RE-DEEM Dose Finding Study for Dabigatran Etexilate in Patients With Acute Coronary Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RE-DEEM Dose Finding Study for Dabigatran Etexilate in Patients With Acute Coronary Syndrome (NCT00621855), a randomized phase 2 study. The primary outcome is Number of Participants Displaying the Composite of Major and Clinically Relevant Minor Bleeding Events During Total Observation Time.

2. Clinical Question

RE-DEEM was a phase 2 dose-finding study. Its stated purpose was to evaluate safety and indicators of efficacy for up to four dabigatran doses compared with placebo in this clinical setting. That purpose is broader than the primary endpoint alone: the registry also names cardiovascular and laboratory outcomes, including D-dimer measures. The registry record does not report results for those outcomes in the information.

3. Trial Design

RE-DEEM (NCT00621855) is recorded as a completed, randomized, double-blind, parallel-group, placebo-controlled study. It was a phase 2 dose-finding trial sponsored by Boehringer Ingelheim. The registry lists enrollment of 1878 participants, a start date of 2008-03, and primary completion in 2009-10. These details describe the registered trial; they do not by themselves indicate how many participants contributed data to any particular endpoint.

The comparison involved matched placebo and four twice-daily dabigatran etexilate regimens: 50mg, 75mg, 110mg, and 150mg. The arm descriptions specify altered doses for participants with moderate renal impairment in three of the higher-dose groups: 50mg twice daily in the 75mg group, 75mg twice daily in the 110mg group, and 110mg twice daily in the 150mg group. The description for the 50mg group does not state a similar adjustment. The registry record does not report the randomization ratio, allocation concealment procedures, or additional details about how masking was maintained.

The trial examined dabigatran as an addition to dual antiplatelet treatment, described as aspirin and clopidogrel, in patients with a myocardial infarction as the index event and high risk for further ischaemic cardiovascular events. The listed observation period for the primary endpoint was the six month treatment period plus two week post-treatment follow-up. Secondary outcomes include a composite of cardiovascular death with non-fatal myocardial infarction and non-haemorrhagic stroke, all-cause death, severe recurrent ischaemia, individual cardiovascular events, and D-dimer measures. A bleeding outcome during total observation time is also listed among the secondary outcomes.

The available registry description does not include the trial protocol or a full statistical analysis plan. Details such as the planned allocation proportions, stratification factors, or how dose groups were intended to be compared are not reported in the registry record. The randomized and parallel design supports comparisons between assigned groups in principle, but interpretation of actual comparisons requires the endpoint results and the analysis methods used.

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: Patients receiving aspirin and clopidogrel at randomisation were included. They also had at least 1 additional risk factor (for e.g. age ≥65 years, diabetes previous myocardial infarction, peripheral arterial disease). Moderate renal impairment at screening resulted in dose adjustment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treated set - The treated set includes all patients who received at least one dose of study medication.

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 Number of Participants Displaying the Composite of Major and Clinically Relevant Minor Bleeding Events During Total Observation Time, measured over 6 month treatment period + 2 week post treatment follow up.

The primary endpoint counts treated participants who experienced a composite of major and clinically relevant minor bleeding events during the six month treatment period plus two week post-treatment follow-up. It is a participant-level binary outcome: a participant either met the composite endpoint or did not, according to the registry definition. The stated analysis population is the treated set, defined as participants who received at least one dose of study medication.

Major bleeding was defined using the International Society on Thrombosis and Haemostasis definition. A bleed qualified as major if it was fatal; involved symptomatic bleeding in a critical area or organ, including intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular bleeding with compartment syndrome; caused a haemoglobin fall of 2 g/dL (1.24 mmol/L) or more; or led to transfusion of 2 units or more of whole blood or red cells.

Non-major bleeding events were classified as minor. Clinically relevant minor bleeding was defined as an acute or subacute clinically overt bleed that did not meet the major-bleed criteria but led to hospital admission, physician-guided medical or surgical treatment, or a change in antithrombotic therapy, including interruption or discontinuation of study drug. Minor bleeds not meeting those clinical relevance criteria were not part of this primary composite.

Combining major and clinically relevant minor events gives the endpoint a safety focus while including events that may require medical attention even when they are not classified as major. The registry record does not report the endpoint event counts or comparative results, so the frequency and precision of this outcome cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main registered outcome is binary at the participant level: the primary endpoint asks whether a treated participant experienced at least one qualifying major or clinically relevant minor bleeding event within the stated observation period. The registry record defines who qualified for the treated set and describes the event criteria, but does not report an analysis method or primary outcome results. The explanations below describe general statistical concepts rather than methods confirmed to have been used in RE-DEEM.

What does a binary outcome comparison estimate?

For a binary outcome, analysis commonly begins with the number of participants with an event and the number assessed in each group. An event proportion describes how common the outcome was in a group. A comparison may express the absolute difference between group proportions, a relative measure, or both. These measures answer different questions: an absolute difference describes the separation in event frequency, while a relative measure describes how one frequency compares with another. No such estimate for the primary endpoint is reported in the registry record, and no new estimate can be recovered without its event counts.

Randomization can make groups comparable in expectation at the start of a trial, but the way randomized participants are included in an analysis matters. The registered population for the primary endpoint is the treated set, which includes participants who received at least one dose of study medication. This is not enough to determine the complete analysis approach. The registry record does not report whether other populations were analysed or how participants who stopped treatment, missed follow-up, or had uncertain outcome status were handled.

How should uncertainty be understood?

A confidence interval gives a range of values compatible with the data under the specified statistical method. It communicates precision as well as the direction and plausible size of an estimated effect. An estimate without an interval can conceal substantial uncertainty, especially when events are uncommon. The registry record does not report a confidence interval or point estimate for the primary endpoint, so neither the magnitude nor precision of that comparison can be described.

A p-value is one measure of how inconsistent observed data are with a specified null hypothesis, under the assumptions of the test. It does not measure the probability that the null hypothesis is true, and it does not convey the clinical importance of a difference. A p-value for the primary endpoint is not reported in the registry record. Statistical significance, if reported, would need to be interpreted alongside the effect estimate, confidence interval, endpoint definition, and analysis plan.

Why do multiple groups and outcomes matter?

RE-DEEM includes placebo and four dabigatran dose groups, as well as several secondary outcomes. When many comparisons are examined, the chance of at least one apparently unusual result can increase. Statistical approaches to multiplicity may control that issue, for example by adjusting the threshold for interpreting multiple tests or by defining a hierarchy of comparisons in advance. These are general options, not methods confirmed for this trial. The registry record does not report a multiplicity strategy or identify the comparisons treated as primary beyond naming the primary endpoint.

Dose-finding studies may be designed to explore patterns across several dose levels rather than to answer only one pairwise question. However, the registry record does not report the planned dose-response analysis or the intended ordering of dose comparisons. It would therefore be inappropriate to assume that one particular contrast or trend test was specified.

What does over-dispersion mean?

Over-dispersion is a general concern for some count-data models when observed variability exceeds what a model assumes. It matters when the outcome is a count with variation across participants or settings; standard errors from a model that ignores extra variability may be too small. The primary endpoint in RE-DEEM is described as a count of participants with a binary event, not as a repeated event count. The registry record does not identify a model for the primary endpoint, so there is no basis to say whether over-dispersion was assessed or relevant to the sponsor's analysis.

How should planning assumptions be read?

The stated sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is described as targeting a stated fraction of an observed effect. These assumptions do not establish that the trial itself was designed using those inputs, and the registry record does not report the trial's own sample-size justification. Any sample-size illustration is a planning exercise, not observed power. Observed power is not a substitute for the effect estimate and its confidence interval, and no primary endpoint estimate is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

RE-DEEM has five treatment groups and several registered outcomes, including a primary bleeding endpoint, cardiovascular outcomes, and D-dimer measures. Multiple doses and outcomes create more than one possible comparison. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which dose comparisons were intended to support confirmatory conclusions. It also does not state whether secondary outcomes were intended as exploratory or confirmatory. Those details are not reported in the registry record.

The primary endpoint population is identified as the treated set: participants who received at least one dose of study medication. The registry record does not report whether an intention-to-treat population or another analysis population was used for additional analyses. It also does not report the numbers analysed by group for the primary endpoint or how participants with incomplete follow-up, missing outcome assessments, or treatment discontinuation were handled. Missing outcome data can affect an estimate if the participants with unavailable outcomes differ from those with observed outcomes; the extent and handling of any missingness in this trial are not reported in the registry record.

The registry lists two analyses, but does not describe their methods or relationship to the outcomes. The sponsor's statistical analysis plan, including any interim analyses or prespecified sensitivity analyses, is not reported in the registry record. It is therefore not possible to determine which methods were planned in advance, whether any analyses were adjusted for multiplicity, or how robust the reported findings would be to different missing-data assumptions. The absence of those details should not be replaced with assumptions based on common practice.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: angina pectoris (1.3%), unstable angina (1.1%), chest pain (1.1%), non cardiac chest pain (0.7%), pulmonary oedema (0.6%).

The serious adverse event summary lists the following affected-participant counts and numbers at risk: 33 of 369 for 50mg dabigatran etexilate, 31 of 368 for 75mg, 35 of 406 for 110mg, 21 of 347 for 150mg, and 32 of 371 for placebo. These counts should be read as the registry's serious adverse event summary, not as the primary bleeding outcome. They do not identify how many participants had a major or clinically relevant minor bleed under the primary endpoint definition.

The record also lists serious-event terms and percentages: angina pectoris, 1.3%; unstable angina, 1.1%; chest pain, 1.1%; non cardiac chest pain, 0.7%; pulmonary oedema, 0.6%; and dyspnoea, 0.5%. These terms describe the listed serious events; the registry record does not provide their arm-specific distribution or clarify whether a participant could contribute to more than one term. The percentages should not be added together or treated as a treatment-group comparison.

Serious adverse event counts alone do not establish causation or provide a complete safety comparison. The registry record does not report the primary bleeding results, exposure-adjusted rates, detailed event timing, or a statistical comparison for these summary figures. Interpretation should therefore remain limited to the counts and terms recorded, without treating them as evidence for or against a treatment effect.

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

The registry record establishes that RE-DEEM was a randomized, double-blind, placebo-controlled, phase 2 dose-finding trial in patients with a myocardial infarction as the index event and high risk for further ischaemic cardiovascular events. Participants received dual antiplatelet treatment, and the trial compared placebo with four twice-daily dabigatran etexilate dose groups. The primary endpoint was defined as the number of treated participants with a major or clinically relevant minor bleeding event during the six month treatment period plus two week post-treatment follow-up.

What the posted information does not establish is the primary endpoint result. Event counts by group, a treatment effect estimate, a confidence interval, and a primary comparison test are not reported in the registry record. The serious adverse event summary gives counts by group, but those counts are not interchangeable with the defined primary bleeding endpoint. The registry's listed serious-event terms likewise do not supply an arm-level comparison of the primary outcome.

Accordingly, these registry entries do not support a conclusion about whether the bleeding endpoint was more or less frequent in any dabigatran dose group than in placebo, how large any difference might have been, or how precisely it was estimated. They also do not establish the pattern of efficacy outcomes, which are named among the secondary outcomes but whose results are not reported in the registry record.

In general, a randomized design is intended to support comparisons between groups, while confidence intervals and analysis details help readers assess uncertainty. In this case, the missing endpoint counts and comparative analyses prevent that assessment for the primary question. The trial's recorded design and endpoint definition are informative about what was studied, but they are not substitutes for results.

Finally, registry summaries have limits as a source of statistical detail. The analysis plan, missing-data methods, multiplicity approach, and trial-specific sample-size justification are not reported in the registry record. Any conclusions based on the posted information should remain bounded by those omissions and by the distinction between serious adverse events and the primary bleeding composite.

13. Why This Trial Matters Statistically

RE-DEEM raises several statistical issues that are common in dose-finding trials. A design with placebo and four active-dose groups can address questions about safety across a range of doses, but interpretation depends on how the dose comparisons were planned and how uncertainty was reported. The registry record identifies the groups and a primary safety endpoint, yet it does not report the endpoint counts or the comparative estimates needed to evaluate that endpoint.

The distinction between an outcome definition and an outcome result is central. RE-DEEM defines major bleeding and clinically relevant minor bleeding using clinical criteria and specifies a treated-set population. Those details clarify what the primary endpoint was intended to capture. They do not tell the reader how many participants met that definition in each group, or how different the groups were. Without those results, the primary statistical question remains unresolved in the registry record.

The trial also illustrates why safety summaries should be interpreted according to their labels. Serious adverse event counts are important descriptive information, but they are not necessarily counts of the primary bleeding events. Treating different safety endpoints as equivalent would change the question being answered. The listed serious-event terms provide additional context but do not replace arm-specific results for the primary endpoint.

Finally, multiple doses and outcomes make prespecification and multiplicity relevant. The registry record does not describe the testing strategy, planned comparisons, missing-data handling, or sample-size justification. These details affect how readers assess the strength and precision of findings. The statistical lesson is not a conclusion about the treatment, but the need to distinguish trial design, endpoint definition, outcome data, and analysis plan when evaluating a clinical trial.

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 largest limitation for interpreting the primary question is that primary endpoint event counts and comparative results are not reported in the registry record. The endpoint definition and timeframe are available, but not the group-level outcome data, effect estimate, confidence interval, or test result. This prevents assessment of the size and precision of any between-group difference.

The serious adverse event summary is not a substitute for the primary endpoint. Although counts and at-risk numbers are listed for all five groups, the record does not establish that these serious events meet the bleeding criteria used for the primary composite. The serious-event terms and percentages are also not presented by treatment group, and the record does not provide enough detail to reconstruct a comparative safety analysis from them.

Several design and analysis details are absent. The registry record does not report the trial-specific sample-size justification, randomization ratio, allocation concealment, full statistical analysis plan, multiplicity procedure, interim analyses, or handling of missing outcome information. The treated-set definition is given, but group-specific primary analysis populations and follow-up completeness are not reported. The record also does not provide the results for the listed secondary outcomes in the information.

The dose descriptions include adjusted regimens for participants with moderate renal impairment in some groups, but the registry record does not report how many participants received adjusted doses or their endpoint outcomes. Thus, the group labels alone do not show the distribution of actual doses received. These limitations constrain interpretation of the posted information and should not be filled in by assuming customary trial procedures or results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: RE-DEEM Dose Finding Study for Dabigatran Etexilate in Patients With Acute Coronary Syndrome — NCT00621855.
• Registry record last updated 2014-03-12; status last verified 2014-02.
• Results first posted 2011-02-11.
• 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

RE-DEEM (NCT00621855) was a completed phase 2, randomized, double-blind, parallel-group, placebo-controlled dose-finding study sponsored by Boehringer Ingelheim. The registry lists enrollment of 1878 participants, a start date of 2008-03, and primary completion in 2009-10. The study compared matched placebo with twice-daily dabigatran etexilate at 50mg, 75mg, 110mg, and 150mg in patients with a myocardial infarction as the index event who were receiving aspirin and clopidogrel.

The primary endpoint was the number of treated participants with a major or clinically relevant minor bleeding event during the six month treatment period plus two week post-treatment follow-up. The registry record describes its definition and the treated-set population. It does not report the primary endpoint counts or comparative analysis, so the main safety comparison cannot be evaluated from the posted information. Serious adverse event counts are listed by group, but they are distinct from the primary bleeding endpoint. Analysis-plan details, missing-data methods, and multiplicity procedures are not reported in the registry record.