Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery (NCT01330433), a randomized phase 2 study. The primary outcome is Severity of Adhesions at the Retrosternal Site.

2. Clinical Question

The clinical question is about a surgical sealant used during staged pediatric heart surgery, with adhesions as the named primary outcome and postoperative drainage as an additional concern. The planned adhesion assessment occurs at a later operation, rather than immediately after the first procedure. The registry record describes the evaluation as prospective, randomized, open-label, and blinded-evaluator. It also lists single masking, without identifying who was masked. Those descriptions do not establish from the record which participants or clinicians knew the assigned treatment, or which evaluator was masked.

The record identifies hospital stay as a secondary outcome and states that the trial evaluated bleeding through postoperative surgical-site drainage output. It does not provide numerical results for those outcomes in the registry record for this analysis. The question can therefore be described in terms of the planned comparison and measurement, but not answered with an estimate of the treatment difference.

3. Trial Design

The registry identifies this as a Phase 2, randomized, parallel-group study with enrollment of 35. The study status is completed. The recorded start is 2011-08, and primary completion is recorded as 2015-08. Loma Linda University is listed as the sponsor.

The comparison is between CoSeal Surgical Spray and no CoSeal Surgical Spray. The experimental group description says the spray was applied at the end of the first staged procedure; the comparator description says it was not applied at that point. Random assignment is specified, but the registry record does not report the allocation sequence method, concealment procedures, or whether assignment was stratified.

The study summary describes a prospective, randomized, open-label, blinded-evaluator design. The separate masking entry says single masking. The record does not identify the masked role or explain how these descriptions relate, so the exact masking arrangements are not reported in the registry record. The parallel design indicates that the assigned groups are compared rather than describing a crossover, but further details of follow-up and treatment adherence are not reported in the registry record.

The trial addresses children undergoing staged surgical reconstruction. The summary lists potential procedures including the Blalock-Taussig Type Operation, Classical Glenn Procedure, Bidirectional Glenn Procedure, and Norwood. It does not provide the number of participants undergoing each procedure, nor does it describe the distribution of clinical characteristics between the groups.

Adhesion severity was to be collected during approximately the first 30-60 minutes of the second staged surgery. The record also describes postoperative surgical-site drainage output as the measure used to evaluate bleeding, and lists hospital stay as a secondary outcome. Although the registry lists 8 outcome measures, it records 0 analyses. A statistical analysis plan, including the specific comparison method and handling of covariates, is 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:

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 Severity of Adhesions at the Retrosternal Site, measured over Severity of adhesions data will be collected during approximately the first 30-60 minutes of the second staged surgery.

The primary endpoint is titled “Severity of Adhesions at the Retrosternal Site.” Adhesions are abnormal bands of tissue that can form after surgery. The registry describes grading adhesion severity at seven predefined sites, including pericardial or retrosternal, inferior or diaphragmatic, right lateral or arterial, and regions around the great vessels. The grades distinguish no adhesions from adhesions requiring progressively more extensive dissection: 0 means no adhesions, 1 means filmy and avascular, 2 means requiring blunt dissection, 3 means requiring sharp dissection, and 4 means requiring extensive sharp dissection.

The record says that each patient’s adhesion score is derived by summing the site-specific grades, with a possible score from 0 (no adhesions) to 28 (cohesive adhesions at all sites). The assessment is scheduled during approximately the first 30-60 minutes of the second staged surgery. This timing allows the planned evaluation to take place when the operative field is available for direct assessment, rather than relying on an unobserved later outcome.

There is an important difference between the endpoint title and its description: the title names the retrosternal site, while the description explains a score formed from multiple sites. The registry also gives the unit as percentage of participants and the parameter as NUMBER, but does not state a threshold that would define which participants count as having an event. The record therefore does not clarify how the multi-site score corresponds to a percentage-based endpoint. A single summary comparison is not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended to make treatment assignment independent of participants’ measured and unmeasured characteristics, on average. In a randomized comparison, the groups can then be compared as assigned, subject to appropriate outcome measurement and analysis. Randomization does not guarantee that every characteristic will be balanced in a particular study, especially in a small trial. The registry identifies random allocation and a parallel-group model, but does not report the sequence-generation or allocation-concealment methods. It also does not report a statistical adjustment plan.

What does the endpoint scale represent?

As a general statistical matter, endpoint form determines which summaries and methods are suitable. A score formed from ordered grades can be treated in several ways, but each approach answers a somewhat different question. A numerical score comparison concerns the score’s location or average, while a category-based comparison concerns the distribution across defined groups. A percentage of participants requires a clear rule defining who is counted in the numerator. The registry description gives site-level grades and a summed score, but does not state a cutpoint for classifying participants as having an event. It also labels the unit as percentage of participants. That makes it difficult to identify the intended primary analysis from the record alone.

The sum of site-specific grades provides a single summary across the described sites, but a total score can conceal different patterns. For instance, the same total could arise from different combinations of site severity. This is a general property of summed scores, not a claim about the participants in this trial. The registry’s endpoint description does not say whether site-specific outcomes were also intended for separate analysis, or how the named retrosternal endpoint relates to the broader multi-site score.

What would a confidence interval show?

In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, while the interval’s location helps show which effect sizes remain compatible with the data and method. The interval does not remedy problems such as an unclear endpoint definition, missing outcome data, or a mismatch between the analysis and the study question. No primary effect estimate or confidence interval is reported in the registry information available for this analysis, so no trial-specific precision statement can be made.

What does a significance test contribute?

In general, a significance test evaluates how compatible the observed data are with a specified null hypothesis, given the test’s assumptions. A p-value is not the probability that the null hypothesis is true, and it does not describe the size or clinical importance of an effect. A test result also cannot replace an effect estimate and its uncertainty. The registry records 0 analyses, and does not report a primary-outcome test or p-value. The exact hypothesis, test, and decision rule are not reported in the registry record.

Why does the analysis plan matter?

General statistical practice calls for defining the outcome, comparison, analysis population, and missing-data approach before examining trial results. Prespecification can reduce the risk that many plausible analysis choices are tried and only a favorable result is emphasized. It also makes it easier to interpret whether the reported estimate addresses the original question. The registry entries do not describe a statistical analysis plan, planned interim analyses, or how multiplicity across outcomes was handled. Those matters should not be inferred from the randomized design or study phase.

The sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is specified as a fraction of the observed effect. The record does not provide numerical planning outputs in the registry record for this analysis. Such planning quantities, when presented, are illustrations for a future study under stated assumptions, not observed power for the completed trial. They do not establish that the original design used those assumptions or that the trial had a particular probability of detecting an effect.

For count outcomes, analysis may require attention to the amount of exposure or time at risk, depending on how the outcome is defined. General methods for count data may also need to account for over-dispersion, where variability exceeds what a simple model assumes. Over-dispersion can lead to intervals that are too narrow and tests that are too optimistic if ignored. These are general considerations; the registry does not report a count-data analysis or model for the drainage outcome.

For binary outcomes, a comparison may be expressed using a difference in proportions, a ratio of proportions, or an odds-based measure. Each effect scale has a distinct interpretation, and the choice should reflect the outcome definition and analysis plan. No primary effect scale or statistical model is reported in the registry record. It would therefore be inappropriate to derive or select a measure from the descriptive endpoint wording alone.

Finally, an analysis of a randomized trial can use participants as assigned, or it can be limited to those who completed particular procedures or measurements. These populations answer different questions and can be vulnerable to different biases. The registry entries do not state which analysis population was planned or used. They also do not report how adherence, withdrawals, or unavailable second-stage assessments were addressed. These omissions limit what can be concluded about the intended statistical methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 0 analyses. It identifies adhesion severity as the primary outcome, hospital stay as a secondary outcome, and describes bleeding assessment through postoperative surgical-site drainage output. However, the registry entries do not show the results or analysis plan for these outcomes. The record does not report whether the primary outcome was assigned a single confirmatory test or whether adjustments for multiple outcomes or comparisons were planned. Multiplicity procedures are not reported in the registry record.

Missing-data handling is also not described. In particular, the record does not state how an unavailable adhesion assessment at the second staged surgery would be treated, whether participants without a measured outcome would be included in any analysis, or whether any imputation or sensitivity analyses were planned. These are open questions, not evidence that data were missing or that a particular method was used.

The analysis population is not specified in the registry record for this analysis. The record does not say whether results were to be analyzed according to randomized assignment, according to treatment received, or among participants with an observed outcome. These distinctions matter because excluding participants after randomization can weaken the protection that randomization provides. No conclusions about exclusions, protocol deviations, or attrition can be drawn from the enrollment figure alone.

The endpoint definition itself affects the multiplicity and missing-data questions. The primary title names retrosternal severity, while the description refers to summed scores from seven sites and gives a percentage-based unit. The registry does not explain which representation governed the primary analysis. Consequently, the number and nature of the planned primary comparisons are not reported in the registry record.

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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest unrelated to device (15.8%).

The registry lists serious adverse events by group as descriptive counts. In the No CoSeal Surgical Spray group, 1 serious event is listed among 16 participants at risk. In the CoSeal Spray Group, 3 serious events are listed among 19 participants at risk. The record lists 0 other adverse events among 16 at risk in the No CoSeal group and 0 among 19 at risk in the CoSeal group. These are the registry’s recorded figures; they are not a statistical comparison.

The registry also lists “Cardiac Arrest unrelated to device” at 15.8% among the top serious terms. The registry entries do not identify the group associated with that percentage or provide a group-specific breakdown for the term. The phrase “unrelated to device” is part of the term as recorded and should not be treated as a broader causal analysis of all events.

Counts alone do not show whether an apparent difference is precise or compatible with chance variation. No confidence interval, comparative test, event-timing detail, or adjudication method is reported in the registry record. The figures should therefore be read as safety descriptions recorded by arm, not as proof of a causal difference or equivalence.

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

The registry record describes a trial designed to compare CoSeal Surgical Spray with no spray in children undergoing staged surgical reconstruction. It specifies a planned assessment of adhesion severity at a later surgery, as well as bleeding assessed through postoperative drainage output. These details identify the study question and the intended clinical context. They do not, by themselves, establish what happened to the measured outcomes.

No numerical primary-outcome comparison, effect estimate, confidence interval, or test result is reported in the registry record for this analysis. Therefore, the record does not establish the direction, magnitude, or precision of any difference in adhesion severity between the randomized groups. It also does not provide a numerical result for bleeding based on drainage output or for hospital stay. A missing result should not be read as showing that the groups had the same outcomes.

The endpoint wording also limits interpretation. The title identifies severity at the retrosternal site, whereas the description gives a sum across seven sites and labels the unit as percentage of participants. The registry does not state the threshold or analysis definition needed to connect these descriptions. Without that clarification and an outcome estimate, the clinical meaning of a primary comparison cannot be judged.

The serious adverse event counts are descriptive and do not settle whether the groups differed in safety. The record provides no comparative uncertainty estimate or test, and its top serious term is not linked to a group-specific breakdown in the registry entries. The trial’s completed status does not substitute for reporting its outcome analyses. Overall, the registry record supports a description of the design, outcome definitions, and recorded safety counts, but not a conclusion about a treatment effect.

13. Why This Trial Matters Statistically

This trial raises statistical questions that are important in surgical studies with outcomes assessed at a later procedure. The primary adhesion assessment is planned during the second staged surgery, so interpretation depends on a clearly defined measure and on knowing which participants had an assessment. The registry describes a multi-site score but titles the outcome by one site and labels the unit as a percentage of participants. Clarifying that relationship is essential because the outcome definition determines what a group comparison means.

Randomized allocation is an important design feature because it can support a fair comparison between groups. But a design label alone does not tell readers how allocation was implemented, how masking worked, or how the results were analyzed. The record uses both “single” masking and “open-label, blinded-evaluator” wording without identifying the masked role. Reporting these details helps readers assess possible biases in intervention delivery and outcome assessment.

Outcome reporting is equally important. The registry lists 8 outcome measures but records 0 analyses in the registry record for this analysis. Without estimates and uncertainty intervals, readers cannot distinguish a large, precise difference from a small, imprecise one, or assess compatibility with no difference. Transparency about analysis populations and missing data would further show whether the comparison preserved the randomized design.

The safety entries illustrate why descriptive counts need context. Group-specific counts can identify what was recorded, but by themselves do not quantify uncertainty or establish causation. Taken together, these features make the registry record useful for understanding the planned question while highlighting the need for clear endpoint definitions, analysis methods, and results for 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 main limitation for interpreting this trial from the registry record is the absence of a reported primary-outcome estimate and analysis. The registry entries available for this analysis provide no group comparison, confidence interval, or test result for adhesion severity. They also do not provide numerical results for drainage output or hospital stay. The completed status does not resolve the absence of outcome results.

The primary endpoint’s description is not fully aligned internally: the title refers to retrosternal-site severity, while the measure description refers to a summed score across seven sites. The unit is stated as percentage of participants, but no classification threshold is described. This makes the intended primary outcome summary unclear. The record does not clarify whether the score was analyzed as a numerical scale, categorized, or otherwise transformed.

The registry describes the study as open-label with a blinded evaluator, while its masking entry says single masking. It does not specify who was masked or how masking was implemented. The record also does not report the randomization sequence method, allocation concealment, baseline group characteristics, adherence, or detailed eligibility criteria. These items are not reported in the registry record and should not be assumed.

Although the registry lists 8 outcome measures, the registry entries record 0 analyses. There is no stated statistical analysis plan, multiplicity approach, missing-data procedure, or analysis population. The serious adverse event entries are descriptive; no comparative uncertainty analysis is reported. Finally, the listed enrollment and group-level adverse-event denominators do not provide a complete account of follow-up for the primary endpoint. These limitations restrict assessment of both the validity and precision of any treatment comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery — NCT01330433.
• Registry record last updated 2016-12-15; status last verified 2016-10.
• Results first posted 2016-08-25.
• 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 identifies NCT01330433 as a completed Phase 2 randomized parallel-group study sponsored by Loma Linda University. Enrollment is listed as 35. The study compares CoSeal Surgical Spray, applied at the end of the first staged procedure, with no CoSeal Surgical Spray at that point in children undergoing staged surgical reconstruction.

The primary outcome is titled severity of adhesions at the retrosternal site. Its description details grades at seven sites and a summed score, with assessment during approximately the first 30-60 minutes of the second staged surgery. The record also describes postoperative drainage output as a bleeding measure and lists hospital stay as a secondary outcome.

The registry entries available for this analysis include no primary-outcome estimate or analysis results. The record lists serious adverse event counts by group and a top serious term, but no comparative safety analysis. The endpoint definition, masking details, analysis population, missing-data handling, and statistical analysis plan are not reported in the registry record.