Cord Blood Transfusion In Preterm Neonates (CB-TrIP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cord Blood Transfusion In Preterm Neonates (CB-TrIP) (NCT03764813), a registered phase not stated study. The primary outcome is Median Percentage of HbF at 32 Weeks of Post Menstrual Age.

2. Clinical Question

The study rationale centers on the different oxygen affinities of fetal hemoglobin (HbF) and adult hemoglobin (HbA). The investigators hypothesized that using cord-blood RBC, described as containing almost exclusively HbF, might prevent a non-physiological decrease in HbF in preterm neonates. That proposed mechanism and potential protection from oxygen radical diseases are hypotheses in the registry summary, not findings established by the posted results.

The study aimed to monitor HbF in preterm neonates receiving RBC transfusions from cord blood, adult donors, or both. It is described as monocentric, prospective, and nonrandomized. Because allocation is not stated and the exposure groups were not formed through a reported randomized comparison, differences between groups could reflect factors other than transfusion source. The registry record does not report a primary-endpoint result with which to assess the stated question.

3. Trial Design

CB-TrIP is described in the registry record as a monocentric, prospective, nonrandomized study. Its stated aim was to monitor HbF levels in preterm neonates receiving red blood cell transfusions from umbilical blood donated by healthy full-term babies (CB-RBC), adult donors (A-RBC), or both. The record also lists a non-transfused group in its adverse-event information. Allocation is not stated; the record therefore does not establish how neonates entered these exposure groups.

The registry lists an enrollment of 25. This is the recorded enrollment, not a statement about how many contributed to every analysis. The primary endpoint description says that 264 HbF results were included in the analysis. Those are repeated measurements, not a count that can be interpreted as the number of participants. The record does not report how many participants contributed HbF results or how those results were distributed across participants and exposure groups.

The study status is COMPLETED. The recorded start date is 2018-12-05 and the primary completion date is 2019-08-02. The primary outcome is the median percentage of HbF at 32 weeks of postmenstrual age, measured from study entry through completion of postmenstrual age of 32 weeks. Listed secondary outcomes are post-transfusion hematocrit change, intervals between transfusions, and median percentage of HbF at the last assessment.

Because the study was not randomized and allocation is not stated, its exposure groups should not be read as equivalent treatment arms. The registry specifically cautions that the arms are not a like-for-like control comparison. The record does not report a protocol, a statistical analysis plan, or a sample-size justification. Planning illustrations based on the observed effect are not the trial's own design justification and do not establish the study's observed statistical power.

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: Among 29 couples, 25 accepted to participate and overall 25 patients were enrolled.

From Enrollment to the Age of 32 Weeks

Reasons for not completing this period:

From Enrollment to the Last HbF Test

Analysis population for the primary outcome, as defined in the registry: The overall amount of 264 HbF results were included in the analysis. HbF was expressed as percentage of total Hb (i.e. HbF+HbA1+HbA2)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: These data refer to all patients enrolled in the study, grouped according types of transfusions received (if any) until the completion of the age of 36 weeks, discharge or death.

6. Primary Endpoint

The registry lists the primary outcome as Median Percentage of HbF at 32 Weeks of Post Menstrual Age, measured over From study entry to the completion of postmenstrual age of 32 weeks.

The primary endpoint is the median percentage of HbF at 32 weeks of postmenstrual age. HbF is expressed as a percentage of total hemoglobin, defined as the sum of HbF, HbA1, and HbA2. The registry says HbF was determined by high-performance liquid chromatography and gives the calculation as HbF divided by the sum of HbA1, HbA2, and HbF.

A median describes the central position of observed values while being less influenced by unusually high or low measurements than a mean. The inter-quartile range (IQR), specified as the dispersion measure, describes the spread of the middle portion of those measurements. These summaries can describe the distribution of HbF percentages at the specified endpoint, but they do not by themselves show how HbF changed over time or establish why it changed.

The endpoint is relevant to the study's stated question because the investigators hypothesized that transfusion source might affect HbF levels in preterm neonates. A measurement at 32 weeks of postmenstrual age provides a specified time point for describing HbF. The record states that 264 HbF results were included in the analysis, but does not report the median, IQR, or a group-specific endpoint result. It also does not report how repeated measurements were handled in the analysis leading to the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is described with a median and an inter-quartile range. In general, the median is a measure of the center of a distribution that is relatively resistant to extreme observations. The IQR describes variability in the central part of the distribution. Reporting both can be useful when values are skewed or when a small number of observations are unusually high or low. The registry record does not report the actual median or IQR for the primary endpoint, so their values and the observed spread cannot be assessed.

What does the endpoint measure?

The endpoint is the median percentage of HbF at 32 weeks of postmenstrual age. The measure is defined relative to total hemoglobin, with total Hb stated as HbF plus HbA1 plus HbA2. The registry describes high-performance liquid chromatography as the method used to determine HbF. This makes the endpoint a laboratory measurement of the composition of hemoglobin, rather than a direct measure of clinical disease or a clinical outcome.

The time frame is from study entry to completion of postmenstrual age of 32 weeks. A specified time point helps define which measurements are relevant to the primary question. However, the record does not describe how values were selected if multiple results were available near that time point, nor does it say how missing measurements were handled. Those details are not reported in the registry record.

Why do repeated measurements matter?

The primary outcome description says that 264 HbF results were included. Because the study monitored HbF levels over time, results may include repeated measurements from the same neonate. General statistical practice must account for the fact that measurements from the same person tend to be more alike than measurements from different people. If such correlation is ignored, the analysis may give too much weight to participants with more measurements and may overstate precision. The registry does not report the statistical method used to account for repeated measurements, or whether the primary endpoint was calculated from participant-level summaries or from the full set of results.

This distinction also explains why the number of HbF results cannot be treated as the number of participants. The registry reports enrollment of 25 and separately reports 264 HbF results included in the analysis. It does not state how many participants contributed those results or how many observations each participant contributed. The measurement count alone cannot establish the effective amount of independent information available for an analysis.

What can a confidence interval tell the reader?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval around a median or a group difference would help readers judge which values are compatible with the data and method. The registry record does not report a confidence interval for the primary endpoint or a comparison between exposure groups. No interval or precision claim can therefore be made from the posted results.

How should planning illustrations be understood?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the illustration uses total events under the Schoenfeld approach; other illustrations express participants per arm. These are planning assumptions, not evidence that the trial was designed with those assumptions, and not a measure of observed power.

A sample-size calculation is generally used to explore how much information a future study might need for a specified target effect and statistical assumptions. When the target is derived from an observed effect, the illustration depends on that estimate and may not represent a clinically meaningful target. It should not be read as a retrospective verdict on whether the completed study was adequately powered. The record does not report the trial's own sample-size justification or design assumptions. No planning-illustration values are stated in the registry record.

Why is a nonrandomized comparison difficult to interpret?

Random allocation can, on average, balance both measured and unmeasured participant characteristics across groups. This study is described as nonrandomized, and allocation is not stated. The listed exposure groups therefore cannot be assumed to have comparable starting characteristics. For example, clinical circumstances associated with receiving a particular transfusion source could also be associated with HbF measurements or adverse events. This is a general concern about nonrandomized comparisons, not a claim that any particular imbalance occurred in this study.

Statistical adjustment can sometimes address differences in measured characteristics, but it cannot guarantee removal of confounding, especially when important factors were not measured or were not included in the model. The registry record does not report a comparative analysis plan, adjustment variables, or adjusted estimates. The record also explicitly cautions that the groups are not a like-for-like control comparison. As a result, descriptive group figures should not be interpreted as causal effects.

What role does over-dispersion play?

In general, over-dispersion occurs when count outcomes vary more than a chosen statistical model expects. If it is present and ignored, standard errors can be too small and confidence intervals too narrow. This matters for event counts or other outcomes whose variability exceeds the model's assumptions. The registry record does not report an over-dispersion assessment or a count model for the listed outcomes, so it is not possible to say whether over-dispersion arose or how it was handled.

Overall, the methods information in the record identifies the endpoint, measurement method, summary statistics, and some planning assumptions. It does not specify the analysis model, uncertainty estimates, handling of repeated measurements, or approach to confounding. These omissions limit how far statistical interpretation can go beyond describing the stated study design and outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and four analyses. The primary outcome is the median percentage of HbF at 32 weeks of postmenstrual age. The listed secondary outcomes are post-transfusion hematocrit change, intervals between transfusions, and median percentage of HbF at the last assessment. The record does not describe how many hypotheses were tested, which analyses were confirmatory, or whether any multiplicity adjustment was planned or applied. It does not report a statistical analysis plan. Without that information, the risk of false-positive findings across multiple analyses cannot be assessed.

Multiplicity is a general concern when several outcomes, time points, or comparisons are tested. Each additional test can create another opportunity to observe a seemingly notable result by chance. Methods for addressing this can include specifying a primary hypothesis in advance, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry identifies a primary outcome but does not report the approach used to control or interpret multiplicity.

The primary endpoint description states that 264 HbF results were included. The record does not report how missing HbF observations were handled, whether participants without a measurement at the endpoint were excluded, or why data might be missing. Missingness can affect interpretation if the likelihood of having an observed measurement is related to participant condition or exposure. No assumptions or sensitivity analyses for missing data are reported in the registry record.

The record also does not define analysis populations for the primary or secondary outcomes, or provide participant flow for those analyses. Enrollment is listed as 25, but this does not establish the number contributing to any particular outcome. The record does not report whether analyses used all enrolled participants, only those with available measurements, or another specified population.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: retinopathy stage ii-iii (80.0%), documented infections (60.0%), necrotizing enterocolitis (60.0%).

The adverse-event record gives group-specific numbers at risk and numbers affected by serious adverse events, along with deaths. For non-transfused neonates, the record lists 13 at risk, 1 affected by a serious adverse event, and 0 deaths. For the group labeled Only Cord-TBC, it lists 3 at risk, 3 affected, and 1 death. For Only Adult-RBC, it lists 4 at risk, 3 affected, and 1 death. For Both Cord- and Adult-RBC, it lists 5 at risk, 5 affected, and 0 deaths.

The record lists 0 affected by other adverse events in each of the four groups. It also names Retinopathy stage II-III at 80.0%, documented infections at 60.0%, and Necrotizing enterocolitis at 60.0% among the top serious-event terms. The registry record does not provide enough context to identify the denominators for these percentages or whether an individual could contribute to more than one term.

These are descriptive safety figures, not randomized comparative estimates. Allocation is not stated, and the record warns that the groups are not a like-for-like control comparison. The adverse-event entries alone cannot establish that a transfusion source caused or prevented an event. The record does not report further detail about event timing, severity criteria, follow-up, or statistical comparisons.

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

The registry record documents a prospective study of HbF monitoring in preterm neonates and specifies a primary endpoint: median percentage of HbF at 32 weeks of postmenstrual age. It also states the measurement method and that 264 HbF results were included. These details make the study question and measurement definition clear. They do not provide the primary endpoint result itself. The median and IQR are not reported in the registry record, nor are comparative estimates for cord-blood and adult-donor transfusion groups.

The absence of reported endpoint results means the posted record cannot show the observed HbF level at the specified time point or the precision of that estimate. It also cannot establish whether HbF differed by transfusion source, whether any difference was clinically important, or whether the proposed mechanism was supported. The investigators' expectation that cord-blood RBC might prevent a decrease in HbF remains a stated hypothesis, not a conclusion demonstrated by the information in the record.

The nonrandomized design further limits causal interpretation. Allocation is not stated, and the registry cautions that the groups are not a like-for-like control comparison. Even reported group differences could reflect baseline differences, clinical decisions, or other factors rather than the transfusion source itself. The record does not report adjustment methods or analyses that would help address these issues.

The adverse-event figures describe counts in the listed groups, but are not enough to establish relative safety. Group composition, exposure, and follow-up may differ, and the serious-event term percentages lack denominator context in the record. These figures should be read as reported observations, not as evidence that one approach is safer or more harmful.

In general, a statistical result describes data in the context of an analysis method; it does not automatically establish a biological mechanism or a causal effect. Here, the registry record provides the study framework and selected safety counts, but not the primary numerical result, its uncertainty, or sufficient analysis detail for a comparative conclusion. The findings that can be stated should therefore remain limited to the design, measurement definitions, and counts actually reported.

13. Why This Trial Matters Statistically

This study illustrates why the unit of analysis matters in clinical research. Enrollment is listed as 25, while the primary outcome description reports 264 HbF results included in the analysis. Those quantities describe different things: enrolled participants and laboratory measurements. Repeated observations can offer information about patterns over time, but they are correlated within a participant and cannot simply be treated as independent people. Clear reporting of the statistical handling of repeated measures is important for judging the precision of findings.

The study also highlights the interpretive limits of nonrandomized exposure groups. The registry describes cord-blood and adult-donor RBC exposure, including participants exposed to both, as well as a non-transfused group. It states that allocation is not reported and that the arms are not a like-for-like control comparison. This makes it important to distinguish descriptive observations from estimates of causal effects.

Outcome definition and timing are also central. The primary endpoint specifies a median HbF percentage at 32 weeks of postmenstrual age, with a laboratory method and denominator defined. That level of definition helps readers understand what was intended to be measured. However, a well-defined endpoint is not enough to evaluate results: the estimate, its uncertainty, analysis population, and handling of missing and repeated observations are also needed.

Finally, planning calculations should be kept distinct from observed evidence. The registry describes planning illustrations based on an observed effect and specified assumptions, but does not report a trial-specific sample-size justification. Such illustrations can inform future planning; they are not observed power and do not replace reporting the outcome estimate and its uncertainty. Together, these features make the record a useful example of how design, measurement, analysis, and transparent results reporting all shape statistical interpretation.

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 registry record does not report the primary endpoint result, including the median percentage of HbF at 32 weeks of postmenstrual age or its IQR. It also does not report a comparative effect estimate, confidence interval, or statistical test for the primary endpoint. This prevents assessment of the observed result and its precision.

The study is described as monocentric and nonrandomized. Allocation is not stated, and the registry cautions that the groups are not a like-for-like control comparison. The record does not report baseline characteristics, adjustment variables, or an analysis addressing potential confounding. It therefore does not support causal attribution of group differences to transfusion source.

The primary outcome description reports 264 HbF results, but the record does not state how many participants contributed those results, how measurements were distributed across participants, or how within-participant correlation was handled. It also does not report how measurements at the endpoint were selected or how missing HbF values were treated. The number enrolled does not resolve these analysis-population questions.

The registry lists four outcomes and four analyses, but does not report a statistical analysis plan, multiplicity strategy, or which secondary analyses were intended to be confirmatory. Outcome-specific denominators and participant flow are not reported. The adverse-event term percentages are listed without denominator context, and further details about event timing and follow-up are not reported in the registry record.

The record does not report the trial's own sample-size justification. The stated planning illustrations are not substitutes for that information or for observed endpoint estimates. These limitations are specific to what the registry record reports; they do not establish that unreported analyses or information were absent from other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cord Blood Transfusion In Preterm Neonates (CB-TrIP) — NCT03764813.
• Registry record last updated 2021-08-17; status last verified 2021-08.
• Results first posted 2020-04-24.
• 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.

18. Record Summary

CB-TrIP (NCT03764813), titled Cord Blood Transfusion In Preterm Neonates, is listed as COMPLETED. The registry record lists Fondazione Policlinico Universitario Agostino Gemelli IRCCS as sponsor, enrollment of 25, a start date of 2018-12-05, and primary completion on 2019-08-02.

The study is described as a monocentric prospective nonrandomized study monitoring HbF in preterm neonates receiving cord-blood and/or adult-donor RBC transfusions. The primary endpoint is the median percentage of HbF at 32 weeks of postmenstrual age, measured by high-performance liquid chromatography. The primary outcome description states that 264 HbF results were included. The endpoint result and its IQR are not reported in the registry record.

Listed secondary outcomes are post-transfusion hematocrit change, intervals between transfusions, and median percentage of HbF at the last assessment. The registry reports adverse-event counts for non-transfused, cord-TBC, adult-RBC, and combined-exposure groups. It cautions that allocation is not stated and the groups are not a like-for-like control comparison.