Oral Anticoagulation Therapy Pilot Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Anticoagulation Therapy Pilot Study (NCT01959425), a randomized phase 4 study. The primary outcome is Number of Participants With Occurrence of Any Major Thromboembolic Event.

2. Clinical Question

The registry describes the study objective as determining the safety of stopping oral anticoagulation therapy in high-risk patients after successful ablation and a period without atrial fibrillation recurrence. This is a comparative question about the frequency of a defined set of serious outcomes during follow-up. It is not a general question about every possible benefit or harm of either treatment strategy.

The primary outcome combines events of different kinds: major thromboembolic events and major bleeding. A combined outcome can capture more than one clinically important type of event, but its overall count does not show which component occurred. In the posted primary results, neither group has a participant counted with the composite outcome. That observed count is the central result, while the study size and the absence of reported uncertainty estimates for this primary result limit how precisely it can answer the comparative question.

3. Trial Design

The registry identifies this as a phase 4, randomized, open-label, parallel-group study. Participants were assigned to either an Off OAT Group (Test), in which oral anticoagulation therapy was discontinued, or an On OAT Group (Control), in which therapy was continued. Masking is listed as none. The registry enrollment is 80, while the posted primary outcome summaries give group denominators of 32 and 31.

The study concerns patients with paroxysmal atrial fibrillation and associated high-risk factors for embolic events after successful cardiac ablation. The brief study description specifies that participants were to remain free of atrial fibrillation recurrence for 3 months after ablation. The primary evaluation period is 12 months. The registry does not report more detail about how successful ablation, high risk, or recurrence-free status were assessed.

The study start date is 2013-04-17, and the primary completion date is 2019-10-07. Its status is terminated. The reason for termination and whether termination affected planned enrollment or follow-up are not reported in the registry record. The registry lists eight outcome measures, including the primary composite and secondary outcomes concerning bleeding, hospitalization, mortality, quality of life, recurrence, and repeat ablation. These features place the findings in the context of a small pilot comparison rather than a definitive estimate of uncommon outcomes.

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: This was a prospective, multicenter, randomized, controlled, two arm, 1:1 design. Enrolled subjects N=80 (subjects signed informed consent). 63 subjects underwent study procedures, 17 subjects were excluded prior to randomization. According to protocol, enrolled subjects = subjects who sign the study's informed consent form.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Occurrence of Any Major Thromboembolic Event, measured over 12 months.

The primary endpoint is the number of participants with any major thromboembolic event or major hemorrhagic complication during the 12-month evaluation period. The thromboembolic component includes stroke—ischemic, hemorrhagic, or cryptogenic—defined in the registry as an acute focal neurologic deficit of presumed vascular origin lasting at least 24 hours or resulting in death. The other component is major bleeding.

Combining these events gives a single outcome that reflects more than one important potential consequence during follow-up. The count is intended to capture participants experiencing either component, rather than to count the number of events within each participant. Because it is a composite, an overall count alone cannot indicate which component would account for any observed events or whether components followed different patterns.

The posted results report zero participants with the primary outcome in each group. The registry does not provide a confidence interval for the group counts or a reported analysis for this endpoint. Thus, the posted counts describe what was recorded in the analyzed groups, but do not by themselves establish that the underlying event risks are equal. The endpoint is useful for organizing the comparison, while its interpretation depends on the amount of information in the study and the completeness of the reported analysis.

7. Results Posted in the Registry

• Off OAT Group (Test): 0.0% (0/32) versus 0.0% (0/31) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Minor Bleeds

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Off OAT Group (Test): 0.0% (0/32) versus 3.2% (1/31) on control; risk difference -3.2 percentage points (95% CI -9.4 to 3.0); unadjusted two-proportion z-test p = 0.306.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Off OAT Group (Test) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants Hospitalized With Any Thromboembolic or Major Hemorrhagic Event

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Off OAT Group (Test): 3.1% (1/32) versus 0.0% (0/31) on control; risk difference 3.1 percentage points (95% CI -2.9 to 9.2); unadjusted two-proportion z-test p = 0.321.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Off OAT Group (Test) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Atrial Fibrillation Recurrence

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Off OAT Group (Test): 18.8% (6/32) versus 12.9% (4/31) on control; risk difference 5.8 percentage points (95% CI -12.1 to 23.8), risk ratio 1.45 (0.45–4.66); unadjusted two-proportion z-test p = 0.525.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Off OAT Group (Test) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover different aspects of follow-up: minor bleeding, hospitalization for thromboembolic or major hemorrhagic events, death, quality of life, atrial fibrillation recurrence, and repeat ablation. These measures are related to the study's broader safety and follow-up context, but they are not interchangeable with the primary composite endpoint. A change in a quality-of-life score or recurrence measure, for example, would not directly answer the primary question about major thromboembolic or major hemorrhagic events.

The numerical secondary comparisons that are posted have mixed directions rather than a consistent pattern favoring one group. Their risk-difference confidence intervals include zero, and the unadjusted p-values are 0.306, 0.321, and 0.525. The registry does not provide numerical results for every listed secondary outcome. For outcomes without posted numerical results, results are not reported in the registry record.

These secondary findings do not overturn or confirm the primary result. The primary outcome had no observed events in either group, while secondary outcomes measure separate outcomes and include their own uncertainty. Findings from different measures may vary without contradiction because their definitions, event frequencies, and sources of measurement differ.

There are multiple secondary outcomes, and the registry does not report a multiplicity adjustment or a hierarchy that would identify which comparisons should be treated as confirmatory. In general, when many outcomes are examined, isolated nominal patterns can occur by chance. Unadjusted secondary results therefore carry less weight than a prespecified, appropriately analyzed primary outcome. Here, the record's lack of detailed analysis methods makes it especially important to treat secondary comparisons as descriptive rather than definitive evidence.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Minor Bleeds
• Percentage of Participants Hospitalized With Any Thromboembolic or Major Hemorrhagic Event
• Percentage of Expired Participants
• Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS)
• Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS)
• Percentage of Participants With Atrial Fibrillation Recurrence
• Percentage of Participants With Repeat Ablation

9. Statistical Interpretation

10. Statistical Methods Explained

Interpreting a small randomized comparison requires separating the observed counts from what those counts can establish about event risks. The registry identifies the design as randomized and parallel, with no masking. It posts group counts and some secondary comparisons, but detailed statistical methods for the primary analysis are not reported in the registry record.

What does a risk difference describe?

A risk difference expresses the difference between the proportion of participants with an event in one group and the proportion in the other group. A value of zero describes equal observed proportions. It is an absolute comparison, so its interpretation remains tied to the event definition and follow-up period. For the primary endpoint, the posted summaries report zero events in both groups and a risk difference of 0.0. The registry does not report a sampling-based confidence interval or p-value for this primary comparison.

A risk difference can be easier to interpret than a relative measure when event counts are very small, because it describes an absolute contrast. But any estimate based on few or no events is sensitive to the limited information in the data. A zero observed difference does not mean that every possible difference in the underlying population has been ruled out.

What does a confidence interval contribute?

In general, a confidence interval is a range produced by a statistical procedure to represent uncertainty around an estimated quantity. Its width reflects both the observed data and the method used to calculate it. A confidence interval that includes zero for a risk difference is compatible, under that method, with no difference as well as with differences in either direction represented by the interval. It does not assign a probability to the true value, and it does not establish that all values within the interval are equally plausible.

The secondary comparisons include 95% confidence intervals for risk differences. Those intervals include zero. Their breadth indicates that the comparisons do not pin down a narrow range of plausible absolute differences. The registry does not provide the corresponding confidence interval method, so it is not possible to assess the assumptions behind those limits from the record alone.

How should p-values be read?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The secondary comparisons have unadjusted p-values of 0.306, 0.321, and 0.525. In the absence of a reported analysis plan, those values should be treated as unadjusted summaries rather than as a complete account of the evidence.

Unadjusted comparisons do not account for the fact that several outcomes may be examined. When multiple comparisons are made, the chance of seeing an apparently notable result somewhere among them can increase. The registry does not report a multiplicity procedure or a prespecified hierarchy for the secondary outcomes. This is one reason to give secondary findings less weight than a clearly specified primary analysis.

Why does randomization matter, and what does it not resolve?

In general, random allocation is intended to make treatment groups comparable, on average, with respect to characteristics known and unknown at assignment. It supports a causal comparison when allocation is implemented as planned and analysis follows an appropriate strategy. The registry identifies the study as randomized, but does not report the sequence-generation method, allocation concealment, or analysis population. Those details are not reported in the registry record, so the practical protections around assignment cannot be assessed from this information.

Open-label allocation means participants and study personnel were not masked to group assignment. That fact does not itself invalidate an outcome, but it can matter for outcomes involving participant reports, care decisions, or assessment. The registry does not report whether outcome assessment was blinded. The primary endpoint includes defined events, but the record does not explain how events were adjudicated.

What does the planning illustration mean?

The recurrence comparison includes a planning illustration based on fractions of its observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It lists participants per arm for 80% and 90% power under those scenarios. These are planning illustrations computed from the observed effect, not the trial's own design justification and not observed power. The registry does not report the original sample-size justification, target event rate, or assumptions used to plan enrollment.

In general, a planning calculation estimates how many participants might be needed to detect a chosen effect under stated assumptions. If the assumed effect is smaller, more participants are generally required to distinguish it from random variation using the same design and error criteria. Such calculations depend on their assumptions and do not guarantee a future result. They should not be confused with the observed precision of this pilot study, nor interpreted as evidence that the trial was adequately powered for its primary endpoint.

The record does not report interim analyses, a detailed statistical analysis plan, methods for missing outcomes, or a defined analysis population. These omissions constrain any attempt to reconstruct the intended statistical approach. The posted counts and secondary comparisons remain useful descriptions, but the underlying methods cannot be fully evaluated from the registry record.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data identify an estimate, not whether the estimate points in a favorable or unfavorable direction. The primary result records zero participants with the composite endpoint in each group, with denominators of 32 and 31. Although the posted risk difference is 0.0 and its listed limits are also 0.0, the registry does not identify a primary confidence-interval method or report a sampling-based interval for the primary event risk. Those posted limits should not be taken as evidence that the underlying risks are known without uncertainty.

For the secondary risk-difference comparisons, the reported 95% confidence intervals include zero and extend in both directions. In general, an interval spanning zero means that the data and method do not distinguish a positive difference from a negative difference at the interval's stated confidence level. The intervals also show that the estimates are not precise enough to confine the possible difference to a narrow range. The exact limits are reported with the corresponding outcomes; their interpretation depends on the specific event and the method used to calculate them.

Rare outcomes are particularly difficult to estimate precisely in small groups. When there are few events, adding or removing a small number of observed events can materially change the estimated proportion. When neither group records an event, the observed difference is zero, but the data still contain limited information about how often the event might occur in a broader population. The registry does not report a primary uncertainty interval that would quantify that limitation.

Confidence intervals are not guarantees about future study results, and they do not resolve limitations such as missing outcome information, incomplete follow-up, or a change in the population of interest. Those details are not reported in the registry record. Taken together, the posted results support a clear statement about the observed primary counts, but not a precise estimate of the comparative underlying risk.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, but does not report a strategy for controlling multiplicity. In general, multiplicity arises when statistical conclusions are drawn from several tests or outcomes. If each comparison is treated as an independent opportunity to find a difference, the chance of at least one misleadingly small p-value can increase. A prespecified hierarchy, adjustment procedure, or clear designation of exploratory outcomes can help explain how multiple results should be interpreted. None of these details is reported in the registry record.

The available secondary p-values are unadjusted. They should not be treated as though they account for all the outcomes examined. This does not make the observed data meaningless; it means that the secondary comparisons are better read as descriptive signals with uncertain reliability than as separate confirmatory findings. The registry does not report which outcomes, time points, or comparisons were selected in advance for formal testing.

Missing-data methods and analysis populations are also not reported in the registry record. The registry enrollment is 80, while the posted primary group denominators are 32 and 31. Without participant-flow information, it is not possible to determine from the record why these denominators differ from enrollment, which participants were included in each analysis, or whether any outcomes were unavailable. No reason should be inferred from the counts alone.

The record also does not report whether the primary analysis followed an intention-to-treat approach, whether participants were analyzed according to assigned group, or how adherence and discontinuation were handled. These choices can affect interpretation in a randomized study, particularly when the intervention involves stopping or continuing a therapy. Interim analyses, stopping rules, and a detailed statistical analysis plan are likewise not reported in the registry record. Their absence from the record limits assessment of whether the reported summaries follow a prespecified analysis strategy.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (3.2%), myocardial infarction (3.2%), cholecystitis acute (3.1%), pneumonia (3.1%), sepsis (3.1%).

The adverse-event summaries list serious adverse events in 6 of 32 participants in the Off OAT Group (Test) and 2 of 31 participants in the On OAT Group (Control). Other adverse events are listed for 0 of 32 and 4 of 31 participants, respectively. Deaths are listed as 0 in both groups. These are descriptive counts in the registry and should not be conflated with the primary endpoint, which is specifically the composite of major thromboembolic events and major hemorrhagic complications during the 12-month evaluation period.

The registry also lists serious-event terms and percentages, including Atrial Fibrillation and Myocardial infarction at 3.2%, and Cholecystitis acute, Pneumonia, Sepsis, and Arterial bypass thrombosis at 3.1%. The record does not give enough context in these term listings to establish how the percentages relate to group-specific risks or whether terms refer to unique participants or events. They should be read as reported listings, not as comparative estimates.

Counts alone do not establish that an event was caused by a treatment strategy. The record does not report detailed event timing, adjudication, severity grading beyond the serious-event classification, or causal attribution. These summaries provide safety context but do not replace the primary outcome analysis or support a causal conclusion.

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

The posted primary result means that no participant in either reported group was recorded as experiencing the defined composite endpoint during the 12-month evaluation period. This is a statement about the observed data and the outcome definition in the registry. It is not proof that the underlying event risks are identical, and it does not show that either strategy has no risk.

The trial was randomized, which is a useful design feature for a comparative question, but interpretation also depends on the enrollment, follow-up, analysis population, outcome ascertainment, and statistical plan. The registry provides limited detail about these matters. It identifies the study as terminated, but does not report why it ended or how that status affected the results. The posted denominators are smaller than the registry enrollment, and the record does not explain the participant flow that led to them.

The secondary outcomes add descriptive information about bleeding, hospitalization, recurrence, and other aspects of follow-up. Their mixed numerical directions and confidence intervals that include zero do not establish a clear comparative pattern. Because the p-values are unadjusted and the registry does not report a multiplicity plan, these results should not be interpreted as definitive evidence for separate outcome claims.

The primary result also cannot be generalized automatically beyond the population described: high-risk patients with atrial fibrillation after successful ablation who remained recurrence-free for 3 months. The registry does not report enough detail to define how closely a particular patient or clinical setting matches that population. The findings do not answer every question about the treatment strategies, all potential outcomes, or longer follow-up beyond the stated evaluation period.

In statistical terms, the record supports a narrow descriptive conclusion about the recorded primary event counts. It does not establish equivalence, non-inferiority, or a causal safety difference, because those conclusions require prespecified criteria and adequate precision that are not documented in the registry record. The study is best understood as a small pilot comparison with limited ability to resolve uncommon events.

15. Why This Trial Matters Statistically

This trial illustrates a central challenge in clinical biostatistics: a randomized design can address a comparative question, yet rare outcomes and small groups may leave the estimate highly uncertain. The primary endpoint was designed to capture major thromboembolic and major hemorrhagic events over 12 months. The absence of recorded events in both groups is an important description of the observed participants, but it cannot by itself distinguish between genuinely similar risks and a lack of information to detect a difference.

The comparison also demonstrates why an effect estimate needs to be considered alongside its precision and the analysis plan. A risk difference of 0.0 accurately describes the posted primary comparison, but the registry does not provide a primary uncertainty interval that allows readers to assess the range of plausible differences. For the secondary outcomes, the reported intervals span zero, and the unadjusted p-values do not supply a substitute for a prespecified multiplicity strategy.

Another statistical issue is the difference between planning illustrations and trial design justification. The recurrence outcome includes sample-size illustrations based on fractions of an observed effect. Such calculations can help show how assumed effects relate to required study size, but they are not the original sample-size rationale and are not observed power. The registry does not report the trial's own sample-size assumptions or justification.

Finally, the record highlights the importance of reporting participant flow, analysis populations, missing-data methods, outcome adjudication, and planned analyses. Without those details, readers cannot fully evaluate why the posted denominators differ from enrollment or how the results were generated. Transparent reporting of these elements is essential for distinguishing a clear observed count from a strong and precise comparative conclusion.

16. 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.

Several limitations specific to this study constrain interpretation. First, the registry enrollment is 80, while the posted primary group denominators are 32 and 31. The record does not provide a participant-flow account or explain the difference, so the extent and reasons for exclusions, incomplete follow-up, or unavailable outcomes cannot be assessed.

Second, the study is marked terminated, but the reason for termination is not reported in the registry record. It is also not reported whether termination changed enrollment targets, follow-up, or planned analyses. This missing context makes it difficult to judge how closely the final results reflect the intended study design.

Third, the primary endpoint concerns events that may be uncommon, and no events were recorded in either posted group. The record does not report a primary confidence interval that quantifies uncertainty in the underlying event risks, nor does it provide a primary p-value or detailed analysis method. The zero counts therefore have limited ability to rule out meaningful differences.

Fourth, the registry does not report the statistical analysis plan, the sample-size justification, analysis populations, missing-data methods, interim analyses, or outcome adjudication procedures. It also does not report whether event assessment was blinded. These gaps prevent full evaluation of analytic choices and potential sources of bias.

Finally, the secondary results are unadjusted, and no multiplicity strategy is reported. Numerical results are not available for every listed secondary outcome. These limitations mean that the record offers useful descriptive observations, but only a partial account of the trial's planned and executed statistical analysis.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Oral Anticoagulation Therapy Pilot Study — NCT01959425.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2020-12-17.
• 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.

20. Record Summary

NCT01959425 is a phase 4 randomized, open-label, parallel-group study of discontinuing versus continuing oral anticoagulation therapy after successful cardiac ablation in high-risk patients with atrial fibrillation. The registry lists an enrollment of 80, a start date of 2013-04-17, a primary completion date of 2019-10-07, and a terminated status.

The primary outcome was the number of participants with a major thromboembolic event or major hemorrhagic complication during 12 months. The posted results report zero participants with this outcome in each group, with denominators of 32 and 31. The registry does not report a primary uncertainty interval or detailed primary analysis method.

Secondary outcomes cover bleeding, hospitalization, death, quality of life, recurrence, and repeat ablation. The available numerical secondary comparisons are unadjusted and have confidence intervals that include zero. Reasons for termination, participant flow, missing-data methods, analysis populations, multiplicity procedures, and the original sample-size justification are not reported in the registry record.