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 Nesiritide Use Following Cardiac Surgery in Infants (NCT00281671), a randomized phase 1, phase 2 study. The primary outcome is Urine Output.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00281671 |
| Phase | Phase 1, Phase 2 |
| Condition | Heart Defects, Congenital, Cardiopulmonary Bypass |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 9 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Boston Children's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Infants following cardiopulmonary bypass. The registry record lists congenital heart defects and cardiopulmonary bypass as conditions and records enrollment of 9 participants.
Intervention
Nesiritide infusion for 10 hours as part of a crossover sequence, with a two hour washout between study-drug periods.
Comparator
Placebo infusion for 10 hours. Each participant was randomly assigned to receive nesiritide and placebo in one of the two possible sequences.
Primary question
What was urine output, measured in cc/kg/hr during the last 5 hours of study-drug infusion, under nesiritide and placebo?
The study was designed to examine the effects of nesiritide on urine output and hemodynamics after cardiopulmonary bypass in infants. The registry description also identifies safety and pharmacokinetic data as study aims. The posted primary outcome focuses specifically on urine output, while cardiac index and the number of participants with hypotension and bradycardia are listed as secondary outcomes.
Because this is a crossover study, the treatment comparison concerns measurements under both study drugs in the same participants, rather than separate groups of infants who received only one treatment. The two sequences were randomized. This design can help account for stable differences between participants, but interpretation also depends on how the measurements are analyzed and on whether period or carryover effects are addressed. Those analysis details are not reported in the registry record.
3. Trial Design
The registry record describes a randomized, quadruple-masked crossover pilot study of nesiritide and placebo after cardiopulmonary bypass in infants. It lists the study as Phase 1 and Phase 2, with enrollment of 9 participants, and records the status as terminated. The sponsor is Boston Children's Hospital.
Participants were randomly assigned to one of two treatment sequences. In either sequence, they received an infusion of one study drug for 10 hours, had a two hour washout period, and then received the other study drug for 10 hours. The descriptions of the two arms specify the same crossover schedule, with the sequence differing according to the initial assignment. Thus, the placebo and nesiritide results are treatment-period results from a crossover design; the registry enrollment figure is 9, not a total obtained by adding the two treatment-period counts.
The stated primary outcome was urine output during the last 5 hours of study-drug infusion. Its unit is cc/kg/hr, and the result is summarized by a median and full range for each treatment. The registry also lists three secondary outcomes: participants with hypotension and bradycardia, urine output, and cardiac index. It identifies four outcome measures in total.
The registry record does not report why the study was terminated, the planned or actual timing of each participant's treatment periods, or a detailed statistical analysis plan. Details about how masking was maintained and whether it was assessed are not reported in the registry record. The stated design features describe the intended comparison, but do not establish how every design issue was handled in the analysis.
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
| Stage | Nesiritide First, Then Placebo | Placebo First, Then Nesiritide |
|---|---|---|
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
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 | All Study Participants |
|---|---|---|
| Participants analysed | 9 | |
| Age, Continuous | days | 6 (4 to 103) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 6 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: United States | participants | 9 |
| Weight | Kg | 3.5 (2.5 to 4.9) |
| Prematurity | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Urine Output, measured over 5 hours.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | cc/kg/hr |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is urine output measured in cc/kg/hr during the last 5 hours of the study-drug infusion. The registry description specifies that the measure is taken during that part of the infusion period, rather than across the entire study or over a longer follow-up interval. The posted values are medians with full ranges for the placebo and nesiritide periods.
Urine output is a direct measurement of the volume of urine produced relative to body weight and time. In this study, it was selected to address the stated question about the effects of nesiritide after cardiopulmonary bypass. The registry also names hemodynamics, safety, and pharmacokinetic data as study interests, but the primary endpoint itself is urine output; it should not be treated as a direct measure of all those other domains.
A median describes the middle of the observed values when they are ordered. The full range gives the lowest and highest observed values, so it indicates the spread between the extremes but does not show how values are distributed between them. With a pilot enrollment of 9 and a crossover design, the treatment-period summaries provide a compact description of the observations. By themselves, they do not show the participant-level paired differences or quantify the uncertainty in a treatment contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results give a median urine output of 2.9 cc/kg/hr for placebo, with a full range of 1.1 to 7.1, and a median of 3.1 cc/kg/hr for nesiritide, with a full range of 0.6 to 6.4. These are descriptive summaries of the observed treatment periods. The ranges overlap, and their endpoints show that observed values varied within each treatment condition. A median and range alone do not establish whether the treatment-period values differed in a statistically reliable way.
The comparison is especially important to read in light of the crossover design. Each participant received both study drugs, so a natural treatment comparison would use each participant's response under nesiritide in relation to that same participant's response under placebo. The posted arm summaries do not show those paired differences. Without participant-level results or a reported paired analysis, the medians cannot reveal whether most participants had higher, lower, or similar urine output under one treatment.
No inferential analysis is posted for the primary outcome: the registry records 0 analyses. A confidence interval, p-value, or other estimate of uncertainty for the treatment contrast is not reported in the registry record. This absence means the precision of the difference between treatments cannot be assessed from these summaries alone. It does not establish that the treatments were equivalent, nor does it establish that a difference was absent.
The study is described as a pilot and enrolled 9 participants. This small enrollment makes the observed summaries particularly sensitive to individual measurements, while the full ranges convey some of the variability present in the data. The registry does not report a sample-size justification or identify a prespecified clinically important difference. The posted values therefore should be read as limited descriptive evidence, not as a definitive estimate of the treatment effect.
The record also lists safety and hemodynamic outcomes, but outcome names alone do not supply results. The posted adverse-event figures show no serious adverse events, other reported adverse events, or deaths in either treatment group. Those figures describe the recorded events within the study; the small enrollment and absence of a detailed safety analysis limit what can be concluded about uncommon events or broader safety patterns.
9. Statistical Methods Explained
The registry presents the primary outcome as a median with a full range. These are descriptive statistics: they summarize the observed measurements without, on their own, estimating how uncertain a treatment contrast is. A median is the central ordered observation, while the full range reports the lowest and highest observed measurements. The range is useful for seeing the span of observed values, but it does not indicate how densely observations lie near the median or whether any extreme value had a strong influence.
Why the crossover structure matters
In a crossover study, participants receive more than one treatment, usually in distinct periods. Here, random assignment determined whether nesiritide or placebo came first, and each participant was scheduled to receive both. A comparison can therefore use within-participant information, which may reduce the influence of stable differences among infants. This is a general advantage of crossover designs, not proof that such an analysis was used for these results.
For a crossover analysis, the observations from the same participant are related rather than independent. A suitable analysis generally accounts for that pairing. It may also consider period effects, because measurements can change over time for reasons unrelated to the assigned study drug, and carryover, if effects of the first period persist into the next one. A washout period is described, but its presence alone does not show that carryover was absent. The statistical model and any checks or adjustments for these issues are not reported in the registry record.
What the posted summaries can establish
The reported treatment medians describe the center of the observed urine-output values in each condition. The full ranges describe the extremes. They do not give a standard error, confidence interval, or p-value for the within-participant contrast. Nor do they show the distribution of paired differences. For example, the same treatment medians could arise from different participant-level patterns, so aggregate summaries do not reveal how consistently participants responded in one direction.
A confidence interval is a general statistical method for expressing uncertainty around an estimated quantity, such as a treatment contrast. Its width depends on the amount and variability of information and on the analysis model. No confidence interval for the primary treatment comparison is reported in the registry record. Consequently, the precision of that contrast cannot be read from the posted medians and ranges alone.
Why variability and distribution matter
Urine-output observations may vary substantially across participants. A median is less affected than a mean by a very extreme measurement, but it still does not explain the source of variation or the pattern of individual responses. The range shows the outermost values and can be wide even when most observations are relatively close together. Conversely, a narrower range does not by itself demonstrate a more precise treatment effect. Precision of the comparison depends on the paired differences and the analysis, not just on each treatment's separate range.
Over-dispersion is a general concept used when observed variation is greater than a statistical model expects. If a model assumes less variability than the data contain, its uncertainty estimates may be too small. The registry's summary statistics do not provide enough information to assess over-dispersion or to identify a fitted model. No model-based primary analysis is reported.
Planning illustrations are not trial results
Any sample-size planning illustrations associated with the posted results are hypothetical calculations, not observed findings and not evidence of the study's actual design rationale. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. These assumptions are described as an illustration computed from the observed effect, not as the trial's own design. Such calculations do not constitute observed power and cannot replace a confidence interval or a prespecified sample-size justification. The registry record does not report the trial's own sample-size justification.
For time-to-event outcomes, a planning calculation may count total events, whereas other planning calculations may express the required number as participants per arm. Those are planning conventions, not counts observed in this trial. The primary outcome is urine output, and the record does not report a time-to-event endpoint.
Analysis and reporting
The registry identifies four outcome measures and records 0 analyses. It provides descriptive primary results but no inferential comparison. The statistical method used to produce the reported medians and ranges beyond the stated summaries, the handling of missing observations, and any sensitivity analyses are not reported in the registry record. In the absence of those details, the posted results support a descriptive account of recorded urine output, but not a reconstruction of the full statistical analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, including the primary urine-output endpoint and three secondary outcomes. Considering several outcomes can raise the issue of multiplicity: when many statistical tests are conducted, the chance of at least one apparently notable result can increase. A prespecified hierarchy, adjustment procedure, or other strategy can help clarify how multiple outcomes are interpreted. The registry record does not report a multiplicity plan, and it records 0 analyses. No adjustment or testing strategy should therefore be inferred.
The secondary outcomes named in the record are the number of participants with hypotension and bradycardia, urine output, and cardiac index. Their names indicate what was intended for measurement, but do not provide numerical findings. Results for these measures are not reported in the registry record in the posted results. The registry also states that safety and pharmacokinetic data were study aims, but does not give a detailed analysis plan for those aims.
Information about missing outcome values, exclusions, withdrawals, or incomplete treatment periods is not reported in the registry record. The record does not specify an analysis population, such as whether analyses followed all randomized participants or included only participants with measurements in both periods. In a crossover study, those details matter because a participant may have data for one treatment period but not the other, and a paired comparison requires usable observations from both conditions.
The enrollment figure is 9, and the posted treatment summaries each list 9 participants. These counts do not, by themselves, describe data completeness for every outcome or explain how the analysis handled missing measurements. No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record. As a result, the impact of missing data on the primary and secondary outcome summaries cannot be assessed from the registry information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Nesiritide | 0 | 9 | 0.0% |
| Placebo | 0 | 9 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nesiritide | 0 of 9 |
| Placebo | 0 of 9 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Nesiritide | 0 of 9 |
| Placebo | 0 of 9 |
The posted adverse-event figures list 9 participants at risk in each treatment group. For nesiritide, 0 serious adverse events, 0 other adverse events, and 0 deaths are recorded. For placebo, the corresponding figures are also 0, 0, and 0. These are counts within the recorded study groups, not estimates of the rate of events beyond this trial.
The registry identifies hypotension and bradycardia as a secondary outcome, but the adverse-event counts alone do not supply a separate result for that named outcome. Whether those events were assessed under another definition or analysis is not reported in the registry record. The record also does not describe event severity criteria, observation duration for each event category, or the method used to collect adverse-event information.
Zero recorded events in a small pilot study do not establish that the risk of an event is zero. Such counts describe what was recorded among the participants in this study and cannot rule out uncommon events or events that were not captured or reported. The figures should be read narrowly as the posted counts, without extending them to a broader population or treating them as a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The posted result is a descriptive comparison of urine output under placebo and nesiritide in a randomized crossover pilot study after cardiopulmonary bypass in infants. It reports a median of 2.9 cc/kg/hr for placebo and 3.1 cc/kg/hr for nesiritide, with full ranges of 1.1 to 7.1 and 0.6 to 6.4, respectively. The record does not report an inferential test or an uncertainty interval for the treatment contrast.
These summaries do not show the participant-level paired differences that are central to a crossover comparison. They cannot establish whether urine output generally rose, fell, or remained similar for individual participants between the two treatment periods. Nor can the results establish equivalence or a clinically meaningful difference: no equivalence margin or clinically important threshold is reported in the registry record.
The findings also do not answer every aim named in the record. Safety and pharmacokinetic data are identified as aims, and hemodynamics are part of the study purpose, but the detailed results for these aims are not reported in the registry record in the posted outcome information. The named secondary outcomes should not be mistaken for results.
The study's pilot designation and enrollment of 9 participants place the descriptive findings in a limited evidential context. A small study can offer preliminary observations, but these data do not establish how findings would generalize to a broader group of infants or to different clinical circumstances. No medical conclusion should be drawn from the posted summaries alone.
In short, the registry records treatment-period urine-output summaries and no inferential analysis of their contrast. It also records zero adverse events in the listed categories for both groups. These statements describe the posted data; they do not establish absence of a treatment effect, prove treatments are equivalent, or resolve broader questions about efficacy or safety.
13. Why This Trial Matters Statistically
This study illustrates why trial design and summary statistics need to be read together. A crossover design exposes each participant to both study drugs, so the core comparison is naturally within participants. Separate medians and ranges are easy to interpret descriptively, but they do not display the paired treatment differences that would show how measurements changed within each infant.
It also demonstrates the distinction between a result and an analysis. The registry reports primary-outcome summaries, yet records 0 analyses. Without an inferential comparison, readers cannot determine the precision of a treatment contrast from a confidence interval or assess it using a reported test. A descriptive difference between medians is not itself a statistical test or evidence of a particular level of certainty.
The endpoint's summary form matters too. Medians and full ranges convey the center and extremes of the observed measurements, but not the distribution's shape or the relation between paired observations. That is a useful reminder that no single summary captures every aspect of a dataset. A complete account would also make the analysis population, missing-data handling, and crossover-specific modeling choices clear; those details are not reported in the registry record.
Finally, the pilot scale is relevant to how the evidence is framed. An enrollment of 9 can provide an account of the observations collected, while leaving substantial uncertainty about how broadly they apply. Planning illustrations based on an observed effect are not a substitute for the original design rationale or for an uncertainty estimate. The record does not report the trial's sample-size justification. This combination makes the study a useful example of why statistical interpretation should distinguish descriptive patterns, inferential evidence, and design limitations.
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 the small pilot enrollment of 9 participants. The registry's treatment summaries are descriptive and do not include a confidence interval or inferential analysis. In a crossover study, the absence of participant-level paired results is particularly limiting: separate medians and ranges do not reveal the distribution of within-participant differences or their precision.
The registry record does not report a detailed statistical analysis plan, a sample-size justification, or how period and potential carryover effects were handled. Although a two hour washout is specified in the treatment schedule, that fact alone does not demonstrate that carryover was absent. The methods used to analyze the crossover observations are not reported in the registry record.
Missing-data and analysis-population details are also unavailable. The record does not explain whether all randomized participants completed both periods, how incomplete observations were treated, or whether any participants were excluded from a particular outcome analysis. The posted counts do not resolve those questions for every endpoint.
The registry marks the study as terminated but does not report the reason for termination. It also lists secondary outcomes without posting detailed numerical results for them. Event definitions, ascertainment procedures, and follow-up details for safety outcomes are not reported in the registry record. Consequently, the posted zero event counts should be interpreted as recorded counts, not as a complete characterization of risk.
Finally, the record does not identify a clinically important threshold for urine output or an equivalence margin. Without those details and without an uncertainty estimate, the clinical importance of the numerical summaries cannot be determined from the registry results alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nesiritide Use Following Cardiac Surgery in Infants — NCT00281671.
- Registry record last updated 2020-08-27; status last verified 2018-05.
- Results first posted 2020-08-27.
- 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.
18. Record Summary
NCT00281671 is a randomized, quadruple-masked crossover pilot study of nesiritide and placebo following cardiopulmonary bypass in infants. The registry lists Phase 1 and Phase 2, enrollment of 9, and terminated status. Participants were scheduled to receive each infusion for 10 hours, separated by a two hour washout.
The primary outcome was urine output in cc/kg/hr during the last 5 hours of infusion, summarized by medians and full ranges. The posted summaries are 2.9, range 1.1 to 7.1, for placebo and 3.1, range 0.6 to 6.4, for nesiritide. The record lists 0 analyses and does not report an inferential comparison or confidence interval.
Three secondary outcomes are named, but detailed results are not reported in the registry record. The posted adverse-event figures record 0 serious adverse events, 0 other adverse events, and 0 deaths in each treatment group. The record does not report a sample-size justification, missing-data methods, or the detailed statistical handling of the crossover design.