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 TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI) (NCT03477903), a randomized phase 2 study. The primary outcome is Average Daily Protein Adequacy Over the First 5 Days of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03477903 |
| Phase | Phase 2 |
| Condition | Critical Illness, Enteral Nutrition, Enteral Feeding Intolerance |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Millennium Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Critically ill participants developing enteral feeding intolerance (EFI). The registry record says the study enrolled participants at only 1 site and that 0 participants are reported for the primary outcome because of the risk of identifying a person.
Intervention
Intravenous TAK-954 was studied at 0.1 mg, 0.3 mg, and 1.0 mg. Each TAK-954 group also received normal saline injections. The listed schedule was once daily for TAK-954 and three times a day for saline, for a minimum of 5 days up to a maximum of 14 days.
Comparator
The fourth group received intravenous metoclopramide 10 mg three times a day along with a 100 mL normal saline infusion once daily. The registry describes a dose-ranging, parallel-group study, but no primary outcome results are reported for comparing the groups.
Primary question
Did average daily protein adequacy through enteral nutrition, measured over Days 1 to 5, differ across the study treatments? The registry defines adequacy as the percentage of the participant-specific protein target delivered per day, averaged across the 5 days. No participant-level primary outcome results or analyses are reported.
The study’s brief summary frames the question around improving the average daily protein adequacy received through enteral nutrition in critically ill participants developing EFI. Its official title describes a Phase 2b randomized, multi-center, double-blind, dose-ranging study of intravenous TAK-954, while the registry phase field lists PHASE2. The record identifies the study as terminated. It does not state why it was terminated, so the status alone does not establish the reason or what conclusions the sponsor drew.
3. Trial Design
The registry describes a randomized, parallel-group study with quadruple masking. Its official title calls it a Phase 2b, multi-center, double-blind, dose-ranging study; the phase field lists PHASE2. Four treatment groups are described: three TAK-954 dose groups and a metoclopramide group. The TAK-954 doses were 0.1 mg, 0.3 mg, and 1.0 mg, administered by intravenous infusion. Metoclopramide was administered intravenously at 10 mg. Saline was included in the treatment schedules described for the groups.
The TAK-954 regimens paired a once-daily 60 minute infusion with saline injections three times a day. The metoclopramide regimen paired injections three times a day with a once-daily 60-minute saline infusion. The stated treatment period was a minimum of 5 days up to a maximum of 14 days. The primary endpoint, however, covers Days 1 to 5; the record separately lists outcomes evaluated over the study treatment period and over the first 5 days.
The record gives enrollment as 1, identifies only 1 site, and reports that 0 participants are included in the primary outcome because of identification risk. It lists 8 outcome measures and 0 analyses. A registry status of terminated is recorded, with a start date of 2018-08-25 and a primary completion date of 2018-08-29. The reason for termination and any details about recruitment or study conduct are not reported in the registry record. The record also does not explain how randomization or masking was implemented, or provide a statistical analysis plan. Consequently, the design labels describe the intended structure, but the record does not permit an assessment of how fully that design was carried out or how treatment groups were analyzed.
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: One participant with a diagnosis of Enteral Feeding Intolerance (EFI) was enrolled and received 0.1 mg of TAK-954. No participants were enrolled in the other 3 planned arms of the study.
Overall Study
| Stage | TAK-954 0.1 mg |
|---|---|
| STARTED | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | TAK-954 0.1 mg |
|---|---|
| Study Terminated by Sponsor | 1 |
Analysis population for the primary outcome, as defined in the registry: Due to the low number of participants enrolled at only 1 site, 0 participants are reported due to the risk of identification of a person.
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.
| Characteristic | Unit | TAK-954 0.1 mg |
|---|---|---|
| Participants analysed | 1 | |
| Age, Continuous | years | — |
| Sex: Female, Male: Female | Participants | — |
| Sex: Female, Male: Male | Participants | — |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | — |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | — |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | — |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | — |
| Race (NIH/OMB): Asian | Participants | — |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | — |
| Race (NIH/OMB): Black or African American | Participants | — |
| Race (NIH/OMB): White | Participants | — |
| Race (NIH/OMB): More than one race | Participants | — |
| Race (NIH/OMB): Unknown or Not Reported | Participants | — |
| Region of Enrollment: United States | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Average Daily Protein Adequacy Over the First 5 Days of Treatment, measured over Days 1 to 5.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is average daily protein adequacy over the first 5 days of treatment, with a timeframe of Days 1 to 5. The registry defines daily protein adequacy as the percentage of the participant-specific target protein delivered through enteral nutrition. It is calculated as the ratio of actual protein achievement to the total target protein prescribed for that participant. The daily values across the 5 days are then averaged.
As a general statistical concept, an adequacy measure expresses delivered nutrition relative to an individual target, rather than recording only an absolute quantity. That framing can be useful when targets differ among participants: the endpoint asks how closely delivery met each participant’s prescribed goal. Averaging daily measurements creates a single summary across the specified treatment period, though it also means the resulting value does not by itself describe day-to-day variation or the timing of any change.
The record gives no unit, parameter type, or dispersion measure for the primary endpoint. Most importantly, it reports 0 participants for this outcome because reporting participant results could risk identifying a person. No primary endpoint values, group summaries, effect estimate, or uncertainty interval are reported. The endpoint definition therefore explains what was intended to be measured, but does not establish what was observed in any treatment group.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not provide a primary outcome result that can be interpreted as an estimate of treatment effect. It states that 0 participants are reported for the primary outcome because the low number enrolled at only 1 site could risk identifying a person. The record lists 0 analyses, and the primary-outcome reporting note indicates fewer than two arms in the primary outcome. There is therefore no reported group comparison on average daily protein adequacy over Days 1 to 5.
This absence of an interpretable comparison is different from a result showing no difference between treatments. No group values, contrast, confidence interval, or test result are reported. It is not possible to tell from the record whether the treatments produced similar or different protein adequacy, or how precise a treatment-effect estimate might have been. The study’s terminated status does not supply that missing information, and the registry record does not report a reason for termination.
The treatment schedules and the primary endpoint definition describe the intended comparison and measurement, not an observed clinical result. The registry lists three TAK-954 dose groups and a metoclopramide group, but it does not report primary outcome summaries across these groups. Although the study is described as dose-ranging, no dose-response pattern can be assessed from the information recorded for the primary endpoint.
The registry also lists secondary outcomes: average daily protein adequacy over the study treatment period; average daily change in 24-hour gastric residual volume over the first 5 days; average daily caloric adequacy; time to resolution of EFI; the percentages of participants achieving at least 80% of daily goal calories and protein; and the observed concentration of TAK-954 at the end of a dosing interval. The record does not provide analyses or results for these outcomes in the information available for this study. Their inclusion as planned outcomes should not be read as evidence that results were obtained or that any treatment effect was demonstrated.
The record includes sample-size planning assumptions based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not findings from a treatment comparison, and the record says the illustration is not the trial’s own design. Because no primary outcome result is reported, the planning framework cannot be used to infer efficacy, precision, or the ability of this study to detect an effect. It also cannot substitute for a reported estimate with uncertainty.
In statistical terms, the central limitation is not an imprecise estimate but the lack of a reported estimate. No inference about relative treatment performance follows from the endpoint definition, intervention descriptions, enrollment entry, or study status. The registry record supports a description of the intended question and the reporting limitation, but not a conclusion about the direction or magnitude of any treatment effect.
9. Statistical Methods Explained
Statistical methods help connect a study’s design to the conclusions that its data can support. In this record, the most important fact for interpretation is that no primary endpoint analysis is listed and no participant results are reported for that endpoint. The general concepts below explain what would ordinarily be needed to interpret a comparison; they are not claims about analyses performed in this trial.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. When implemented successfully, it aims to make the groups comparable, on average, with respect to measured and unmeasured characteristics at the time of assignment. This helps support a causal interpretation of a between-group comparison, subject to issues such as adherence, missing outcomes, and the analysis strategy. The registry labels this study randomized, but the method used to generate or conceal assignments is not reported in the registry record. Randomization by itself does not supply an effect estimate; results and an appropriate comparison are still required.
What do masking and a parallel-group design mean?
As a general concept, masking is intended to limit the influence of treatment knowledge on participants, clinical care, outcome assessment, or analysis. The record describes quadruple masking and also calls the study double-blind in its official title. It does not specify which groups of people were masked or how masking was maintained. A parallel-group design generally assigns participants to one treatment group and compares outcomes across groups, rather than having each participant receive each treatment in sequence. Here, four treatment groups are described. The registry’s primary outcome reporting note says fewer than two arms are represented in that outcome, so a primary between-group comparison cannot be interpreted from the record.
What would an effect estimate and confidence interval tell readers?
In general, an effect estimate summarizes the observed contrast between groups for a specified outcome. Its interpretation depends on the outcome scale and the exact comparison being made. A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis: narrower intervals generally indicate greater precision, while wider intervals indicate less precision. Neither can be interpreted without reported results. The record does not provide a primary effect estimate or confidence interval, so the size and precision of any treatment contrast are unknown.
Why can over-dispersion matter?
As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If an analysis ignores that extra variability, standard errors may be too small and confidence intervals or significance tests may give an overly optimistic picture of precision. The relevant concern depends on the outcome and model; for example, count outcomes may require methods that allow more variability than a basic count model assumes. The registry record does not report an analysis model for the listed outcomes, so it is not possible to say whether over-dispersion was relevant or how it was handled in this study.
What do the sample-size assumptions represent?
The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It frames the effect to detect as a stated fraction of the observed effect. The record explicitly distinguishes this illustration from the trial’s own design. In general, sample-size planning asks how much information would be needed to detect a specified effect under stated assumptions; it does not show that a study actually had that information or that the effect was present. Such calculations are planning illustrations, not observed power. The record does not report a sample-size justification for the trial or establish that these assumptions governed its design.
The record states that time-to-event planning figures use the total number of events under a Schoenfeld approach, while other planning figures use participants per arm. That distinction concerns how planning quantities are expressed; it does not create observed event counts or participant outcomes. With no primary outcome analysis reported, these assumptions cannot resolve the absence of an empirical comparison.
What can be concluded when analyses are not reported?
Statistical interpretation requires more than knowing which endpoint was intended. Readers generally need outcome summaries, the comparison or model used, an estimate of uncertainty, and enough information about the analysis population and missing data to assess the result. The registry lists 0 analyses and reports 0 participants for the primary endpoint due to identification risk. The analysis method, handling of missing values, and populations used are not reported in the registry record. Accordingly, standard statistical language about significance, precision, or robustness cannot be applied to a treatment contrast. The absence of reported analyses should not be translated into evidence of no effect, nor into evidence that an effect exists.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and multiple secondary outcomes, but it does not report a multiplicity strategy. In general, multiplicity arises when several outcomes, time points, treatment contrasts, or subgroup analyses are examined. Testing many questions can increase the chance of at least one apparently positive finding by chance. Methods to address that issue may include prespecifying a hierarchy or adjusting inference, but the approach used in this study is not reported in the registry record. Since no analyses are listed, there are no reported findings whose multiplicity adjustment can be assessed.
Missing-data procedures and analysis populations are also not reported in the registry record. It is not stated how incomplete outcome measurements, withdrawals, or deviations from assigned treatment would have been handled. Nor does the record identify an intention-to-treat, per-protocol, or other analysis population. These details matter in general because different choices can alter the participants contributing to an estimate and the meaning of the comparison.
The record says 0 participants are reported for the primary endpoint because the low number enrolled at only 1 site creates identification risk. This is a reporting restriction stated in the registry, not a description of how missing measurements were treated in a statistical analysis. The record gives enrollment as 1 but does not disclose primary outcome summaries or analyses. It therefore cannot support an assessment of the amount or pattern of missing data, the populations analyzed, or the consequences of any missingness for the treatment comparison.
11. What the Result Does, and Does Not, Mean
The study record documents an intended randomized comparison of intravenous TAK-954 dose groups with a metoclopramide group in critically ill participants with EFI. Its primary question concerns average daily protein adequacy through enteral nutrition over Days 1 to 5. The endpoint is defined in terms of actual protein achievement relative to each participant’s prescribed target, averaged across the specified days. These details clarify the research question and the measure chosen to address it.
They do not show whether one treatment resulted in higher protein adequacy than another. The registry reports 0 participants for the primary outcome because reporting at the low enrollment level could risk identifying a person, and it lists 0 analyses. No group summaries, treatment contrasts, uncertainty intervals, or test results are available in the record. Thus, neither benefit nor lack of benefit can be inferred from the reported primary outcome information.
The terminated status likewise does not explain what happened to the study or why it ended. The reason for termination is not reported in the registry record. The listed secondary outcomes indicate additional questions the study was designed to address, but no results for them are reported in the information recorded. Listing an outcome is not equivalent to reporting a finding.
In general, a study’s design and endpoint definition can help readers judge what a reported estimate would mean, while its numerical results and analysis methods are needed to judge the evidence. In this case, the record supports a description of the planned design and the privacy-related limit on outcome reporting. It does not support a conclusion about the direction, size, precision, or clinical importance of a treatment effect.
12. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical statistics: a clear research question and a detailed endpoint definition do not, on their own, provide evidence about the answer. The record describes a randomized dose-ranging design, four treatment groups, and a protein adequacy outcome tied to participant-specific nutrition targets. Yet its primary outcome reporting note says 0 participants are reported because of identification risk, and the record lists 0 analyses. Readers can identify what was intended to be compared without being able to estimate how the groups differed.
It also shows why registry status and outcome reporting need to be interpreted separately. The study is marked terminated, but the registry does not state why. The status does not reveal whether the trial ended early for operational, scientific, safety, or other reasons. Assigning a cause or inferring a result from the status would go beyond what the record reports.
For statistical practice, the record highlights the role of transparent analysis details. Interpretation ordinarily depends on the analysis population, missing-data approach, specified comparisons, and uncertainty around estimates. Those methods are not reported. The planning assumptions are explicitly described as an illustration rather than the trial’s design and cannot stand in for observed results.
The most defensible statistical conclusion is therefore limited but useful: the study’s intended question and measurement are documented, while the primary outcome comparison is not available for interpretation in the registry record. Recognizing that boundary prevents a design description from being mistaken for a treatment-effect finding.
13. 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 main trial-specific limitation for interpretation is the absence of reportable primary outcome results. The registry states that 0 participants are reported for the primary endpoint because only 1 site enrolled a low number of participants and reporting could risk identifying a person. Enrollment is listed as 1, but the record does not provide outcome values or group summaries. The primary outcome reporting note also indicates fewer than two arms in that outcome, and the record lists 0 analyses. No treatment contrast or its precision can therefore be assessed.
The study is marked terminated, but its reason for termination is not reported in the registry record. The record does not explain whether the planned design was completed, how many participants were assigned to each group, or how treatment exposure and follow-up proceeded. Those details should not be inferred from the enrollment entry or status.
The statistical plan is not reported in the registry record. This includes the method for handling missing outcomes, the analysis populations, the exact treatment comparisons, and any approach to multiplicity across the primary and secondary outcomes. The record describes sample-size assumptions for a planning illustration, but says that illustration is not the trial’s own design. It does not provide the trial’s sample-size justification.
Although secondary outcomes are listed, their analyses and results are not reported. The listed endpoint definitions and treatment schedules clarify what was planned, but do not resolve these reporting limitations or establish any outcome for this study.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI) — NCT03477903.
- Registry record last updated 2019-09-24; status last verified 2019-09.
- Results first posted 2019-09-24.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
17. Record Summary
The registry describes a randomized, parallel-group, quadruple-masked study of intravenous TAK-954 in critically ill participants developing EFI. Its official title describes a Phase 2b, multi-center, double-blind, dose-ranging study; the phase field lists PHASE2. Three TAK-954 doses were compared with a metoclopramide regimen, with treatment scheduled for a minimum of 5 days up to a maximum of 14 days.
The primary endpoint was average daily protein adequacy over Days 1 to 5, defined relative to each participant’s prescribed protein target. The record gives enrollment as 1 and states that 0 participants are reported for the primary outcome because of identification risk at only 1 site. It lists 0 analyses and marks the study terminated. The reason for termination and the primary outcome results are not reported in the registry record. Consequently, the record describes the intended comparison but does not permit interpretation of a treatment-effect estimate.