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 Response of Recombinant Antithrombin in Heparin Resistant Patients Undergoing Cardiac Surgery (NCT01547728), a na phase 4 study. The primary outcome is Percentage of Patients Whose Activated Clotting Time (ACT) is Prolonged Beyond 480 Seconds With Recombinant Human Antithrombin Concentrate (rhAT) Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01547728 |
| Phase | Phase 4 |
| Condition | Thrombophilia Due to Acquired Antithrombin III Deficiency |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
Patients described in the study objective as heparin resistant and scheduled to undergo cardiac surgery. The registry lists acquired antithrombin III deficiency as the condition. Further eligibility details and the number of participants who actually received treatment are not reported in the registry record.
Intervention
Intravenous recombinant human antithrombin (rhAT), identified as ATRYN. The arm description specifies an initial bolus of 500 units. If a subject remained heparin resistant, the description allows one additional intravenous bolus of 500 units.
Comparator
There was no separate comparator arm in the registered design. The study is classified as single-group, and allocation is listed as not applicable. The registry therefore does not describe a like-for-like control comparison.
Primary question
The primary question was whether the activated clotting time (ACT) exceeded 480 seconds 3 minutes after the initial rhAT dose, and what percentage of patients met that criterion. The planned summary was a point estimate with a 95% confidence interval. The endpoint result itself is not reported in the registry record.
This is a question about a defined laboratory response after treatment, not a comparison of treatment strategies. The endpoint uses a threshold: each participant would either meet the ACT criterion at the specified assessment time or not meet it. The registry describes the clinical setting and response rule, but it does not report the observed number meeting the rule, the number assessed, or an estimated percentage. Consequently, the registered question can be described, but its answer cannot be recovered from the posted results.
3. Trial Design
The registry describes a phase 4, single-group study sponsored by Mayo Clinic. It lists an enrollment of 42, but the number actually enrolled, treated, or included in an endpoint analysis is not reported in the registry record. The study start is listed as 2012-02 and primary completion as 2014-02. Its status is terminated. The registry states that termination occurred because there were too many barriers to enroll participants.
The intervention was recombinant human antithrombin. The arm description specifies an intravenous bolus of 500 units, with one more intravenous bolus of 500 units if the subject remained heparin resistant. This conditional dosing description does not establish how many participants received an additional dose; that information is not reported in the registry record.
Allocation is listed as not applicable, masking as none, and the model as single-group. There is therefore no registered control group against which to compare the response. The design can describe outcomes among people who received the intervention, if those outcomes and their denominators are available, but it cannot by itself separate an intervention-associated response from other explanations or estimate a between-group treatment contrast.
The study objective was to prospectively evaluate the response to recombinant antithrombin among heparin-resistant patients scheduled for cardiac surgery. The primary endpoint was an ACT threshold measured 3 minutes after the initial dose on Day 1 of the study. The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, the analysis population, the number of endpoint assessments, or the observed endpoint estimate. These gaps are important when judging what can be learned from 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 | Recombinant Antithrombin (rhAT) |
|---|---|
| STARTED | 42 |
| COMPLETED | 1 |
| NOT COMPLETED | 41 |
Reasons for not completing this period:
| Reason | Recombinant Antithrombin (rhAT) |
|---|---|
| Change in procedure and equipment | 1 |
| Drug not ready for subject | 1 |
| Screen failure | 39 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated because there were too many barriers to enroll participants.
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 | Recombinant Antithrombin (rhAT) |
|---|---|---|
| Participants analysed | 42 | |
| Age, Continuous | years | 64 (19 to 83) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 27 |
| Region of Enrollment: United States | participants | 42 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Patients Whose Activated Clotting Time (ACT) is Prolonged Beyond 480 Seconds With Recombinant Human Antithrombin Concentrate (rhAT) Administration, measured over 3 minutes after the initial dose of rhAT, Day 1 of the study.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of patients whose ACT was greater than 480 seconds 3 minutes after the initial dose of 500 units of recombinant human antithrombin. The registry identifies the assessment time as Day 1 of the study. In the protocol description, reaching the threshold is the operational definition of restored antithrombin level for this endpoint.
This is a binary response criterion at a specified assessment: a patient either meets the threshold or does not. Expressing the result as a percentage would describe how often the defined response occurred in the analyzed group. A point estimate gives the observed percentage, while a confidence interval communicates uncertainty around that estimate. In general, a confidence interval is a way to show how imprecisely an outcome proportion is estimated from the available data; it is not a guarantee that the true value lies within a particular range.
The registry says that a point estimate and a 95% confidence interval would be used, but neither is reported. The number assessed and the number meeting the ACT criterion are also not reported in the registry record. As a result, the endpoint definition and planned summary are known, but the response frequency and its precision cannot be evaluated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the primary endpoint has no posted result in the registry record. There is no reported point estimate for the percentage whose ACT exceeded 480 seconds at the specified assessment, and no reported 95% confidence interval. The registry gives the endpoint definition and the planned form of the summary, but not the observations needed to judge the response frequency or its uncertainty.
The registry lists enrollment as 42. That field does not establish how many participants entered the study, received rhAT, had an ACT measurement at the endpoint time, or were included in an analysis. Those counts are not reported in the registry record. Because the denominator and event count for the endpoint are unavailable, it would be inappropriate to infer a response percentage from the enrollment field.
The study was terminated because there were too many barriers to enroll participants. This provides a stated reason for termination, but it does not reveal how many participants had been enrolled or whether any endpoint data had been collected. Nor does it establish why the results are absent. The reason for termination should therefore be kept separate from claims about the treatment response.
The single-group design also limits interpretation. Even if the endpoint estimate were available, it would describe the proportion meeting the threshold in the observed group. There is no randomized or other registered comparator arm, so the study does not provide a direct estimate of how the outcome would differ under another treatment or under no intervention. The registry lists allocation as not applicable and masking as none; it does not describe a control comparison.
Precision would depend on the number of participants with endpoint assessments and the observed distribution of responses. Neither is available in the posted results. A confidence interval was planned, but its width and position cannot be assessed without the estimate and relevant data. General statistical interpretation distinguishes a lack of reported results from evidence of no response: absence of an estimate is not a zero estimate. The registry record supports no conclusion about the magnitude, consistency, or precision of the endpoint response.
Thus, the posted information identifies the clinical question, intervention, threshold, assessment time, and reason for termination. It does not answer the primary question statistically. Any conclusion about whether the threshold was commonly or rarely met, or about how precisely the percentage was estimated, would require information not reported in the registry record.
9. Statistical Methods Explained
The registered primary endpoint is a proportion. Each assessed participant is classified according to whether ACT exceeded the stated threshold at the stated time. A proportion is useful for a response criterion because it expresses the frequency of a prespecified category in the group being assessed. To interpret that proportion, however, the numerator (the number meeting the criterion) and denominator (the number assessed) must be known. Neither is reported in the registry record.
What does the planned confidence interval communicate?
The registry describes a point estimate and a 95% confidence interval for the percentage meeting the endpoint. In general, the point estimate summarizes the observed response proportion, and the confidence interval expresses the estimate's statistical uncertainty. An interval that is relatively narrow indicates greater precision than a wider interval, all else equal. The interval is not itself a treatment comparison, and it does not correct for limitations such as missing endpoint assessments or a lack of a comparator group.
Because the endpoint estimate and its confidence interval are not posted, their location and width cannot be assessed. The confidence level alone does not reveal whether the observed response was high or low, or whether the estimate was precise. The actual method used to construct the interval is not reported in the registry record. No particular interval procedure should be attributed to the study.
What does the single-group structure permit?
A single-group analysis can describe outcomes among participants with available measurements. It does not create a concurrent control group, and it cannot establish a randomized contrast. Here, allocation is listed as not applicable, masking as none, and the model as single-group. Accordingly, any endpoint result would need to be interpreted as a descriptive response in the analyzed group, not as a controlled estimate of a difference between treatments.
General statistical reasoning also distinguishes an observed response proportion from a causal effect. A response after an intervention is an observation; a causal comparison requires a credible estimate of what would have happened under a different condition. This registry record contains no registered comparator arm or comparative analysis. The endpoint was designed around a post-dose threshold, not a between-group contrast.
What do the planning assumptions mean?
The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes considering selected fractions of the observed effect. For time-to-event outcomes, the planning convention is a total event count; for other outcomes, it is participants per arm. These are planning conventions, not observed trial results and not the registered single-group design.
In general, a sample-size calculation translates assumptions about an effect, variability, allocation, and statistical error into a planning target. It is not an estimate of the trial's actual precision, and it is not observed power. A planning illustration based on an observed effect also depends on the effect estimate it uses. The posted primary outcome result and observed effect are not reported in the registry record, so the underlying effect cannot be independently evaluated from the information available. No sample-size illustration should be treated as proof that the terminated study had adequate or inadequate power.
Why does over-dispersion matter in general?
For count outcomes, over-dispersion means that the observed variability is greater than a model's assumed variability. If that feature is ignored, uncertainty may be understated and tests may appear more informative than they are. This is a general consideration for analyses of counts, not a reported feature of this study. The registered primary endpoint is a proportion, and the registry does not report an analysis model, a dispersion assessment, or any count-based primary analysis. Over-dispersion should not be presented as a study-specific finding.
What information is needed to assess the analysis?
Assessment would require the observed endpoint result, its denominator, the number meeting the ACT threshold, and the method used to calculate the confidence interval. It would also require clarity about which participants were included and how unavailable measurements were handled. The registry lists one outcome measure and zero analyses, but a count of listed measures or analyses does not supply those details. The statistical analysis plan, analysis population, missing-data approach, and any interim analyses are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure, identified as the primary endpoint, and zero analyses. That listing does not establish whether the study had additional outcomes or analyses outside the registry information, nor does it describe a prespecified statistical analysis plan. The approach to multiplicity is not reported in the registry record.
In general, multiplicity arises when multiple outcomes, comparisons, time points, or analyses are considered. If several statistical tests are used, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The record specifies an endpoint assessment 3 minutes after the initial dose on Day 1, but does not report whether other time points or exploratory analyses were planned or conducted. No multiplicity adjustment or testing hierarchy is reported, so none should be assumed.
Information on missing endpoint measurements is also not reported in the registry record. The stated termination reason concerns barriers to enrollment, but it does not say whether endpoint data were missing, how many participants lacked measurements, or how missingness was handled. The number analyzed and the analysis population are not reported. It is therefore not possible to determine whether the reported enrollment field corresponds to participants with an evaluable endpoint.
In general, missing-data methods can affect a proportion estimate when participants without outcome measurements differ from those assessed. A complete-case estimate, an imputation approach, and other strategies rely on different assumptions. The registry does not identify which, if any, approach was used. Interim analyses and stopping rules are also not reported in the registry record. These omissions limit assessment of how the intended analyses were conducted and how representative any possible endpoint estimate would be.
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 |
|---|---|---|---|
| Recombinant Antithrombin (rhAT) | 0 | 1 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Recombinant Antithrombin (rhAT) | 0 of 1 |
The safety record lists a recombinant antithrombin group. For serious adverse events, it reports 1 at risk and 0 affected. For other adverse events, it also reports 1 at risk and 0 affected. The deaths field is null, so deaths are not reported in the registry record. No serious adverse-event terms are listed.
These entries should be read as the figures recorded in the registry, not as a complete account of safety in the study. The at-risk counts are not consistent with interpreting the registry enrollment field as the safety denominator, and the number of participants included in safety reporting is not explained. The registry does not report the duration or completeness of safety follow-up, or whether the figures reflect all participants who received the intervention.
A recorded count of 0 affected is not, on its own, evidence that no events occurred among all study participants. It is a reported figure whose scope depends on the safety population and reporting completeness, neither of which is described. Likewise, the absence of listed serious-event terms does not establish that no serious events occurred. The figures should therefore be treated as limited registry reporting rather than as a basis for a broad safety conclusion.
12. What the Result Does, and Does Not, Mean
The record establishes that the study asked whether ACT exceeded 480 seconds 3 minutes after an initial dose of recombinant human antithrombin in heparin-resistant patients scheduled for cardiac surgery. It also records a planned point estimate and 95% confidence interval for the percentage meeting that criterion. These details define the intended endpoint and its timing.
The record does not report the observed endpoint percentage, its confidence interval, the number of participants assessed, or the number who met the threshold. Consequently, it cannot show how often the defined response occurred or how precisely that frequency was estimated. The listed enrollment of 42 does not replace those missing outcome data.
Even with a reported proportion, this single-group design would describe the observed response in the assessed group rather than provide a direct comparison with another treatment or a control condition. The record lists no comparator arm. It therefore cannot, on its own, establish the effect of rhAT relative to an alternative approach.
The study's termination due to barriers to enrollment is relevant context, but it is not an endpoint result. It does not show that the intervention succeeded or failed, and it does not indicate what the response would have been in a larger or differently conducted study. The registry status and stated reason for termination should not be mistaken for statistical evidence about the endpoint.
Overall, the registry provides the question, design classification, endpoint definition, intervention description, and termination reason. It does not provide the outcome evidence needed to quantify the response or assess its precision. The appropriate interpretation is that the study's primary result is unavailable in the registry record, not that the threshold was or was not reached.
13. Why This Trial Matters Statistically
This study illustrates the distinction between a clearly specified endpoint and an interpretable result. The registry gives an operational response rule: ACT greater than 480 seconds at a specified time after the initial rhAT dose. It also states how the response was intended to be summarized. Yet without the endpoint count, denominator, estimate, or confidence interval, readers cannot evaluate the frequency or uncertainty of that response.
It also highlights why enrollment fields and outcome denominators are not interchangeable. The registry lists enrollment as 42, but does not report the number assessed for the primary endpoint. A trial can have an enrollment entry without that entry serving as the denominator for an endpoint analysis. Clear reporting of participants treated, assessed, and analyzed is essential to interpret a proportion.
The design matters as much as the endpoint. A single-group study can describe what was observed after an intervention, but it does not offer a registered control comparison. This limits the kinds of statistical conclusions available, even if a response estimate were posted. Statistical significance or precision in a within-group summary would not create a comparative treatment effect.
Finally, the registry states that the study ended because of barriers to enrollment. That context helps explain why the study did not proceed as intended, but it does not substitute for results or explain the missing analysis details. The record is a useful example of how transparent endpoint definitions, complete outcome reporting, analysis-population information, and careful separation of descriptive findings from comparative claims all contribute to sound 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 principal limitation is the absence of a reported primary endpoint result. The registry does not provide the response percentage, confidence interval, assessed denominator, or number meeting the ACT threshold. This prevents evaluation of both the observed response and its precision.
The enrollment field lists 42, while the number actually enrolled, treated, and assessed is not reported in the registry record. The stated termination reason was barriers to enrollment, but the record does not quantify the effect of those barriers on recruitment or endpoint availability. It is not possible to determine from the posted information whether the endpoint data were unavailable, incomplete, or simply not entered.
The single-group design has no registered comparator, and masking is listed as none. The study therefore cannot provide a direct controlled estimate of a treatment difference. The record also does not report the eligibility criteria in detail, participant characteristics, treatment adherence, the frequency of additional dosing, or the statistical analysis method. These details would be relevant to understanding who contributed to the endpoint and how the response was evaluated.
Analysis-population definitions, missing-data procedures, multiplicity handling, interim analyses, and the statistical analysis plan are not reported in the registry record. The safety reporting lists small at-risk counts without explaining their relationship to enrollment or the safety population. Deaths are not reported, and no serious-event terms are listed; neither entry establishes complete safety ascertainment.
These limitations are specific to the available registry information. They do not establish what happened to participants or what analyses may have been conducted outside the posted record. They do mean that the primary response, its uncertainty, the completeness of follow-up, and the scope of safety reporting cannot be determined from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Response of Recombinant Antithrombin in Heparin Resistant Patients Undergoing Cardiac Surgery — NCT01547728.
- Registry record last updated 2015-07-15; status last verified 2015-07.
- Results first posted 2015-07-15.
- 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
NCT01547728 is a phase 4, single-group study sponsored by Mayo Clinic, registered to evaluate recombinant human antithrombin in heparin-resistant patients scheduled for cardiac surgery. The intervention description specifies an initial intravenous bolus of 500 units and a possible additional bolus of 500 units if heparin resistance remained.
The primary endpoint was the percentage with ACT greater than 480 seconds 3 minutes after the initial dose, with a planned point estimate and 95% confidence interval. The registry lists enrollment as 42, but the actual number enrolled, assessed, or analyzed is not reported. The study is terminated because of barriers to enrollment. The primary endpoint result and analysis details are not reported in the registry record.