Alvimopan as a Rescue Treatment of Postoperative Ileus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Alvimopan as a Rescue Treatment of Postoperative Ileus (NCT04405037), a randomized phase 4 study. The primary outcome is Hospital Length of Stay.

2. Clinical Question

The clinical question is about treatment after postoperative ileus develops, rather than prevention of ileus in all patients undergoing surgery. This distinction matters because the registry describes randomization at the time of diagnosis. The primary endpoint is the interval from that diagnosis to discharge, while the posted secondary outcomes include return of bowel function, re-operation, and re-admission. The listed secondary results include re-operation and re-admission; a result for time to return of bowel function is not reported in the registry record.

The study description also identifies cost effectiveness, safety, and effectiveness in reducing length of stay and ileus duration as aims. However, the posted results summarized in the registry record do not provide a cost-effectiveness result or a numerical result for ileus duration. The available estimates therefore address only some parts of the broader stated aims. The clinical question should be read in that narrower context: a comparison of the posted hospital-stay outcome and selected subsequent events between randomized treatment groups, in patients who had already developed postoperative ileus.

3. Trial Design

The registry describes a prospective, randomized, parallel-group trial with no masking and a phase 4 designation. It concerns patients who develop postoperative ileus following colorectal or small bowel resection, including the specified ileostomy reversal procedure. Participants were to be randomized at diagnosis to alvimopan rescue therapy or conservative standard care. The record lists an enrollment of 65 and a completed status. The brief study description separately states a plan for a total of 58 patients, 29 in each group. These are both recorded details; the registry record does not explain the difference between the enrollment figure and the planned total in the summary.

The posted primary outcome groups contain 31 participants in the alvimopan group and 32 in the control group. The treatment description specifies oral alvimopan at 12mg, with doses 12 hours apart and a maximum of 3 doses. Control care is described as an ERAS pathway including NPO status, IV fluids, nasogastric decompression, early feeding and ambulation, and opioid-minimizing measures. The registry gives the study start as 2020-08-01, primary completion as 2024-04-02, and status as completed.

The primary endpoint is hospital length of stay, defined as days from postoperative ileus diagnosis until discharge, with a timeframe of up to 30 days. The registry lists the outcome parameter as a mean and the dispersion as an inter-quartile range. The posted group values are 5.0 for alvimopan and 6.0 for control, with accompanying ranges of 3.5 to 6.5 and 5.0 to 8.0, respectively. No primary between-group analysis is reported in the registry record. The registered outcome list also includes time to return of bowel function, re-operation, and re-admission, but numerical results are posted only for re-operation and re-admission among those secondary outcomes.

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:

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: Intent to Treat

6. Primary Endpoint

The registry lists the primary outcome as Hospital Length of Stay, measured over up to 30 days.

Hospital length of stay is measured from the diagnosis of postoperative ileus until discharge from hospital. It is therefore a measure of the time spent in hospital after the complication has been diagnosed, not the total admission from surgery. The registry specifies a timeframe of up to 30 days. This endpoint is relevant to the stated study aims because the brief summary identifies length of stay as an outcome of interest and describes alvimopan as rescue therapy after ileus develops.

The registry labels the endpoint as a mean in days and lists the inter-quartile range as its dispersion measure. The posted value is 5.0 days for the alvimopan group, with an inter-quartile range from 3.5 to 6.5, and 6.0 days for the control group, with an inter-quartile range from 5.0 to 8.0. The inter-quartile range describes the spread of the observed values; it is not a confidence interval for the group mean. The record does not provide a standard error, confidence interval, p-value, or reported statistical comparison for this primary endpoint.

Length of stay can reflect several influences on discharge timing, not only bowel function. The endpoint itself does not separate those influences. Interpretation should therefore stay close to its definition: days from ileus diagnosis to discharge, as recorded for each group, with no posted inferential comparison. A numerical difference between the group summaries is descriptive unless accompanied by an analysis that quantifies uncertainty and supports a comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a group summary convey?

A group summary condenses observed outcomes into a value that is easier to compare across groups. For the primary endpoint, the registry lists a mean and an inter-quartile range. The mean gives a summary of the group’s recorded length of stay, while the inter-quartile range describes the middle spread of the observations. These quantities answer different questions. Neither the inter-quartile range nor the difference between two group summaries is, by itself, a confidence interval for the treatment effect.

The posted primary values are 5.0 days and 6.0 days. The associated inter-quartile ranges are 3.5 to 6.5 and 5.0 to 8.0. The registry does not report an inferential comparison for this endpoint. Without a standard error or confidence interval for the between-group contrast, the precision of that contrast cannot be assessed from the posted result. The summary values should not be treated as proof of a treatment effect or as proof that there is no effect.

How should a confidence interval be read?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method. It gives a range of values compatible with the observed data and the method used; it is not a range containing a fixed proportion of individual outcomes. The secondary endpoint intervals are reported for risk differences. For re-operation, the interval is -0.007 to 0.201; for re-admission, it is -0.124 to 0.263. Both include zero, the value corresponding to no risk difference. Their breadth also signals that the estimates are not precise. An interval including zero does not establish that the groups are equivalent.

The registry's risk differences compare the observed event frequencies between the alvimopan group and the control group. A positive estimate indicates a higher observed event frequency in the alvimopan group under that direction of comparison. For re-operation, the estimate is 0.097; for re-admission, it is 0.070. The intervals show substantial uncertainty around both estimates. The reported values are unadjusted, so they are not adjusted for other characteristics or for multiple outcome testing.

What does a p-value say?

In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The re-operation comparison has p = 0.071, and the re-admission comparison has p = 0.482. These values should be read alongside the corresponding estimates and confidence intervals. The confidence intervals convey the range of effect sizes compatible with the data, while p-values provide a test against a particular null value.

The registry reports no primary p-value and no reported analyses for the listed secondary outcomes. The secondary comparison results are therefore not described as sponsor-reported adjusted analyses. There is no basis in the registry record to claim a particular model, covariate adjustment, or testing strategy for these comparisons.

Why do planning illustrations depend on the assumed effect?

The planning illustration for re-admission uses the observed effect as its starting point and describes participant requirements per arm for 80% and 90% power at the stated two-sided significance level of 0.05. It uses equal allocation and a normal approximation. Its scenarios consider 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The corresponding participants per arm for 80% power are 501, 859, and 1,862; for 90% power, they are 670, 1,150, and 2,491.

These are planning illustrations, not the trial’s original sample-size justification and not observed power. The registry explicitly describes them as computed from the observed effect rather than from the trial's own design. A smaller effect assumption requires a larger planned group size to achieve the same target power, all else equal. This general relationship helps explain why the estimates increase across the listed scenarios; it does not establish that the true effect is any particular fraction of the observed estimate. The registry record does not report the trial’s sample-size justification.

What do the methods not resolve?

For outcomes such as re-operation and re-admission, event counts are relatively small, and the resulting estimates are uncertain. In general, sparse outcomes can yield unstable effect estimates and wide intervals. The posted results are unadjusted, and the registry record does not identify a prespecified statistical analysis plan, missing-data method, analysis population, or multiplicity procedure. Those omissions limit assessment of whether the reported comparisons match the intended analysis and how the number of tested outcomes was handled.

The registry reports an outcome parameter and dispersion type for hospital length of stay, but not the method used for a primary comparison. It also does not report a numerical analysis for time to return of bowel function or a cost-effectiveness analysis. No additional statistical conclusions should be inferred for those aims. The most defensible reading distinguishes the descriptive primary summaries, the unadjusted secondary comparisons, and the planning calculations, because each answers a different question and carries different uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity procedure for the primary and secondary outcomes. Multiplicity arises when several outcomes or comparisons are examined: the more tests that are made, the greater the chance that at least one result appears unusual even if there is no underlying effect. In general, a prespecified strategy can control how this risk is handled, but no such strategy is reported in the registry record. The secondary p-values should therefore be regarded as unadjusted and interpreted cautiously, rather than as confirmatory evidence considered in isolation.

The record also does not report a missing-data method or the extent of missing outcome data. It is therefore not possible to determine from the registry whether all randomized participants contributed to each outcome, how incomplete observations were handled, or whether any sensitivity analysis was used. The posted group sizes are available for the reported outcomes, but the registry does not explain how those denominators relate to an analysis population or whether all participants had complete follow-up.

An intention-to-treat analysis, a per-protocol analysis, or another analysis population is not identified in the registry record. Nor does the record describe a prespecified primary analysis, covariate adjustment, or handling of protocol deviations. These details matter because they clarify which participants and observations contribute to an estimate and whether the analysis follows the original random assignment.

The registry lists a completed study and posts some outcome data, but a full statistical analysis plan is not reported in the registry record. The absence of these details does not demonstrate that procedures were not used; it means they cannot be assessed from the registry record. Consequently, the scope of missingness, potential selection in the reported analyses, and the treatment of multiple outcomes remain uncertain. These limitations reinforce the need to distinguish the descriptive results from a fully documented confirmatory analysis.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts are zero in the alvimopan group and zero in the control group. The registry lists 31 participants at risk in the alvimopan group and 32 in the control group for these figures. Deaths are also recorded as zero in each group. No serious adverse-event terms are listed in the registry record.

These figures describe what was recorded during the trial; they do not show that the possibility of serious harm is absent. With no serious events recorded, the trial cannot estimate a comparative serious-event effect from these counts. The registry also reports other adverse events for 10 participants in the alvimopan group and 13 in the control group, among 31 and 32 participants at risk, respectively. These are counts, not a formal adjusted safety comparison.

Safety interpretation depends on how events were defined, collected, followed, and attributed. Those details are not reported in the registry record. The adverse-event information should therefore be read as a limited description of recorded events in the trial groups, not as a comprehensive safety assessment or a general conclusion about risk.

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

The posted results describe a randomized comparison of alvimopan rescue therapy with conservative standard care in patients who developed postoperative ileus after specified bowel surgery. For the primary endpoint, the registry reports group summaries for days from ileus diagnosis to discharge, along with inter-quartile ranges. It does not report a primary between-group estimate, confidence interval, or p-value. The numerical summaries alone cannot establish how precisely the groups differ or whether the observed contrast is compatible with chance variation.

The secondary results provide unadjusted estimates for re-operation and re-admission. Both confidence intervals include no difference and allow effects in either direction. These results do not establish equivalence, and they do not provide a precise estimate of a treatment effect. The registry contains no numerical result for time to return of bowel function, despite listing it as a secondary outcome. Nor does it post a cost-effectiveness result, although cost effectiveness is part of the study's stated aim.

The adverse-event counts are descriptive. Zero serious adverse events and zero deaths are recorded in each group, but these figures do not demonstrate that serious risks are absent. The record does not provide enough information about event collection or a formal comparative safety analysis to support a broader safety conclusion.

More generally, trial results apply most directly to the participants and care setting represented in the study. The registry record does not give enough detail to assess the full analysis population, missing data, multiplicity, or the primary statistical method. These gaps make it important to avoid turning descriptive group values or unadjusted secondary comparisons into a definitive claim about benefit, lack of benefit, or safety. The posted results document what was recorded; they do not by themselves settle the clinical question.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between reporting group summaries and reporting a treatment-effect analysis. The registry posts a primary outcome value and inter-quartile range for each group, but no primary contrast or measure of its uncertainty. Readers can describe the observed length-of-stay summaries, but cannot use the registry record to assess the precision of a primary treatment effect.

The secondary outcomes show why effect estimates need to be considered together with uncertainty. The re-operation and re-admission estimates are accompanied by confidence intervals that include no difference and extend across a range of possible effects. Their p-values alone would omit that information. The unadjusted nature of the comparisons and the absence of a reported multiplicity plan further limit confirmatory interpretation.

The record also makes a useful distinction between observed results and planning illustrations. The re-admission planning scenarios are derived from the observed effect, not from the trial's original design. They show how assumed effect size affects planning requirements under stated assumptions, but they are not observed power and do not establish a suitable sample size for a future study. The registry does not report its original sample-size justification.

Finally, the registry's stated aims are broader than the numerical outcomes posted. Results for some listed outcomes are absent, and the analysis population and missing-data approach are not reported. This combination highlights why transparent outcome reporting, analysis methods, and uncertainty estimates are essential for interpreting randomized trials. The available record supports a careful description of selected outcomes, while leaving important questions about the planned and completed analyses unresolved.

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.

A specific limitation is the discrepancy between the registry enrollment of 65 and the brief study description's planned total of 58, with 29 in each group. The registry record does not explain the difference. The posted primary outcome group sizes are 31 and 32, but the record does not clarify how these figures relate to the planned total or whether all participants randomized were included in each analysis. This limits reconstruction of participant flow.

The registry reports a primary mean and inter-quartile range but no primary comparison estimate or uncertainty interval. It is not possible to assess the statistical precision of the primary contrast or determine the analysis method used. The record does not report whether the mean was adjusted or unadjusted, or how any skewness in length of stay was addressed.

The secondary comparisons are unadjusted and the registry does not report a multiplicity procedure. The event counts are limited, and the intervals for both secondary risk differences are broad. No numerical result is posted for time to return of bowel function, and no result is posted for cost effectiveness or ileus duration. This leaves several stated study aims without results in the registry record.

Further limitations are that the analysis population, missing-data methods, follow-up completeness, and statistical analysis plan are not reported in the registry record. The trial is listed as unmasked, and no information is reported about outcome adjudication or potential differences in discharge decisions. These matters could affect the interpretation of outcomes, especially hospital length of stay. The registry record alone cannot establish how these issues were handled or how representative the trial participants are of other clinical settings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Alvimopan as a Rescue Treatment of Postoperative Ileus — NCT04405037.
• Registry record last updated 2025-08-20; status last verified 2025-08.
• Results first posted 2025-08-20.
• 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 lists NCT04405037 as a completed, randomized, parallel-group phase 4 trial with no masking. The study evaluates alvimopan as rescue treatment for postoperative ileus following colorectal or small bowel surgery. The stated enrollment is 65; the brief study description separately gives a planned total of 58, with 29 in each group. The registry gives a study start of 2020-08-01 and primary completion of 2024-04-02.

The primary outcome is hospital length of stay from postoperative ileus diagnosis until discharge, with a timeframe of up to 30 days. The posted group summaries are 5.0 days for alvimopan and 6.0 days for control, with inter-quartile ranges of 3.5 to 6.5 and 5.0 to 8.0. No primary comparison is reported in the registry record. Posted secondary comparisons cover re-operation and re-admission; a numerical result for time to return of bowel function is not reported in the registry record.

Serious adverse events and deaths are recorded as zero in both groups. Other adverse events are recorded for 10 participants in the alvimopan group and 13 in the control group. The registry record does not report a multiplicity plan, missing-data method, analysis population, or primary statistical analysis method.