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 Reversal of Dabigatran Anticoagulant Effect With Idarucizumab (NCT02104947), a na phase 3 study. The primary outcome is Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02104947 |
| Phase | Phase 3 |
| Condition | Hemorrhage |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 503 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients treated with dabigatran etexilate who had uncontrolled bleeding or required emergency surgery or procedures. The primary outcome population is identified as the Treated Set, while the endpoint definition further restricts evaluation to patients with a pre-dose coagulation test result above 100% ULN and at least one post-dose test result. The registry record does not report how many patients met that evaluability definition.
Intervention
Patients received idarucizumab by intravenous administration, with the study summary describing a 5.0g dose. The record identifies idarucizumab as the intervention and describes the study as having one treatment without a placebo or comparator.
Comparator
There was no randomized control group or like-for-like comparator. The record describes a single-group case series, with allocation listed as NA and masking listed as none. Group A and Group B appear in the adverse-event information, but they are not identified as treatment and control groups.
Primary question
The primary outcome asks how much dabigatran anticoagulant effect was reversed, using central-laboratory diluted thrombin time (dTT) or ecarin clotting time (ECT) measurements. The registry defines the measure as the maximum reversal observed from the end of the first infusion through 4 hours after the last infusion on Day 1. The numerical result is not reported in the registry record, so the recorded endpoint definition alone cannot establish the observed extent of reversal.
3. Trial Design
This was a Phase III case series with a single-group model. The registry record lists enrollment as 503 and the study status as completed. It identifies Boehringer Ingelheim as sponsor. The recorded study dates are 2014-05-06 for the start and 2016-07-25 for primary completion. These are registry entries; they do not, by themselves, describe when participants entered or completed follow-up.
The intervention was idarucizumab, described as a single treatment without placebo or comparator. The study summary specifies intravenous administration of 5.0g in patients treated with dabigatran etexilate who had uncontrolled bleeding or needed emergency surgery or procedures. Allocation is listed as NA and masking as none. The registry explicitly notes that the groups are not a like-for-like control comparison. Consequently, the design does not provide a randomized treatment contrast.
Two groups are named in the adverse-event information: Idarucizumab (Group A) and Idarucizumab (Group B). The record also assigns some secondary outcomes to a particular group: time to cessation of bleeding is for Group A, while occurrence of major, life-threatening, or fatal bleeding intraoperatively is for Group B. The registry record does not provide further group definitions in the registry record. Group labels should therefore not be interpreted as randomized arms or as evidence of a controlled comparison.
The primary outcome is a laboratory measure of maximum reversal based on dTT or ECT. Secondary outcomes include other coagulation tests, duration of reversal, bleeding-related outcomes, and unbound dabigatran. The registry lists seven outcome measures and zero analysis entries. That listing does not describe the full statistical plan, which 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
| Stage | Idarucizumab (Group A) | Idarucizumab (Group B) |
|---|---|---|
| STARTED | 301 | 202 |
| COMPLETED | 222 | 146 |
| NOT COMPLETED | 79 | 56 |
Reasons for not completing this period:
| Reason | Idarucizumab (Group A) | Idarucizumab (Group B) |
|---|---|---|
| Withdrawal by Subject | 10 | 3 |
| Lost to Follow-up | 4 | 4 |
| Protocol Violation | 6 | 8 |
| Adverse Event | 57 | 38 |
| Other than stated above | 2 | 3 |
Analysis population for the primary outcome, as defined in the registry: Treated Set
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: Treated set: Treated Set is defined as all patients who were administered idarucizumab.
| Characteristic | Unit | Idarucizumab (Group A) | Idarucizumab (Group B) | Total |
|---|---|---|---|---|
| Participants analysed | 301 | 202 | 503 | |
| Age, Continuous | Years | 77.1 (SD 10.4) | 75.9 (SD 10.5) | 76.6 (SD 10.5) |
| Sex: Female, Male: Female | Participants | 129 | 100 | 229 |
| Sex: Female, Male: Male | Participants | 172 | 102 | 274 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT, measured over from the end of the first infusion up to 4 hours after the last infusion on Day 1.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measures the maximum reversal of dabigatran’s anticoagulant effect using central-laboratory diluted thrombin time (dTT) or ecarin clotting time (ECT). Its stated timeframe runs from the end of the first infusion up to 4 hours after the last infusion on Day 1. The registry identifies the summary measure as a median with a 95% confidence interval, expressed as a percentage.
The endpoint definition applies to evaluable patients: participants must have at least one post-dose coagulation test result and a pre-dose result higher than 100% ULN. Reversal is calculated from the change between the pre-dose and post-dose measurement relative to the pre-dose value above 100% ULN. Calculated reversal above 100 is set to 100. The registry record does not report the number of evaluable patients or the numerical median and confidence interval.
In general, a laboratory endpoint can provide a standardized way to describe a biological measurement over a specified period. A maximum summarizes the most extreme observed reversal within that window; it does not describe how long that level persisted or what happened to every participant. Those are distinct questions, reflected in secondary outcomes such as duration of reversal. The endpoint is therefore a measure of laboratory change, not by itself a full account of clinical outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record defines the primary endpoint but does not report its result. It specifies a median and 95% confidence interval for maximum reversal based on central-laboratory dTT or ECT, but gives no numerical estimate, interval limits, or evaluable-patient count. The posted information therefore supports describing what was intended to be measured, not stating the observed magnitude or precision of the primary endpoint.
The study was a single-group case series with no placebo or comparator. In general, an uncontrolled design can describe observations after an intervention, but it cannot separate the intervention’s association with an outcome from changes that might occur over time or other influences. There is no randomized between-group contrast in this record. The registry also cautions that the named groups are not like-for-like control groups. The two group labels in the safety information should not be treated as the treatment and control arms of a comparative trial.
The primary measure is restricted to evaluable patients with a pre-dose result above 100% ULN and at least one post-dose result. This is an endpoint-specific population definition, not necessarily the same as every treated participant. The registry record does not state how many participants were evaluable, how missing laboratory measurements were handled, or whether other analysis populations were used. Without those details, the degree to which the reported endpoint, if available elsewhere, would represent all treated participants cannot be assessed from this record.
The median is the registered summary statistic. In general, a median describes the midpoint of a distribution and does not show the full spread or shape of individual observations. The 95% confidence interval is intended to convey uncertainty around the estimated median; it is not a range containing 95% of individual patient values. Since neither the estimate nor the interval is reported in the registry record, no conclusion about the endpoint’s precision can be made from the listed definition.
Secondary outcomes cover laboratory and clinical topics, including reversal of aPTT and TT, duration of reversal, dabigatran concentration, cessation of bleeding in Group A, and intraoperative bleeding outcomes in Group B. Their inclusion indicates that the study registered more than one outcome of interest, but their numerical results are not reported in the record. The registry lists seven outcome measures and zero analysis entries; it does not provide a detailed account of which analyses were conducted or how results were selected for reporting.
The safety information gives affected-participant counts for serious and other adverse events separately for Group A and Group B, along with several serious-event terms and percentages. These are descriptive safety observations, not a controlled estimate of risk attributable to treatment. The record does not report deaths as a numerical count. It is important not to interpret an unreported death count as zero, or to infer a comparative safety profile from the group labels.
Overall, the posted record documents a completed Phase III single-group study and defines a laboratory reversal endpoint, but does not provide the primary numerical result. It also lacks the comparator and detailed analysis information needed for a controlled treatment-effect interpretation. The evidence described in this record is consequently limited to design details, outcome definitions, and the reported adverse-event information.
9. Statistical Methods Explained
The registry identifies the primary summary as a median with a 95% confidence interval. It names central-laboratory diluted thrombin time (dTT) or ecarin clotting time (ECT) as the basis for determining reversal. The reported endpoint is maximum reversal within a defined post-infusion period, among patients meeting the registry’s evaluability criteria. The registry record does not provide the numerical estimate, confidence interval limits, or the number of evaluable participants.
What does a median describe?
In general, the median is the middle value when observations are ordered. It can describe a typical point in a distribution without being pulled toward unusually high or low values as strongly as a mean can be. A median does not show the distribution’s full shape, the range of individual responses, or how many participants had values near the midpoint. Those features require additional summaries or individual-level displays, which are not reported in the registry record.
What does a 95% confidence interval mean?
In general, a confidence interval expresses uncertainty in an estimate under the statistical method used to construct it. It is not an interval intended to contain 95% of participants’ individual measurements. Its width depends on features of the data and the method. The registry identifies a 95% confidence interval for the median, but does not report its limits or the method used to calculate it. Thus, the precision of the primary estimate cannot be evaluated from the record.
How is reversal defined?
The registry defines reversal using the pre-dose result and post-dose result relative to a 100% ULN reference. The endpoint is calculated as 100 times the difference between the pre-dose value and the post-dose value, divided by the pre-dose value minus 100% ULN. If calculated reversal is greater than 100, it is set to 100. This definition establishes a bounded endpoint and a reference point; it does not provide the observed result. The record requires a pre-dose result higher than 100% ULN and at least one post-dose coagulation test for a participant to be evaluable.
The maximum is selected from measurements in the stated window, beginning at the end of the first infusion and extending up to 4 hours after the last infusion on Day 1. In general, a maximum captures the most pronounced value recorded in a window, rather than a typical value across all time points. It does not by itself describe duration, consistency across participants, or later measurements. Duration of reversal is separately listed as a secondary outcome, but its numerical result is not reported in the registry record.
Why do the analysis population and missing measurements matter?
The primary population is named as the Treated Set, while the endpoint definition limits calculation to evaluable patients with the required test results. In general, an analysis that uses only participants with sufficient measurements can differ from one that includes all treated participants, particularly if measurement availability is related to participant condition or study procedures. The registry record does not report the count of evaluable participants, reasons for missing tests, or methods for handling missing values. It is therefore not possible to assess the impact of missing laboratory data on the primary estimate.
The record lists zero analysis entries. This is a statement about the registry’s analysis listings, not proof that no statistical analyses were performed. The statistical methods used for the primary confidence interval, any supporting analyses, and any sensitivity analyses are not reported in the registry record. A statistical analysis plan, interim analyses, and a sample-size justification are also not reported in the registry record.
What can a single-group design estimate?
In general, a single-group study can describe measurements observed among participants who receive an intervention. Without a concurrent comparator, it cannot directly estimate the difference between outcomes under the intervention and outcomes under an alternative. Changes from baseline may be informative descriptions, but they do not remove the limitations of lacking a randomized control group. The registry identifies the study as a single-group case series and explicitly warns that the groups are not like-for-like control comparisons.
The registry lists seven outcome measures, including aPTT and TT reversal, duration of reversal, dTT or ECT measurements after the first vial and before the second vial, unbound dabigatran, and selected bleeding-related outcomes. In general, having multiple outcomes raises questions about which results were primary, how analyses were planned, and how chance findings were considered. The record identifies the primary outcome and lists secondary outcomes, but detailed multiplicity procedures and analysis methods are not reported.
The adverse-event information is also descriptive. In general, event counts and percentages can characterize what was recorded in a study group, but interpretation depends on event definitions, observation periods, denominators, and whether participants could contribute more than one event. The available registry record reports participant counts affected for serious and other adverse events and lists selected serious-event terms with percentages. It does not provide enough detail to turn those summaries into a comparative safety estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures, including the primary laboratory endpoint and secondary laboratory and clinical outcomes. It lists zero analysis entries. The record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical plan describing how multiple outcomes were to be interpreted. In general, examining multiple outcomes can increase the chance that at least one result appears notable by chance; a prespecified analysis strategy can clarify how that issue is handled. The record does not state whether such procedures were used.
The primary endpoint is defined for evaluable patients: those with at least one post-dose coagulation test and a pre-dose result higher than 100% ULN. The population field identifies the Treated Set, but the record does not give the number meeting the endpoint-specific evaluability definition. It also does not report how many measurements were missing, why they were missing, or how missing measurements were handled. Consequently, the relationship between the treated population and the population contributing to the primary endpoint cannot be quantified.
In general, missing outcome data can affect both the amount of information available and the interpretation of an estimate, especially if missingness is related to outcomes or participant circumstances. The registry record does not describe assumptions or sensitivity analyses for missing data. Interim analyses and a sample-size justification are also not reported in the registry record. The absence of those details from the registry record should not be read as evidence that no such planning or analyses occurred; it means that their methods cannot be evaluated from the available record.
The registry’s zero analysis entries do not supply a full account of analysis conduct. No numerical primary result or confidence interval is reported, so neither its precision nor consistency with any prespecified analysis can be assessed.
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 |
|---|---|---|---|
| Idarucizumab (Group A) | 160 | 301 | 53.2% |
| Idarucizumab (Group B) | 106 | 202 | 52.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Idarucizumab (Group A) | 139 of 301 |
| Idarucizumab (Group B) | 86 of 202 |
Most frequent serious adverse event terms
| Event term | Organ system | Idarucizumab (Group A) | Idarucizumab (Group B) |
|---|---|---|---|
| Pneumonia | Infections and infestations | 14 of 301 | 7 of 202 |
| Delirium | Psychiatric disorders | 13 of 301 | 8 of 202 |
| Cardiac failure | Cardiac disorders | 11 of 301 | 4 of 202 |
| Septic shock | Infections and infestations | 2 of 301 | 11 of 202 |
| Cardiac failure congestive | Cardiac disorders | 10 of 301 | 2 of 202 |
| Sepsis | Infections and infestations | 7 of 301 | 5 of 202 |
| Acute kidney injury | Renal and urinary disorders | 5 of 301 | 6 of 202 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 7 of 301 | 4 of 202 |
| Cardiac arrest | Cardiac disorders | 1 of 301 | 9 of 202 |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | 7 of 301 | 3 of 202 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Idarucizumab (Group A) | Idarucizumab (Group B) |
|---|---|---|---|
| Constipation | Gastrointestinal disorders | 33 of 301 | 20 of 202 |
| Urinary tract infection | Infections and infestations | 35 of 301 | 17 of 202 |
| Nausea | Gastrointestinal disorders | 21 of 301 | 18 of 202 |
| Headache | Nervous system disorders | 27 of 301 | 6 of 202 |
| Diarrhoea | Gastrointestinal disorders | 14 of 301 | 18 of 202 |
| Hypotension | Vascular disorders | 17 of 301 | 15 of 202 |
| Oedema peripheral | General disorders | 17 of 301 | 14 of 202 |
| Hypokalaemia | Metabolism and nutrition disorders | 23 of 301 | 8 of 202 |
| Pyrexia | General disorders | 23 of 301 | 6 of 202 |
| Anaemia | Blood and lymphatic system disorders | 13 of 301 | 11 of 202 |
Serious events with the highest arm-level rate: septic shock (5.4%), pneumonia (4.7%), cardiac arrest (4.5%), delirium (4.3%), cardiac failure (3.7%).
The registry reports serious adverse events for Idarucizumab (Group A) as 160 affected participants among 301 at risk, and for Idarucizumab (Group B) as 106 among 202 at risk. For other adverse events, it reports 139 affected participants among 301 at risk in Group A and 86 among 202 at risk in Group B. These are group-specific participant counts; the group labels do not establish a randomized comparison.
The listed serious-event terms are septic shock (5.4%), pneumonia (4.7%), cardiac arrest (4.5%), delirium (4.3%), cardiac failure (3.7%), and cardiac failure congestive (3.3%). The registry record does not provide the denominator or further detail needed to interpret these percentages, such as whether they refer to a particular group or observation period. They should be read as listed event summaries, not as treatment-attributable risks or comparative effects.
The deaths field is not populated with a numerical count. Deaths are therefore not reported in the registry record; an unreported count should not be interpreted as zero. In general, adverse-event summaries are descriptive and depend on event definitions, follow-up, and reporting practices. The registry information does not establish that an event was caused by the intervention, and the absence of a control group limits comparative safety interpretation.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase III, single-group case series evaluated intravenous idarucizumab in patients treated with dabigatran who had uncontrolled bleeding or required emergency surgery or procedures. It also specifies a laboratory endpoint intended to quantify maximum reversal of anticoagulant effect using central-laboratory dTT or ECT measurements. These details describe the study’s question and measurement framework.
The record does not report the numerical primary endpoint result, its 95% confidence interval, or the number of evaluable patients. Therefore, the record does not show the observed magnitude of maximum reversal or how precisely it was estimated. The endpoint definition alone is not an outcome result. The registry also lists secondary outcomes, but their numerical results are not reported in the record.
The design has no randomized comparator. In general, results observed in a single group cannot establish how outcomes would have differed under an alternative treatment or no intervention. The registry explicitly cautions that the named groups are not like-for-like control groups. The adverse-event figures can be read as reported descriptive counts, but not as a controlled comparison or proof that events were caused by treatment.
The primary endpoint has a specific evaluability rule and measurement window. It summarizes a maximum within that window and uses a capped percentage definition. It does not, on its own, describe the duration of reversal, all clinical outcomes, or every participant’s response. Those questions require other results and additional details that are not reported in the registry record.
Accordingly, the posted record supports a description of the trial design, endpoint definition, and selected adverse-event information. It does not support a numerical statement about the primary effect or a comparative conclusion about treatment benefit or harm. The missing result and analysis details leave important questions about precision, missing data, and interpretation unresolved in this registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between a clearly defined endpoint and a reported endpoint result. The registry specifies the assay basis, summary measure, timeframe, and evaluability rule for maximum reversal. Those elements are essential to understanding what an estimate would represent. But the numerical estimate and confidence interval are not reported in the registry record, so the endpoint’s magnitude and precision cannot be assessed from the listed information.
The single-group case-series design also shapes what statistical conclusions are possible. In general, a laboratory change after an intervention can be described within the observed group, but without a randomized comparator it does not quantify a treatment contrast. The registry’s warning that the named groups are not like-for-like controls is important when reading the separate safety counts. Group labels alone do not create a controlled comparison.
The endpoint’s evaluability criteria illustrate how analysis populations can differ from enrollment. Only participants meeting the stated pre-dose and post-dose measurement conditions contribute to the defined primary endpoint. The registry does not report how many participants were evaluable, so the coverage of the endpoint relative to the treated population remains unclear.
The record also lists several secondary outcomes and adverse-event summaries, while providing no detailed statistical analysis plan in the information. In general, multiple outcomes and incomplete reporting of analysis methods make it harder to understand how uncertainty and selection among results were handled. The registry’s zero analysis entries should not be mistaken for evidence that no analyses occurred; they indicate that analysis details are not listed in that registry field.
These features make the record useful for understanding the study’s measurement and design while underscoring the limits of what can be inferred from the registered information. A result definition, a study completion status, and descriptive safety counts do not substitute for the primary estimate, its uncertainty, and a suitable comparative design.
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 most immediate limitation in the registry record is the absence of a numerical primary outcome result. Although the endpoint is defined as maximum reversal based on dTT or ECT and is specified as a median with a 95% confidence interval, neither the estimate nor interval limits are reported. The number of participants evaluable for this endpoint is also not reported.
The study is identified as a single-group case series, with no placebo or comparator and no masking. The registry cautions that the named groups are not like-for-like control comparisons. This design limits interpretation to descriptions of observations in the study groups and does not provide a randomized estimate of a difference between treatment strategies.
The endpoint is based on laboratory measurements and applies only to participants meeting the stated evaluability criteria. The record does not explain the amount or reasons for missing laboratory data, how missing values were handled, or whether sensitivity analyses addressed missingness. It also does not report the analysis method used to construct the confidence interval.
The registry lists seven outcome measures but no analysis entries. Detailed methods for multiplicity, interim analyses, and sample-size justification are not reported in the registry record. The adverse-event information includes group-specific counts and selected serious-event percentages, but the registry entries do not provide the context needed for a controlled safety comparison. The deaths field has no numerical value, so deaths are not reported rather than reported as absent.
These limitations concern what can be established from the registry record; they do not establish that additional analyses or information do not exist elsewhere. The record itself does not provide those details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Reversal of Dabigatran Anticoagulant Effect With Idarucizumab — NCT02104947.
- Registry record last updated 2018-01-05; status last verified 2018-01.
- Results first posted 2017-08-18.
- 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
NCT02104947 is a completed Phase III single-group case series sponsored by Boehringer Ingelheim. It evaluated intravenous idarucizumab, described as a 5.0g dose, in patients treated with dabigatran etexilate who had uncontrolled bleeding or required emergency surgery or procedures. The registry lists enrollment as 503 and identifies no placebo or comparator.
The primary outcome is maximum reversal based on central-laboratory dTT or ECT, summarized as a median with a 95% confidence interval over the stated Day 1 timeframe. The registry defines an evaluable patient using pre-dose and post-dose coagulation test requirements, but does not report the evaluable count or the numerical primary result.
Seven outcome measures are listed, with zero analysis entries. Serious and other adverse-event counts are reported for Groups A and B, along with selected serious-event terms. The registry record does not report a numerical death count or detailed statistical methods for missing data, multiplicity, or the primary confidence interval.