, leaving the central quantitative finding unavailable.

The study also illustrates why the analysis population matters. Iohexol was contraindicated for many patients, while the primary outcome depends on Iohexol measurement. The enrolled population of 73 therefore cannot automatically be treated as the number contributing to the primary endpoint. The record does not report how many participants had usable paired measurements or how unavailable tests were handled.

Its hospitalization-based groups underscore the distinction between describing subgroups and making a controlled comparison. Remaining hospitalized at day 14 versus discharge before day 14 defines groups with different assessment timing and potentially different clinical circumstances. With non-randomized allocation, group comparisons cannot be treated as if participants had been assigned to a common intervention and control condition.

Finally, the proposed pathway from kidney dysfunction to PICS and survival is broader than the primary measurement endpoint. Keeping those levels of inference separate is important: a method-comparison result could inform measurement, but it would not alone establish a causal mechanism or clinical outcome effect. The registry record’s incomplete outcome and analysis details make that distinction especially important when interpreting the study.

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 direct limitation is that a numerical primary endpoint result is not reported in the registry record. The mean difference, its standard deviation, and its precision are unavailable, so the main measurement comparison cannot be quantitatively interpreted from the record.

The record states that Iohexol could not be performed on many patients because it was contraindicated. It does not quantify the number of unavailable measurements or describe how these cases were handled. As a result, the number contributing to the primary endpoint and the representativeness of that analysis population are unknown.

The groups are defined by hospitalization status, and baseline timing differs between them. The inhospital group is assessed at inpatient day 14; the group discharged earlier is assessed at discharge. Since the study is non-randomized, group differences may reflect factors associated with hospitalization and discharge rather than a causal contrast. The record does not describe adjustment for those factors.

The registry describes follow-up GFR assessment at 1 year but does not report follow-up completion, missingness, or longitudinal results. It also does not describe eligibility criteria, the analytic population for each outcome, or how repeated measurements were modeled. The secondary outcomes are named, but their numerical findings are not reported.

Further details that would aid assessment—including the prespecified statistical plan, covariate strategy, multiplicity handling, and sample-size justification—are not reported in the registry record. The reported serious adverse event figures also lack details about timing, attribution, and overlap. These limitations constrain interpretation of both the main endpoint and the broader hypothesis about PICS and survival.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS — NCT02276066.
• Registry record last updated 2024-07-09; status last verified 2024-06.
• Results first posted 2024-07-09.
• 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

NCT02276066 is listed as a completed, non-randomized, single-group study sponsored by University of Florida, with enrollment of 73. The registry lists phase NA, no masking, a start date of 2015-02, and primary completion on 2023-05-20. The study concerns sepsis and the proposed relationship between kidney dysfunction, chronic critical illness, and PICS.

The primary endpoint is the baseline difference between measured GFR by Iohexol and calculated GFR from creatinine, in ml/min/1.73m2, summarized as a mean and standard deviation. Baseline measurement occurred at inpatient day 14 for participants still hospitalized or at discharge for those discharged earlier. Follow-up GFR assessment was described at 1 year. Iohexol was contraindicated for many patients.

The record describes 6 outcome measures and 1 analysis, and reports serious adverse event counts by hospitalization-status group. It does not report a numerical primary endpoint result, the endpoint analysis population, or key statistical analysis details. The hospitalization groups are not a like-for-like control comparison.