Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide (NCT00356265), a non-randomized na study. The primary outcome is α1-adrenoceptor Vasoreactivity With L-NMMA.

2. Clinical Question

3. Trial Design

This was a non-randomized, unmasked, parallel-group study sponsored by the University of Michigan. Its listed groups were people with chronic kidney disease, people with hypertension, and people with normal blood pressure. The registry reports an enrollment of 18 and classifies the phase as not applicable. Because assignment was not randomized, the groups should be understood as observationally assembled comparison groups rather than treatment arms created by random allocation. The registry cautions that they are not a like-for-like control comparison.

The study description outlines screening with a physical examination, ECG, and laboratory tests. It says that some participants with high blood pressure might stop their regular blood pressure medication for three weeks before the inpatient study. It also describes intra-arterial medications intended to change blood-vessel responses and a GFR test to confirm renal function in the chronic kidney disease group. The listed intervention is regional phenylephrine arterial infusion. The primary endpoint title also refers to L-NMMA, but further procedural detail is not reported in the registry record.

The study began in 2006-07, had a primary completion date of 2010-11, and is recorded as terminated. The primary-outcome description says that data from 12 participants formed the basis for the outcome information and that the two hypertensive participants' data were not analyzed because of early termination. It does not explain the relationship between those figures and the overall enrollment, or describe the analysis status of every participant. The protocol's reason for termination is not reported in the registry record. A detailed statistical analysis plan, including planned group contrasts and covariate adjustment, is also not reported in the registry record.

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: Based on the data from the 12 participants, and the early termination, no analysis was performed on the two hypertensive participants' data.

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 α1-adrenoceptor Vasoreactivity With L-NMMA, measured over up to 8 hours.

The primary endpoint is α1-adrenoceptor vasoreactivity with L-NMMA. The registry defines vasoreactivity using a forearm blood-flow dose-response curve: forearm blood flow in milliliters per minute per log of phenylephrine, also described as FABF ml/min/logPE. The endpoint is reported as a mean of a continuous measure, with standard error as its stated dispersion. Its timeframe is up to 8 hours.

A dose-response measure describes how an observed response varies across doses or concentrations. In general, measuring vascular response across a dose range can characterize reactivity more fully than recording a single response at one exposure. The registry describes the plotted axes as ml/min and log phenylephrine concentration, while its endpoint unit expresses blood flow per log of phenylephrine. This is the measure the study identifies for examining α1-adrenoceptor vascular responsiveness in the groups.

The registry's scientific rationale is to investigate mechanisms related to enhanced α1 vasoreactivity in progressive renal disease, with attention to endothelial nitric oxide. The endpoint is therefore a physiological measure, not a patient-centered clinical outcome. Its presence alone does not establish a difference among groups or explain a mechanism. No endpoint means, standard errors, group contrasts, confidence intervals, or p-values are reported in the registry record, so the size and precision of any observed response cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous and is summarized in the registry as a mean with standard error. A mean describes the central value of observations on a quantitative scale. A standard error describes the precision of an estimated mean under a statistical model; it is not the spread of individual observations. In general, the standard error becomes smaller when an estimate is based on more informative observations, though its value also depends on variability. The registry does not provide the mean or standard error for this endpoint, so neither the observed response nor the precision of its estimate can be assessed.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with an estimate under a specified procedure and assumptions. It helps readers judge precision, rather than relying only on whether a statistical test crosses a significance threshold. For this study, no confidence interval is reported in the registry record. Because the numerical estimate and its uncertainty are absent, a confidence interval cannot be described or reconstructed from the endpoint definition. The record also does not state a confidence-interval method.

What does a group comparison require?

A comparison of means needs a clearly defined contrast, such as the difference between two specified groups, together with an estimate and its uncertainty. Here, the registry describes three groups but does not report the endpoint means or a group contrast. It does not specify whether the primary question was to compare all groups jointly, make selected pairwise comparisons, or use another contrast. That comparison strategy is not reported in the registry record. No conclusion about the direction or size of a contrast can be made without those results.

The study is non-randomized. In general, random allocation helps balance measured and unmeasured characteristics between groups on average; a non-randomized comparison does not have that design protection. Group differences may therefore reflect factors other than the measurement under study. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured confounding. The registry does not report an adjusted model or covariates used for analysis. Its caution that the groups are not a like-for-like control comparison is consistent with interpreting any hypothetical contrast carefully.

How should the endpoint scale be read?

The stated unit is ml/min x 1/log[PE], and the description identifies forearm blood flow across a phenylephrine dose-response curve. The measure is intended to characterize vascular reactivity in the study context. In general, units matter because they define what a numerical estimate represents and what comparisons are meaningful. The endpoint description gives a scale, but without reported estimates, readers cannot determine whether any response was large or small on that scale. The record does not report a threshold for a clinically or physiologically important difference.

The endpoint's dispersion is given as standard error, rather than standard deviation. In general, a standard deviation describes variability among observations, whereas a standard error describes uncertainty in an estimated quantity. They answer different questions. A reported standard error should not be read as showing the range of individual participant responses. Because no numerical standard errors are posted, the variability and precision cannot be quantified from the registry record.

What does the analysis status tell readers?

The record says its primary-outcome information was based on data from 12 participants and that data from two hypertensive participants were not analyzed following early termination. It lists no analyses. Those statements do not supply a statistical test, estimate, or explanation of the analysis population. The record does not report whether the endpoint was analyzed separately by group, whether any model assumptions were checked, or whether missing observations were imputed. These details should not be inferred from the outcome's continuous-measure classification.

In general, a statistical test evaluates data against a null hypothesis under specified assumptions. A p-value, if reported, would describe how unusual the data are under that model and null hypothesis; it would not by itself measure the size or importance of a group difference. No p-value or test is reported for this endpoint. Likewise, no model form or variance assumptions are reported, so no claims about the method of inference are warranted.

There is no reported sample-size justification or trial-specific power calculation in the registry record. A planning calculation based on an observed effect would be a hypothetical illustration, not observed power and not evidence that the study could reliably detect a particular effect. In general, planning calculations depend on assumptions about the effect of interest, variability, allocation, and analysis. The registry record does not provide the endpoint estimates needed to assess an effect-based planning illustration. Its termination and the absent analysis results further mean that no statistical power conclusion should be drawn from the enrollment figure alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and no analyses. It does not report how many outcomes or contrasts were designated primary in the protocol, whether the listed outcomes were tested, or whether any multiplicity adjustment was planned or used. When multiple outcomes or comparisons are tested, the chance of at least one apparently notable result can increase; in general, prespecified hypotheses and multiplicity procedures help readers understand how such testing was handled. No correction method or testing hierarchy is reported in the registry record, so none should be assumed.

The registry says that the primary-outcome information was based on data from 12 participants and that the two hypertensive participants' data were not analyzed because of early termination. It does not report a complete accounting of missing endpoint observations, reasons for missingness beyond that statement, or how missing data were handled. It also does not state whether any imputation, sensitivity analysis, or complete-case rule was used. These details are not reported in the registry record.

The analysis population is not fully specified. The registry does not describe an intention-to-treat population, a per-protocol population, or another prespecified analysis set. Since allocation was non-randomized, the terminology of intention-to-treat should not be presumed to apply in the same way as in a randomized trial. The record's enrollment figure and its statement about the endpoint data do not establish which participants contributed to each analysis. Without a defined denominator and analysis set, the completeness and representativeness of an endpoint analysis cannot be assessed.

Early termination is relevant to interpretation because the record explicitly links it to the lack of analysis of the two hypertensive participants' data. The reason for termination, whether any interim analysis occurred, and whether termination followed a prespecified rule are not reported in the registry record. No conclusions about the effect of stopping on the estimates can be drawn without those details or numerical results.

11. Safety Results

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

Other (non-serious) adverse events

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

The registry reports adverse-event counts separately for the chronic kidney disease, hypertension, and normotensive groups. For serious adverse events, the reported affected counts are 0 among 7 at risk in the chronic kidney disease group, 0 among 2 at risk in the hypertension group, and 0 among 6 at risk in the normotensive group. For other adverse events, the corresponding reported affected counts are also 0, with at-risk counts of 7, 2, and 6, respectively. These are the registry's group-specific counts, not a substitute for the primary vascular-response outcome.

A zero reported count means that no events of that category were recorded among the participants represented by the stated at-risk count in that group. In general, a zero count does not establish that an event is impossible, and it does not by itself quantify the risk that would be seen in a larger or different population. The group sizes represented in these safety entries are limited, and the registry does not provide uncertainty intervals for the event counts.

Deaths are recorded as null rather than as a numerical count. A null entry is not the same as a reported zero; deaths are not reported in the registry record. The registry also lists no top serious adverse-event terms. These safety entries should therefore be read narrowly as the adverse-event counts posted for the listed groups, without inferring broader safety conclusions.

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

The study addresses vascular reactivity in groups with chronic kidney disease, hypertension, and normal blood pressure. The registry identifies a physiological primary endpoint based on forearm blood-flow response to phenylephrine, with L-NMMA named in the endpoint. This helps define the scientific question and the kind of measurement collected. It does not establish what the results were.

The posted record does not include numerical endpoint estimates, a group comparison, an uncertainty interval, or a statistical test. Therefore it does not show whether the groups differed, how large any difference might have been, or how precisely it could be estimated. The absence of a posted result should not be interpreted as a finding of no difference, just as the study's biological rationale should not be treated as evidence that a difference was present.

The design also shapes what the study could establish. Groups were not randomized, masking was absent, and the registry cautions that the groups are not a like-for-like control comparison. In general, observed differences in non-randomized groups can reflect both the measure of interest and other group characteristics. The record does not describe adjusted analyses that might address measured differences. No causal treatment effect can be inferred from the design description.

The record reports early termination and states that data from two hypertensive participants were not analyzed. It does not give the reason for termination or a complete account of the endpoint analysis population. Those limitations make it especially important not to infer a completed group comparison from the study's enrollment or outcome definition alone. Enrollment describes the study record, not the number contributing to a specific endpoint analysis.

In short, the registry provides context about the question, design, measurement, and some safety counts, but it does not report the primary numerical result. The evidence available in the record is insufficient to estimate the magnitude or direction of vascular-response differences. It also cannot establish whether the proposed mechanism is supported or refuted. Those conclusions would require reported endpoint data and a clear account of the analysis.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a well-described research question and a reported result. The registry names a continuous physiological endpoint, gives its unit and dispersion measure, and describes three comparison groups. Yet it does not post the endpoint estimates or an analysis of the group differences. A measurement definition alone cannot answer a comparative question; the estimate, its uncertainty, and the analysis population are needed to evaluate the evidence.

The non-randomized design is another important feature. In general, comparisons between naturally defined groups can be useful for describing patterns, but they do not automatically isolate the effect of one factor from other differences between groups. A clear account of group composition and any adjustment strategy is important for interpreting such comparisons. The registry cautions that these groups are not a like-for-like control comparison, and it does not report an adjusted analysis.

The early termination note also illustrates why participant flow and analysis status matter. The registry says that data from 12 participants formed the basis of the primary-outcome information and that the two hypertensive participants' data were not analyzed. Without group-specific endpoint estimates and a full account of the analysis set, readers cannot judge whether the primary comparison was completed as intended. The reason for termination and any consequences for the planned analysis are not reported.

Finally, the safety entries and primary endpoint answer different questions. Adverse-event counts describe recorded safety events in the listed groups; they do not provide evidence about the magnitude of vascular reactivity. Keeping these kinds of outcomes distinct is essential to a sound statistical reading. The record's main statistical lesson is that design, measurement, analysis population, and uncertainty all matter—and missing numerical results cannot be replaced by biological rationale or by counts from another outcome.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the research question is the absence of reported endpoint estimates and inferential results. The registry defines the outcome but gives no group means, standard errors, contrasts, confidence intervals, or p-values. Consequently, there is no numerical basis for judging the direction, magnitude, or precision of a group difference. The record also does not state a threshold for an important difference on the endpoint scale.

The study was non-randomized and unmasked. The registry itself cautions that the groups are not a like-for-like control comparison. It does not report participant characteristics, a covariate-adjustment plan, or an adjusted result. As a result, even a reported difference would need careful interpretation in light of possible differences between groups. No causal conclusion is supported by the design description alone.

Early termination further limits interpretation. The record says that data from two hypertensive participants were not analyzed, but the reason for termination and the implications for the planned analysis are not reported in the registry record. It does not give a full participant flow or specify the endpoint analysis population. Although enrollment is listed as 18, that figure does not establish how many participants contributed to each endpoint analysis.

Important statistical details are also absent: the planned comparison, model, treatment of missing data, multiplicity approach, and any interim-analysis procedure are not reported in the registry record. The primary outcome is summarized by mean and standard error, but no numerical summaries are posted. Deaths are null in the safety entries, which is not the same as a reported zero. Together, these gaps prevent a complete assessment of both the primary result and the study's analysis process.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide — NCT00356265.
• Registry record last updated 2018-01-23; status last verified 2017-12.
• Results first posted 2018-01-23.
• 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 describes a University of Michigan, non-randomized, unmasked, parallel-group study of chronic kidney disease, hypertension, and normal blood pressure. It lists an enrollment of 18, a start date of 2006-07, a primary completion date of 2010-11, and a terminated status. The primary endpoint is α1-adrenoceptor vasoreactivity with L-NMMA, defined using forearm blood-flow response across phenylephrine concentrations and summarized as a mean with standard error.

The outcome description says the data were based on 12 participants and that data from the two hypertensive participants were not analyzed because of early termination. Numerical primary results and inferential analyses are not reported in the registry record. The safety entries report no serious or other adverse events in the listed at-risk counts for the three groups; deaths are not reported as a numerical count. Overall, the record describes the study question and design but does not provide enough endpoint results to assess the primary group comparison.