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 Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease (NCT03395639), a randomized phase 3 study. The primary outcome is Number of Participants With Adjudicated Bleeding Events Within the Main Treatment Period.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03395639 |
| Phase | Phase 3 |
| Condition | Cardiac Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 168 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Daiichi Sankyo |
| Results posted | Yes |
2. Clinical Question
Population
Children from 38 weeks gestational age to less than 18 years of age with cardiac diseases and risk of thromboembolic events. The primary endpoint was assessed in participants in the Safety Analysis Set during the Main Treatment Period.
Intervention
Edoxaban, given as a solution or tablets. The registry describes random assignment to edoxaban or the institution's standard-of-care regimen.
Comparator
Standard of care (SOC), defined as the institution's SOC regimen for preventing blood clots. The registry does not specify the regimens used at participating institutions.
Primary question
How many participants had adjudicated bleeding events during the Main Treatment Period, which included major and clinically relevant non-major bleeding? The posted the registry entries do not include a primary-endpoint result by treatment arm or a statistical comparison for that endpoint.
The trial concerned children with cardiac disease considered at risk of thromboembolic events. Its stated purpose was to evaluate the safety and efficacy of edoxaban against standard care. The primary outcome named in the record is a count of participants with adjudicated bleeding, rather than a measure of clot prevention. It includes major and clinically relevant non-major bleeding during the specified treatment period.
The primary outcome is therefore one part of the safety and efficacy question, not a complete account of either. The registry lists secondary outcomes concerning symptomatic thromboembolic events in systemic arterial or venous pathways, deaths resulting from thromboembolic events, all-cause deaths, and events during an extension period. Names of those outcomes are reported, but their results are not reported in the registry record. The primary comparison's arm-level counts and inferential statistics are also not reported in the registry record, so the record does not permit a numerical estimate of the treatment contrast for the primary question.
3. Trial Design
The registry identifies NCT03395639 as a Phase 3, randomized, open-label, parallel-group, multicentre trial. Its official title also uses the term observational trial, although the registry fields describe randomized allocation and two treatment arms. That difference in terminology is present in the record; an explanation is not reported in the registry record. The listed enrollment is 168, and the trial status is completed.
The study compared edoxaban with standard of care for prevention of blood clots. The arm descriptions state that two out of three participants would be randomized to edoxaban solution or tablets and one out of three to the institution's SOC regimen. These descriptions indicate an unequal allocation plan. The registry's general study summary likewise describes those chances. Treatment masking is listed as none, so this was an open-label comparison rather than a masked one.
The recorded start date is 2018-05-15, and the primary completion date is 2021-12-03. The Main Treatment Period for the primary endpoint runs from the first dose up to Month 4, or to the last dose if study treatment was discontinued, whichever was earlier. The registry also reports an Extension Period, including an edoxaban-only group in its adverse-event information. Further details about extension eligibility, treatment assignment, or follow-up procedures are not reported in the registry record.
Because the trial was open-label, participants and study staff were not masked to treatment assignment according to the masking field. The primary bleeding endpoint was adjudicated, but details of the adjudication process beyond the stated event definitions are not reported in the registry record. The record names Daiichi Sankyo as sponsor. It does not report enough information to characterize sites, recruitment procedures, treatment doses, or the institution-specific contents of standard care.
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: All subjects at the Screening Visit were assessed for international normalized ratio (INR) and activated partial thromboplastin time (aPTT) and evaluated at the local laboratory.
Main Treatment Period (0 to 4 Months)
| Stage | Main Treatment Period: Edoxaban | Main Treatment Period: Standard of Care (SOC) | Extension Period: Edoxaban Only |
|---|---|---|---|
| STARTED | 110 | 58 | 0 |
| Modified Intent to Treat Population | 109 | 58 | 0 |
| COMPLETED | 107 | 55 | 0 |
| NOT COMPLETED | 3 | 3 | 0 |
Reasons for not completing this period:
| Reason | Main Treatment Period: Edoxaban | Main Treatment Period: Standard of Care (SOC) | Extension Period: Edoxaban Only |
|---|---|---|---|
| Withdrawal by Subject | 2 | 2 | 0 |
| Adverse Event | 1 | 0 | 0 |
| Participant discontinued at Principal Investigator discretion | 0 | 1 | 0 |
Extension Period (4-13 Months)
| Stage | Main Treatment Period: Edoxaban | Main Treatment Period: Standard of Care (SOC) | Extension Period: Edoxaban Only |
|---|---|---|---|
| STARTED | 0 | 0 | 147 |
| COMPLETED | 0 | 0 | 144 |
| NOT COMPLETED | 0 | 0 | 3 |
Reasons for not completing this period:
| Reason | Main Treatment Period: Edoxaban | Main Treatment Period: Standard of Care (SOC) | Extension Period: Edoxaban Only |
|---|---|---|---|
| Adverse Event | 0 | 0 | 2 |
| Subject discontinued at PI discretion | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Adjudicated bleeding events were assessed in participants in the Safety Analysis Set within the Main Treatment 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.
Population: Demographic and baseline characteristics were assessed in the Intent to Treat Population (ITT).
| Characteristic | Unit | Edoxaban | Standard of Care (SOC) | Total |
|---|---|---|---|---|
| Participants analysed | 110 | 58 | 168 | |
| Age, Continuous | years | 7.7 (SD 4.8) | 7.3 (SD 5.1) | 7.6 (SD 4.9) |
| Age, Customized: 0 to 6 months | Participants | 1 | 3 | 4 |
| Age, Customized: 6 months to <2 years | Participants | 7 | 5 | 12 |
| Age, Customized: 2 to <6 years | Participants | 33 | 17 | 50 |
| Age, Customized: 6 to <12 years | Participants | 41 | 17 | 58 |
| Age, Customized: 12 to <18 years | Participants | 28 | 16 | 44 |
| Sex: Female, Male: Female | Participants | 38 | 21 | 59 |
| Sex: Female, Male: Male | Participants | 72 | 37 | 109 |
| Race/Ethnicity, Customized: Asian | Participants | 6 | 3 | 9 |
| Race/Ethnicity, Customized: Black or African American | Participants | 4 | 3 | 7 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Native Hawaiian/Pacific Islander | Participants | 2 | 1 | 3 |
| Race/Ethnicity, Customized: White | Participants | 80 | 39 | 119 |
| Race/Ethnicity, Customized: Other | Participants | 10 | 7 | 17 |
| Race/Ethnicity, Customized: Unknown | Participants | 8 | 5 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adjudicated Bleeding Events Within the Main Treatment Period, measured over Date of first dose of study drug up to the Month 4 or to the date of last dose of study drug if study treatment was discontinued, whichever was earlier.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adjudicated bleeding events within the Main Treatment Period. It counts participants, not the total number of bleeding episodes. The record says events were assessed in the Safety Analysis Set. The observation window starts at the first dose of study drug and continues up to Month 4, or up to the date of the last dose if treatment was discontinued, whichever was earlier.
The endpoint combines major bleeding and clinically relevant non-major (CRNM) bleeding under the stated International Society on Thrombosis and Haemostasis (ISTH) definitions. Major bleeding includes fatal bleeding, symptomatic bleeding in a critical area or organ, or bleeding causing a decrease in hemoglobin level of >2 g/dL or leading to transfusion of the equivalent of ≥2 units of whole blood or red cells. A CRNM bleed does not meet major-bleeding criteria but prompts a clinical response, such as hospital admission for bleeding, physician-guided medical or surgical treatment, or a change in antithrombotic therapy. Other overt bleeding that meets neither category is described as minor bleeding and is not included in the primary endpoint definition.
Safety endpoints commonly help describe harms observed during treatment and are especially relevant when comparing antithrombotic strategies. That is a general explanation; the registry does not state a rationale for selecting this particular primary endpoint. The primary endpoint result by arm, its treatment contrast, and its confidence interval are not reported in the registry record. Therefore, the endpoint definition can be described, but the comparative primary-endpoint finding cannot be reconstructed from the registry information available for this analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison but does not report the arm-level results for the primary outcome of adjudicated bleeding during the Main Treatment Period. It also does not report a primary-endpoint treatment effect, confidence interval, or p-value. Consequently, the record does not establish the size or precision of a difference between edoxaban and standard of care for this endpoint. No conclusion about comparative safety or efficacy should be inferred from an endpoint definition alone.
The adverse-event counts offer a separate descriptive view. During the Main Treatment Period, the registry lists 5 serious adverse events among 109 participants at risk in the edoxaban group and 3 among 58 at risk in the SOC group. The corresponding counts for other adverse events are 51 among 109 and 24 among 58. These are counts as reported in the adverse-event fields; the record does not identify these totals as the primary adjudicated-bleeding outcome. Serious adverse events and the primary bleeding endpoint are not interchangeable measures.
For the Extension Period, the registry lists edoxaban only, with 19 serious adverse events among 144 participants at risk and 69 other adverse events among 144. The record lists 2 deaths in that group. It does not report an extension-period SOC comparison in these figures. Nor does the registry information state whether any of these deaths were caused by thromboembolic events or provide the clinical context needed to attribute them to treatment.
Percentages for selected serious adverse-event terms are listed, including Cardiac failure and Pleural effusion at 1.8%, Vomiting and Hyponatraemia at 1.7%, Pulmonary embolism at 1.7%, and Pyrexia at 1.4%. These terms are descriptive entries, not evidence by themselves of a treatment-related effect. The registry does not provide arm-specific comparative estimates for each term in the registry record analyzed.
These data should be read as descriptive counts with denominators, not as a complete comparative analysis. A confidence interval, in general, expresses the statistical uncertainty around an estimated effect; none for the primary outcome is reported in the registry record. Without the primary outcome counts and inferential results, the magnitude and precision of the randomized comparison remain unavailable. The record's reported event counts cannot substitute for those missing results, and they do not establish causation.
9. Statistical Methods Explained
The study is described as randomized, open-label, parallel-group, and multicentre. Random assignment is intended, in general, to make treatment groups comparable on average with respect to factors measured and unmeasured at baseline. It does not guarantee that the realized groups will be identical. An open-label design means treatment assignment was not masked according to the registry field. Knowledge of assignment can affect care, reporting, or assessment, although an adjudicated outcome may use review procedures to classify events. The exact safeguards and adjudication process are not reported in the registry record.
What the endpoint counts
The primary endpoint counts participants who experienced adjudicated bleeding during the Main Treatment Period. A participant-count endpoint differs from an event-count endpoint: multiple episodes in one participant need not increase the number of participants with an event. The record describes the endpoint as including major and CRNM bleeding, using modified ISTH recommendations. Major bleeding includes fatal bleeding, symptomatic bleeding in a critical area or organ, or bleeding associated with a decrease in hemoglobin level of >2 g/dL or transfusion of the equivalent of ≥2 units of whole blood or red cells. CRNM bleeding is overt bleeding that does not qualify as major but prompts a clinical response, with examples including hospital admission, physician-guided treatment, or change in antithrombotic therapy.
The endpoint's time window begins with the first dose and ends at Month 4 or the last dose if treatment was discontinued, whichever is earlier. Defining a window makes clear which events are eligible for the primary count. The registry does not report how participants with incomplete follow-up were handled, whether any endpoint observations were missing, or what analysis method was used to compare groups.
Descriptive counts and comparisons
The adverse-event information reports counts and the number of participants at risk for each listed group. Counts help describe the number of participants affected; denominators give context about the group being described. A count alone is not a comparative treatment effect. A formal comparison would require the endpoint data for each relevant group and a specified statistical analysis. For the primary endpoint, arm-specific counts and comparative estimates are not reported in the registry record.
In general, a confidence interval describes a range of values compatible with the observed data under a statistical model and reflects uncertainty in an estimate. A p-value is a measure calculated under a null hypothesis and a specified analysis; it does not convey the size or clinical importance of an effect. Neither a primary-endpoint confidence interval nor a p-value is reported in the registry entries analyzed. It is therefore not possible to describe the precision or statistical evidence for a primary endpoint contrast.
The record identifies eight outcome measures and three analyses, but does not give the corresponding analysis details or results in the information used for this explanation. The primary endpoint is a count outcome, and the posted event information does not establish whether the trial's prespecified analysis used a risk difference, risk ratio, odds ratio, time-to-event method, or another measure. The statistical model, covariate adjustment, handling of repeated events, and any stratification are not reported in the registry record.
Planning illustrations
A planning illustration can show, in general, how sample size depends on assumptions about the effect to detect, allocation, significance level, and statistical method. It is not an observed trial result and is not observed power. The planning assumptions stated for this analysis use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those assumptions are described as a planning illustration rather than the trial's own design. The trial's sample-size justification and design assumptions are not reported in the registry record. Numerical planning estimates are not reported in the registry entries analyzed here, so no required number of participants per arm can be stated.
In general, over-dispersion means that observed variation is greater than a model's assumed variation. It can make standard errors too small if the model does not account for it. That concept is relevant to some count-data analyses, but the registry does not report an over-dispersion assessment or identify a count model for the primary endpoint. This is a general statistical explanation, not a claim about the analysis used in this trial.
What can be concluded from the available analysis details
The trial's randomized design and endpoint definition are described, as are selected adverse-event counts. However, design labels do not replace outcome results. Without the primary outcome counts, analysis population details beyond the stated Safety Analysis Set, and an inferential analysis, a numerical treatment effect cannot be interpreted. Any further statistical plan—including interim analyses, multiplicity control, missing-data methods, or sensitivity analyses—is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures, including the primary bleeding outcome and secondary outcomes involving thromboembolic events, deaths, bleeding, and extension-period events. Considering several outcomes can raise a multiplicity issue: in general, the more statistical tests conducted, the greater the chance of at least one apparently unusual finding under a set of null hypotheses. A prespecified testing hierarchy or adjustment can address some multiplicity concerns. Whether this trial used a hierarchy, adjustment, or other multiplicity strategy is not reported in the registry record.
The record indicates three analyses, but their methods and relationship to the listed outcomes are not reported in the registry entries. It does not state whether analyses were interim or final, whether any stopping rules applied, or whether the primary endpoint had a single prespecified test. Those details should not be inferred from the existence of analysis entries alone.
The primary endpoint population is described as participants in the Safety Analysis Set during the Main Treatment Period. The registry does not report the full definition of that set, the randomized and analyzed counts for the primary endpoint by arm, or how missing observations were handled. It also does not report whether participants were analyzed according to randomized assignment, treatment received, or another population definition. Missing-data methods, censoring rules, sensitivity analyses, and the extent of missing outcome data are not reported in the registry record.
These omissions limit assessment of the robustness and completeness of the primary comparison. They do not show that data were missing or that multiplicity adjustments were absent; they mean the relevant procedures are not reported in the registry record. The listed secondary outcomes likewise lack numerical results in the registry record analyzed here, preventing a broader statistical reading across outcomes.
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 |
|---|---|---|---|
| Main Treatment Period: Edoxaban | 5 | 109 | 4.6% |
| Main Treatment Period: Standard of Care (SOC) | 3 | 58 | 5.2% |
| Extension Period: Edoxaban Only | 19 | 144 | 13.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Main Treatment Period: Edoxaban | 0 of 109 |
| Main Treatment Period: Standard of Care (SOC) | 0 of 58 |
| Extension Period: Edoxaban Only | 2 of 144 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Main Treatment Period: Edoxaban | 51 of 109 |
| Main Treatment Period: Standard of Care (SOC) | 24 of 58 |
| Extension Period: Edoxaban Only | 69 of 144 |
Most frequent serious adverse event terms
| Event term | Organ system | Main Treatment Period: Edoxaban | Main Treatment Period: Standard of Care (SOC) | Extension Period: Edoxaban Only |
|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | 2 of 109 | 1 of 58 | 0 of 144 |
| Vomiting | Gastrointestinal disorders | 0 of 109 | 1 of 58 | 1 of 144 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 2 of 109 | 0 of 58 | 0 of 144 |
| Pyrexia | General disorders | 0 of 109 | 0 of 58 | 2 of 144 |
| Coronary artery thrombosis | Cardiac disorders | 1 of 109 | 0 of 58 | 0 of 144 |
| Hyponatraemia | Metabolism and nutrition disorders | 0 of 109 | 1 of 58 | 0 of 144 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 109 | 1 of 58 | 0 of 144 |
| Haemolysis | Blood and lymphatic system disorders | 0 of 109 | 0 of 58 | 1 of 144 |
| Immune thrombocytopenia | Blood and lymphatic system disorders | 0 of 109 | 0 of 58 | 1 of 144 |
| Atrial thrombosis | Cardiac disorders | 0 of 109 | 0 of 58 | 1 of 144 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Main Treatment Period: Edoxaban | Main Treatment Period: Standard of Care (SOC) | Extension Period: Edoxaban Only |
|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | 14 of 109 | 2 of 58 | 9 of 144 |
| Pyrexia | General disorders | 5 of 109 | 1 of 58 | 13 of 144 |
| Headache | Nervous system disorders | 5 of 109 | 2 of 58 | 9 of 144 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 109 | 2 of 58 | 9 of 144 |
| Upper respiratory tract infection | Infections and infestations | 2 of 109 | 2 of 58 | 7 of 144 |
| Nasopharyngitis | Infections and infestations | 4 of 109 | 3 of 58 | 4 of 144 |
| Vomiting | Gastrointestinal disorders | 3 of 109 | 2 of 58 | 6 of 144 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 3 of 109 | 2 of 58 | 6 of 144 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 4 of 109 | 1 of 58 | 3 of 144 |
| Bronchitis | Infections and infestations | 3 of 109 | 0 of 58 | 3 of 144 |
Serious events with the highest arm-level rate: cardiac failure (1.8%), pleural effusion (1.8%), vomiting (1.7%), hyponatraemia (1.7%), pulmonary embolism (1.7%).
The adverse-event entries give counts of participants at risk, participants affected by serious adverse events, participants affected by other adverse events, and deaths for the listed groups. During the Main Treatment Period, the edoxaban group has 109 participants at risk, 5 with serious adverse events, 51 with other adverse events, and 0 deaths. The SOC group has 58 participants at risk, 3 with serious adverse events, 24 with other adverse events, and 0 deaths. These are registry counts and should not be read as the adjudicated primary bleeding endpoint.
For the Extension Period, the entry is Edoxaban Only: 144 participants at risk, 19 with serious adverse events, 69 with other adverse events, and 2 deaths. The record does not provide a corresponding extension-period SOC group in these adverse-event entries. It also does not state in the registry record whether the reported deaths were related to treatment, thromboembolic events, or another cause.
Serious adverse events are distinct from the endpoint's defined major and CRNM bleeding categories. The record lists selected serious adverse-event terms with percentages, including Cardiac failure and Pleural effusion at 1.8%, Vomiting and Hyponatraemia at 1.7%, Pulmonary embolism at 1.7%, and Pyrexia at 1.4%. The definitions and event attribution details for these terms are not reported in the registry record. These figures describe events recorded in the listed groups; they do not by themselves establish causation or a comparative treatment effect.
12. What the Result Does, and Does Not, Mean
The registry record establishes the trial's stated question, randomized open-label design, primary endpoint definition, and selected adverse-event counts. It does not report the primary endpoint result by treatment arm or an estimate of the difference between edoxaban and standard of care. Thus, it is not possible to quantify the comparative frequency of adjudicated bleeding from the available registry information. The same limitation applies to the listed secondary outcomes: their names appear, but their numerical results are not reported in the registry record.
The adverse-event counts can be described for the periods and groups listed, but they do not fill the gap in the primary analysis. Serious adverse events, other adverse events, deaths, and adjudicated bleeding are different categories. Their definitions, periods of observation, and purposes are not interchangeable. In particular, the Main Treatment Period counts should not be treated as results for the primary bleeding endpoint unless the record explicitly identifies them that way; it does not.
A randomized comparison is designed to support causal interpretation under appropriate conduct and analysis, but the design label alone is not enough to estimate an effect. Arm-level endpoint results, analysis methods, and measures of uncertainty are needed to assess the size and precision of a contrast. Those primary comparative details are not reported in the registry record. Similarly, a lack of reported primary results does not demonstrate that no difference occurred; it means the comparative result cannot be evaluated from these registry entries.
The listed deaths in the extension group are descriptive. Their number does not establish a cause, relationship to edoxaban, or comparative risk, particularly because the adverse-event entries do not include an extension-period SOC comparator. The registry lists other outcomes that could address thromboembolic events and mortality, but their results are not reported in the registry record.
Accordingly, the record supports a description of the trial design and selected safety counts, not a definitive statement about whether one treatment had better outcomes. The endpoint definitions and counts are useful context, but a treatment conclusion would require the missing outcome results and analysis details.
13. Why This Trial Matters Statistically
This trial raises several statistical issues that matter when interpreting pediatric studies of therapies used to prevent thromboembolic events. The population spans children from 38 weeks gestational age to less than 18 years of age, a broad age range. The registry does not report age-specific outcome results, so it is not possible to determine from these registry entries whether event patterns or treatment effects differed across ages or clinical subgroups.
The comparison is randomized but open-label, with edoxaban and institution-specific standard care. Randomization is valuable for reducing systematic differences between assigned groups in expectation. At the same time, an open-label design and variation in SOC regimens can make outcome assessment and interpretation more dependent on clear definitions and consistent procedures. The endpoint is described as adjudicated, but the adjudication procedures and details about SOC regimens are not reported in the registry record.
The primary endpoint measures bleeding, while the trial's stated purpose also concerns prevention of thromboembolic events. This distinction matters: safety and efficacy outcomes address different questions, and neither can stand in for the other. The record lists secondary thromboembolic and mortality outcomes, but their numerical findings are not reported in the registry entries analyzed. A complete statistical assessment would need the relevant event counts, comparisons, and uncertainty estimates across those outcomes.
The main and extension periods also answer different descriptive questions. The extension adverse-event group is identified as edoxaban only, so those entries do not supply a contemporaneous SOC comparison. Interpreting changes across periods as treatment effects would require more information about follow-up and group membership, which is not reported in the registry record.
Finally, the absence of primary comparative results highlights the difference between a trial's design and its reported evidence. Sample size, endpoint definitions, and randomization describe how a study is framed; they do not reveal the observed treatment contrast. Statistical interpretation depends on complete outcome reporting, analysis methods, and precision estimates, none of which can be inferred from the design alone.
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 central limitation for interpretation is that primary-endpoint results are not reported in the registry record. No arm-specific count of participants with adjudicated bleeding, comparative effect estimate, confidence interval, or p-value is included in the registry record analyzed. Consequently, the main randomized comparison cannot be quantified or assessed for precision.
The registry identifies the Safety Analysis Set as the population for the primary endpoint, but does not provide its full definition or the number analyzed in each arm for that endpoint. Missing-data handling, analysis according to randomized assignment or treatment received, censoring, and sensitivity analyses are not reported. The effect of any missing or excluded observations therefore cannot be assessed.
The trial is described as open-label and randomized, while its official title calls it observational. The record does not explain this terminology difference. The primary outcome is adjudicated, but the adjudication process is not detailed beyond the endpoint definitions. The institution-specific SOC regimens are also not described, limiting characterization of the comparator.
For adverse events, the record gives counts for the Main Treatment Period and an edoxaban-only Extension Period, but it does not give an extension-period SOC comparison in those entries. The listed death count in the extension group is not accompanied by cause or attribution details in the analyzed details. Selected serious adverse-event terms and percentages are descriptive and do not provide a full comparative assessment.
The record lists secondary outcomes but does not report their numerical results in the information analyzed. It also does not report the trial's sample-size justification, statistical analysis plan, multiplicity strategy, or interim-analysis procedures. These are reporting limitations for interpreting the registry entries; they do not establish that the trial lacked such procedures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease — NCT03395639.
- Registry record last updated 2022-07-26; status last verified 2022-07.
- Results first posted 2022-07-26.
- 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
NCT03395639 is recorded as a completed Phase 3 randomized, open-label, parallel-group, multicentre study sponsored by Daiichi Sankyo. It enrolled 168 children from 38 weeks gestational age to less than 18 years of age with cardiac disease and risk of thromboembolic events. The recorded start date is 2018-05-15, and the primary completion date is 2021-12-03.
The comparison was edoxaban solution or tablets versus the institution's standard-of-care regimen. The primary endpoint was the number of participants with adjudicated major or clinically relevant non-major bleeding during the Main Treatment Period, assessed in the Safety Analysis Set. The record also lists secondary thromboembolic, mortality, and extension-period outcomes.
Selected adverse-event counts are reported for the Main Treatment Period and for an edoxaban-only Extension Period. The primary endpoint's arm-level results and comparative statistical analysis are not reported in the registry record, so the primary treatment contrast cannot be evaluated in the registry record analyzed.