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 Study Comparing Bivalirudin Versus Heparin in Neonatal and Pediatric ECMO (NCT03318393), a randomized phase 4 study. The primary outcome is Percentage of Time Spent at Goal Anticoagulation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03318393 |
| Phase | Phase 4 |
| Condition | Extracorporeal Membrane Oxygenation Complication, Pediatric ALL, Anticoagulants |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Texas Southwestern Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns neonatal and pediatric patients receiving extracorporeal membrane oxygenation (ECMO). The brief summary describes enrollment at a single pediatric Level 1 trauma center. The registry lists an enrollment of 30, and the primary outcome is recorded for 14 participants in the unfractionated heparin group and 16 in the bivalirudin group. The record does not report further eligibility details or characteristics of the enrolled patients.
Intervention
The intervention is anticoagulation with bivalirudin. Participants randomized to this group are described as receiving anticoagulation with bivalirudin. The registry does not report additional details about how the treatment was managed or adjusted.
Comparator
The comparator is unfractionated heparin, described as the usual-care primary anticoagulant for participants assigned to that arm. The study is randomized and parallel, with no masking reported. Further details about treatment protocols are not reported in the registry record.
Primary question
The primary question is whether the groups differ in the percentage of time spent at goal anticoagulation through study completion, described as an average of 1-2 weeks. The posted primary outcome is summarized by a median and inter-quartile range for each group. The registry does not report a primary-outcome statistical comparison, a confidence interval for the between-group difference, or a p-value. The posted summaries therefore describe each group but do not establish the precision of a comparative effect estimate.
3. Trial Design
This is a prospective randomized pilot study comparing bivalirudin with unfractionated heparin in neonatal and pediatric patients receiving ECMO. The registry classifies the allocation as randomized, the model as parallel, and masking as none. It lists the phase as Phase 4 and the study status as completed. The brief summary describes a single pediatric Level 1 trauma center.
The registry lists enrollment of 30 and describes an intended allocation of 15 patients to each arm. The posted primary outcome records 14 participants in the unfractionated heparin group and 16 in the bivalirudin group. The reason these outcome group sizes differ from the intended allocation is not reported in the registry record. The record does not report whether participants who were randomized but did not contribute primary outcome data were excluded, or why that might have occurred.
The study start is recorded as 2018-03-25, and primary completion as 2021-10-08. Both interventions are listed as drugs. The primary aim is described as comparing the efficacy of bivalirudin with unfractionated heparin, using time at goal anticoagulation as the primary outcome. A secondary outcome is the number of participants with one or more major bleeding events. The registry lists three outcome measures but posts one secondary outcome. Detailed eligibility criteria, treatment administration procedures, the randomization process, and the statistical analysis plan are 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
| Stage | Unfractionated Heparin Group | Bivalirudin Group |
|---|---|---|
| STARTED | 14 | 16 |
| COMPLETED | 14 | 16 |
| 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 | Unfractionated Heparin Group | Bivalirudin Group | Total |
|---|---|---|---|---|
| Participants analysed | 14 | 16 | 30 | |
| Age, Categorical: <=18 years | Participants | 14 | 16 | 30 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 7 | 11 | 18 |
| Sex: Female, Male: Male | Participants | 7 | 5 | 12 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 14 | 16 | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Time Spent at Goal Anticoagulation, measured over through study completion, an average of 1-2 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | percentage of time |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of time spent at goal anticoagulation through study completion, described as an average of 1-2 weeks. It is summarized with a median and inter-quartile range for each treatment group. The median represents the central value in the observed distribution, while the inter-quartile range describes the middle portion of that distribution. These summaries offer information about typical time at goal and variation across participants without assuming that the outcome follows a symmetric distribution.
In general, time at a target level can reflect how consistently anticoagulation remains within a clinically specified range during treatment. That makes it a measure of control over time rather than a single measurement at one moment. The target definition, measurement frequency, handling of missing measurements, and specific calculation of time at goal are not reported in the registry record, so the operational details behind the endpoint cannot be assessed from the posted information.
The registry records a median of 0.63, with an inter-quartile range from 0.5 to 0.82, for unfractionated heparin, and a median of 0.49, with an inter-quartile range from 0.31 to 0.54, for bivalirudin. The unit is described as percentage of time, but these posted values are retained as recorded and are not converted to another scale. The summaries are group-specific; the registry does not report a formal comparison of the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is descriptive. The median time-at-goal value is 0.63 in the unfractionated heparin group and 0.49 in the bivalirudin group. The corresponding inter-quartile ranges are 0.5 to 0.82 and 0.31 to 0.54. These values show the distributions reported for each group, but they are not themselves an estimate of the uncertainty around a between-group effect.
The registry does not report a primary-outcome comparison, confidence interval, or p-value. Consequently, the posted primary summaries do not indicate how precisely the groups differ, nor do they establish whether any observed contrast is compatible with chance variation. The overlap and separation of group summaries should not be treated as a substitute for an analysis that directly estimates the comparative effect. The analysis method for the primary outcome is not reported in the registry record.
The outcome group sizes are 14 and 16. These are the numbers contributing to the posted primary outcome and are different from the intended allocation described in the study summary. The reason is not reported. Without information about outcome availability and the analysis population, the extent to which the reported summaries represent all randomized participants cannot be determined from the record.
For the secondary major-bleeding outcome, the registry records 7 participants with one or more events in each group. A recalculated unadjusted comparison reports p = 0.732. In general, a p-value describes how compatible observed data are with a specified null model; it is not the probability that a treatment effect is absent. The recalculated result is not evidence that the groups are equivalent, and the registry does not post a sponsor-reported analysis for this outcome. The comparison is also imprecise, as reflected by the wide interval reported for the recalculated risk difference.
These results must be read in the context of a pilot study with randomized treatment assignment but no masking. Randomization can help balance groups on average, but small group sizes can leave substantial uncertainty and chance imbalance. The registry record does not report adjusted analyses or details that would establish how outcomes were handled in participants with incomplete data. The posted summaries support a description of the recorded outcomes; they do not justify a broad claim about comparative clinical effectiveness or safety.
9. Statistical Methods Explained
Statistical summaries and comparative estimates answer different questions. A median and inter-quartile range describe the observed outcome within each group. A treatment comparison instead estimates how far apart the groups are and how uncertain that estimate is. The primary endpoint is reported using the first type of summary only. No primary comparative estimate or inferential result is reported in the registry record.
What does a confidence interval communicate?
In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. A narrow interval indicates greater precision than a wide interval, all else being equal. An interval that includes no difference does not prove that the groups are the same; it indicates that the data and method do not rule out no difference at the stated confidence level. The registry does not provide a confidence interval for the primary outcome.
For the secondary major-bleeding outcome, the posted event counts are 7 of 14 in the unfractionated heparin group and 7 of 16 in the bivalirudin group. The recalculated unadjusted risk-difference interval is wide, extending from -0.420 to 0.295. This indicates substantial uncertainty around the estimated difference. In general, a risk difference expresses the difference between the event risks in two groups; a value below zero in the stated comparison direction favors a lower observed risk in the bivalirudin group. The interval crosses zero, so the recalculated result does not exclude no difference under its method.
How should the p-value be read?
The recalculated unadjusted p-value for this secondary comparison is 0.732. In general, a p-value measures how unusual data at least as discordant with a null hypothesis would be if that hypothesis and the test assumptions were correct. It does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. A relatively large p-value cannot establish equivalence or rule out meaningful differences, especially when the estimate is imprecise.
The recalculated risk difference, risk ratio, odds ratio, and p-value are unadjusted re-calculations from the posted summary counts. They are not reported sponsor analyses. The registry lists no reported analyses for the secondary endpoint. The statistical method used by the investigators, including any covariate adjustment or alternative analysis, is not reported in the registry record. The registry record does not flag a discrepancy between the posted values and these recalculations.
Why does the planning illustration not measure trial power?
The planning illustration is based on the observed effect and is not the trial's own design justification. It uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Such calculations can illustrate the scale of a future study under those assumptions. They do not show the probability that this completed trial would detect an effect, and they do not establish that the observed effect is stable. The trial's sample-size justification and design assumptions are not reported in the registry record.
In general, power is the probability that a prespecified analysis will detect an effect of a specified size under specified assumptions. It depends on the design, outcome variability, allocation, analysis method, and chosen threshold. A retrospective illustration based on the observed estimate is not observed power: it uses an effect estimated from the same small study, which can be unstable. The planning calculations therefore should be interpreted as conditional illustrations rather than as a statement about the trial's ability to answer its primary question.
What is not available for the primary analysis?
The primary outcome is reported as medians and inter-quartile ranges, but the registry does not report a test or model for comparing these distributions. It does not report a primary confidence interval, p-value, covariate adjustment, or missing-data method. The specific target range for anticoagulation and the way repeated measurements were combined into time at goal are also not reported in the registry record. Without these details, readers cannot reproduce or fully evaluate the primary analysis from the posted record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and posts one secondary outcome in addition to the primary outcome. It does not report a multiplicity adjustment or explain how the analysis handled the possibility of testing more than one outcome. The statistical analysis plan, including any prespecified hierarchy or distinction between confirmatory and exploratory analyses, is not reported in the registry record. Without those details, the role of the posted secondary result in the planned inferential framework is unclear.
The registry indicates zero reported analyses for the secondary outcome. That is distinct from saying that no analyses were conducted; it means no analysis is posted in the record. The recalculated unadjusted comparison is a separate calculation from the posted summary counts, not a sponsor-reported analysis. No primary-outcome inferential analysis is reported either.
Missing-data methods and analysis populations are not reported in the registry record. The primary outcome summaries use 14 participants in the unfractionated heparin group and 16 in the bivalirudin group, while the study summary describes intended allocation of 15 participants per group. The record does not explain the difference or state whether the primary outcome was analyzed by intention to treat, per protocol, or another population definition. It also does not report missing observations, exclusions, or how incomplete measurement periods were handled.
In general, incomplete data can affect both the amount of information available and the interpretation of a treatment comparison. The effect depends on why data are missing and how the analysis handles them. Since the registry does not report those details, the impact of any missing outcomes cannot be evaluated. These omissions limit assessment of both multiplicity and the robustness of the reported summaries; they do not by themselves establish that the analyses were biased.
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 |
|---|---|---|---|
| Unfractionated Heparin Group | 7 | 14 | 50.0% |
| Bivalirudin Group | 7 | 16 | 43.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Unfractionated Heparin Group | 2 of 14 |
| Bivalirudin Group | 3 of 16 |
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 |
|---|---|
| Unfractionated Heparin Group | 0 of 14 |
| Bivalirudin Group | 0 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | Unfractionated Heparin Group | Bivalirudin Group |
|---|---|---|---|
| Major bleeding event | Blood and lymphatic system disorders | 7 of 14 | 7 of 16 |
Serious events with the highest arm-level rate: major bleeding event (50.0%).
The registry records 7 participants with one or more major bleeding events in the unfractionated heparin group and 7 in the bivalirudin group. The corresponding group sizes for this outcome are 14 and 16. These are observed counts, not adjusted comparisons. The recalculated unadjusted comparison has p = 0.732, but the event information is too imprecise to establish that the groups have similar risks or that one group has a lower risk.
The record also lists zero other adverse events in each group and deaths of 2 in the unfractionated heparin group and 3 in the bivalirudin group. The definition and attribution of the death counts are not reported in the registry record, so they should not be interpreted as treatment-related deaths. The serious adverse event term listed as the leading term is major bleeding event, with 50.0% recorded. The record does not provide further detail that would clarify the denominator or calculation behind that percentage.
In general, safety counts from a small study are descriptive and may be highly uncertain. They do not establish comparative safety, particularly when event definitions, follow-up, attribution, and analysis methods are not fully reported. These figures should be read as the events recorded in the registry, not as a complete assessment of risk.
12. What the Result Does, and Does Not, Mean
The registry record supports a limited description of outcomes in a randomized pilot study. It reports median time at goal anticoagulation of 0.63 for unfractionated heparin and 0.49 for bivalirudin, with the stated inter-quartile ranges. It also records the major-bleeding event counts and other safety information. The groups were assigned through randomization, but masking is listed as none.
The primary summaries do not establish the size or precision of a between-group effect because the registry does not report a primary comparison. The secondary unadjusted recalculation is imprecise and cannot establish either equivalence or a meaningful difference. A non-significant p-value is not proof that treatments have the same effect. Likewise, a difference between descriptive medians is not, by itself, proof of a treatment effect.
The record does not provide enough information to assess the full analysis process. The primary outcome measurement details, missing-data methods, analysis populations, multiplicity approach, and statistical plan are not reported in the registry record. Those gaps matter when interpreting what the group summaries represent and how much confidence to place in comparative conclusions.
The study is identified as a pilot and has posted outcomes from groups of 14 and 16 participants. Its results may help describe what was recorded in this study and illustrate questions for further research, but the registry information does not support generalizing an effect beyond the studied population and setting. These findings are not a basis for treatment recommendations. They are evidence about the posted trial record, with substantial uncertainty around comparative interpretation.
13. Why This Trial Matters Statistically
This trial is statistically informative because it illustrates the difference between a randomized design and a conclusive comparative result. Randomization is a design feature intended to support fair comparison, but it does not guarantee precise estimates, particularly in a pilot study with the posted group sizes. The primary endpoint is described using within-group medians and inter-quartile ranges, yet no primary comparative estimate is reported. A reader therefore has descriptive outcome summaries without the uncertainty measure needed to quantify a primary contrast.
The secondary event counts also demonstrate why counts and p-values should be interpreted together with uncertainty. The recalculated unadjusted comparison yields a broad interval and p = 0.732. That combination does not establish no difference; it signals that the observed data leave considerable uncertainty. In general, a failure to reject a null hypothesis is not the same as evidence of equivalence, which requires an appropriate design and analysis.
The record also highlights the importance of complete reporting. The intended arm allocation differs from the group sizes contributing primary results, but the reason is not reported. Analysis populations, missing-data procedures, multiplicity handling, and the primary statistical method are also not reported in the registry record. These details affect how clinicians and researchers should interpret even clearly presented summary statistics.
Finally, the planning illustration is based on the observed effect rather than the study's own design. This distinction matters because planning calculations are conditional on assumptions and cannot retroactively demonstrate that a completed study had adequate power. Together, these features make the trial a useful example of why statistical interpretation depends not only on point estimates, but also on design, precision, and transparent analysis reporting.
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.
Several limitations specific to this trial constrain interpretation of the posted results. The study is described as a pilot, is open-label, and was conducted at a single pediatric Level 1 trauma center. The record does not report the randomization procedure or measures used to reduce bias in outcome assessment. Lack of masking may matter for outcomes involving clinical judgment or measurement decisions, although the extent of any effect cannot be determined from the registry record.
The primary endpoint is given as group medians and inter-quartile ranges without a between-group estimate, confidence interval, or p-value. Its operational definition is not described beyond the percentage of time spent at goal anticoagulation and the timeframe. The target range, measurement schedule, calculation rules, and handling of incomplete monitoring are not reported. This limits reproducibility and makes it difficult to assess whether the group summaries are directly comparable.
Primary outcome group sizes are 14 and 16, whereas the study summary describes 15 participants in each planned arm. The reason is not reported. The record also does not identify the analysis population or explain any exclusions or unavailable outcomes. The impact of the group-size difference and any missing data therefore cannot be assessed.
For safety, event counts are sparse and the registry provides limited information on event definitions, attribution, and follow-up. The secondary comparative statistics are recalculated and unadjusted rather than posted sponsor analyses. The study's sample-size justification, statistical analysis plan, and multiplicity approach are not reported in the registry record. These limitations mean the available record is best read as a partial account of a small randomized study, not a complete basis for definitive comparative claims.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Comparing Bivalirudin Versus Heparin in Neonatal and Pediatric ECMO — NCT03318393.
- Registry record last updated 2023-01-31; status last verified 2022-12.
- Results first posted 2023-01-31.
- 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.
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18. Record Summary
The registry record describes NCT03318393, a prospective randomized pilot study of bivalirudin versus unfractionated heparin for neonatal and pediatric ECMO. It is listed as Phase 4, parallel, unmasked, and completed. Enrollment is recorded as 30, with the brief summary describing intended allocation of 15 participants to each group at a single pediatric Level 1 trauma center.
The primary outcome is percentage of time at goal anticoagulation through study completion, described as an average of 1-2 weeks. Group medians and inter-quartile ranges are posted, but no primary comparative analysis is reported. The secondary outcome is the number of participants with one or more major bleeding events. The record also lists adverse-event counts and deaths. A recalculated unadjusted secondary comparison is available, but no sponsor-reported analysis is posted.
The study start is recorded as 2018-03-25 and primary completion as 2021-10-08. The registry does not report the statistical plan, primary analysis method, missing-data handling, or multiplicity approach. The posted information is therefore descriptive and limited in its ability to support precise comparative conclusions.