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 Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial (NCT06038708), a registered phase not stated study. The primary outcome is Heart Rate [Bpm] at Specific Time-points During Head-up Tilt Test (HUTT) Examination.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06038708 |
| Phase | Phase not stated |
| Condition | Syncope, Syncope, Vasovagal |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Biotronik SE & Co. KG |
| Results posted | Yes |
2. Clinical Question
Population
Patients with reflex syncope and an asystolic response who received a dual-chamber pacemaker with closed loop stimulation (CLS) and participated in the BIOSync trial. The registry lists an enrollment of 20. Additional eligibility details and characteristics of the analyzed population are not reported in the registry record.
Intervention
The study concerns patients with a CLS pacemaker during a head-up tilt test (HUTT). The registry describes assessing hemodynamic parameters and their timing in relation to the onset of CLS pacing. It does not describe a newly assigned intervention or a protocol for changing pacemaker programming.
Comparator
No like-for-like control comparison is described. The registry does not state an allocation method, and the posted information does not establish a randomized comparison. The measurements are described across stages of the HUTT rather than as outcomes for a stated control group.
Primary question
How does heart rate, measured in beats per minute, vary across the HUTT stages, including the pre-syncopal phase and the stage defined by syncope or the lowest systolic blood pressure? The study also aims to explore the timing of hemodynamic changes in relation to CLS pacing onset; the posted primary endpoint is heart rate at specified test stages.
This question is descriptive and physiologic: it concerns the pattern and timing of measurements during a test in a particular patient group. The registry's stated purpose is to add knowledge about mechanisms underlying recurrent syncopal events and pacing programming. That purpose does not, by itself, establish that the study can compare pacing with no pacing, determine the effect of a programming strategy, or establish a clinical benefit. The record does not provide the heart-rate values, their variability, or results of comparisons across stages. Therefore, the direction, size, and precision of any observed changes cannot be assessed from the posted results.
3. Trial Design
The registry identifies a completed study titled “Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial.” The official title uses the name BIO|Sync-HUTT. The listed conditions are syncope and vasovagal syncope. The study is sponsored by Biotronik SE & Co. KG.
The study focuses on HUTT examination in patients who had received a dual-chamber pacemaker with CLS and participated in BIOSync. Its stated purpose is to explore changes in hemodynamic parameters during the test and their timing in relation to CLS pacing onset. The listed enrollment is 20. The record gives a study start date of 2022-09-29, a primary completion date of 2023-05-12, and a status of completed.
The primary outcome is a continuous measure: heart rate in beats per minute, summarized as a mean with standard deviation. Measurement is described at specific time points or stages during HUTT, from baseline through syncope or the lowest systolic blood pressure. The timeframe is from the start to the end of the examination, assessed up to 45 minutes. The record identifies four stages, but does not describe the timing schedule in further detail.
The registry does not state an allocation method or describe a like-for-like control comparison. The posted information therefore supports describing measurements in the stated patient group, not interpreting the study as a randomized treatment comparison. Further design details, including recruitment procedures, protocol specifications, and the analysis population, are 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 | DDD-CLS Patients |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
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 | DDD-CLS Patients |
|---|---|---|
| Participants analysed | 20 | |
| Age, Continuous | years | 68.3 (SD 11.9) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 16 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Italy | Participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Heart Rate [Bpm] at Specific Time-points During Head-up Tilt Test (HUTT) Examination, measured over From the start to the end of the HUTT examination, assessed up to 45 minutes.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | beats per minute |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is heart rate, measured in beats per minute at specific time points or stages during the head-up tilt test. The registry describes a mean as the summary measure and standard deviation as the measure of dispersion. The measurement period begins at the start of the test and continues to its end, assessed up to 45 minutes.
The stages are baseline (Stage 1), the pre-syncopal phase (Stage 2), maximum heart rate or pacing rate (Stage 3), and syncope or the lowest systolic blood pressure (Stage 4). Recording heart rate at these stages can describe how the measure changes over the course of the test and how those measurements relate in time to the physiologic events specified in the endpoint description. This fits the stated aim of exploring hemodynamic changes and their timing in relation to CLS pacing onset.
For a continuous measurement, the mean describes the central value across observations, while the standard deviation describes how dispersed those observations are around the mean. The endpoint description does not give the actual means or standard deviations at any stage. It also does not report stage-specific participant counts, individual measurements, or a statistical test comparing stages. Consequently, the endpoint definition explains what was intended to be measured, but the posted record does not allow the size or precision of the observed heart-rate pattern to be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry specifies a clinically relevant physiologic question: how heart rate varies during HUTT in patients with reflex syncope and an asystolic response who received a CLS pacemaker and participated in BIOSync. It also states an interest in the timing of hemodynamic changes in relation to CLS pacing onset. Those aims describe what the investigators wanted to explore; they are not themselves findings.
The posted record identifies heart rate as the primary outcome and describes its measurement across four stages. However, it does not report the stage-specific heart-rate means or standard deviations. It also reports no statistical analyses. As a result, the record does not show whether heart rate rose, fell, or remained similar across stages, how variable the measurements were, or how precisely any pattern was estimated. There is no reported effect estimate or confidence interval to interpret. The registry record also does not report a p-value for a stage comparison.
Without numerical outcome results, it is not possible to assess the magnitude or consistency of a change, or whether a difference between stages would be large relative to the variability in measurements. A mean alone would not fully describe the distribution of individual measurements; the standard deviation would add information about their spread, but those values are also absent. General statistical interpretation requires both the observed estimate and information about its uncertainty. Neither can be recovered from the endpoint description alone.
The design information also limits causal interpretation. The registry does not state an allocation method and does not describe a like-for-like control comparison. Measurements taken at successive test stages can describe a sequence, but a sequence of measurements is not, by itself, evidence that pacing caused a change. The record does not report a comparison that separates pacing-related changes from other changes occurring during the test.
Any sample-size figures based on an observed effect are planning illustrations rather than observed power. The stated planning assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. These assumptions do not establish that this study used that design or analysis. The registry does not report an observed effect on which to base a substantive interpretation. Overall, the posted information supports describing the study question and endpoint, but not drawing a conclusion about the heart-rate findings or their clinical implications.
9. Statistical Methods Explained
The primary measure is continuous: heart rate in beats per minute. The registry specifies that it is summarized by a mean and standard deviation at defined HUTT stages. These are descriptive statistics. A mean gives a central summary of observed values, while a standard deviation describes their spread around that mean. They are useful together because similar averages can occur with different degrees of variability. The registry describes these summaries as planned, but the actual stage-specific values are not reported in the registry record.
What does a sequence of stage measurements tell us?
Measurements at baseline, during the pre-syncopal phase, at maximum heart rate or pacing rate, and at syncope or the lowest systolic blood pressure can describe how heart rate varies during the examination. A within-test sequence can be informative about timing and patterns. It does not automatically establish that one event caused another. In particular, an observed change around the onset of CLS pacing would need suitable measurements and an analysis that addresses the timing and structure of those observations before a causal interpretation could be made. The registry states an interest in timing, but does not report the detailed method used to analyze it.
Repeated measurements from the same person are generally related: a person's measurements can share characteristics that distinguish them from measurements in other people. General statistical methods for repeated observations account for this dependence when estimating change and uncertainty. Treating all measurements as independent when they are related can make uncertainty appear smaller than it is. This is a general consideration, not a description of an analysis confirmed by the registry. The statistical model or test used for the staged heart-rate measurements is not reported in the registry record.
How should uncertainty be read?
A confidence interval is a range of values compatible with the data and the method used to estimate uncertainty. Its width conveys precision: a wider interval represents less precise estimation than a narrower one. A confidence interval can also help readers judge whether the data are compatible with a range of effects, rather than reducing interpretation to a threshold decision. No confidence intervals or other uncertainty estimates for the heart-rate outcome are reported in the registry record, so the precision of the findings cannot be evaluated.
A p-value, when reported, describes how compatible data are with a specified statistical model and null hypothesis. It is not a measure of the size or clinical importance of a difference. The registry record reports no statistical analyses and no p-values for the primary endpoint. It is therefore not possible to assess statistical evidence for differences between stages. The endpoint description alone does not identify a hypothesis test, adjustment method, or decision threshold.
What do the planning assumptions mean?
The registry's stated sample-size assumptions describe planning illustrations, not the design actually used in this study and not observed power. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of an observed effect. Such calculations can illustrate how planned sample size depends on assumptions about the effect and analysis. They do not show the probability that a completed study has detected an effect, and they do not substitute for reported outcome estimates and uncertainty.
The assumptions also refer to two-arm allocation, while the posted design information does not establish a randomized comparison or a like-for-like control group. Accordingly, the planning setup should not be read as evidence that the clinical study enrolled two allocated arms. The registry does not report a sample-size justification specific to the study, nor does it report an analysis plan explaining how the continuous endpoint was handled.
Finally, the number of outcome measures listed is 14, while the primary endpoint is identified as heart rate at specified HUTT stages. Statistical interpretation would ordinarily distinguish the primary question from additional outcomes and consider how multiple comparisons are handled. The registry does not report the method, if any, used to account for multiple testing. The lack of reported analyses means that no particular statistical procedure should be attributed to this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures and identifies heart rate at specified HUTT stages as the primary outcome. When a study examines multiple outcomes, time points, or comparisons, the chance of finding at least one apparently notable result can increase. Statistical approaches can address that issue, but the appropriate approach depends on the prespecified questions and analysis plan. The registry record does not report whether multiplicity was addressed, what comparisons were planned, or whether any adjustment was used.
The primary endpoint spans four stages of the tilt test. The record does not say whether a single overall comparison, separate stage comparisons, a model of measurements across stages, or another method was intended. No test results, estimates, confidence intervals, or p-values are reported. Consequently, there is no basis for judging how multiple comparisons may have affected interpretation or for distinguishing prespecified analyses from exploratory ones.
Information about missing data is also absent. The registry does not report whether any heart-rate measurements were missing, how missing observations were handled, or whether the analysis used all enrolled participants or a defined subset. Enrollment of 20 does not establish how many participants contributed usable measurements at each test stage. The analysis population and any exclusions are not reported in the registry record.
These omissions matter because missing measurements and analysis choices can affect the estimate and its uncertainty. They do not show that missing data or multiplicity problems occurred; they mean that the posted record does not describe how those issues were handled. The listed outcome count, endpoint definition, and enrollment are not enough to reconstruct the analysis.
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 |
|---|---|---|---|
| DDD-CLS Patients | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DDD-CLS Patients | 0 of 20 |
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 |
|---|---|
| DDD-CLS Patients | 0 of 20 |
For the DDD-CLS Patients group, the registry lists 20 at risk for serious adverse events and 0 serious adverse events. It also lists 20 at risk for other adverse events and 0 other adverse events. Deaths are listed as 0, and no serious adverse event terms are listed.
These figures describe the safety counts recorded in the registry, not a comparison between treatment groups. The posted information does not establish a control group or a comparative safety estimate. A recorded count of 0 means that the registry reports no events in that category; it does not, by itself, establish the absence of risk or characterize safety beyond the record's reporting.
The registry does not provide event definitions, event-specific observation periods, details about how events were collected, or further context for interpreting the at-risk counts. The figures therefore should be read as the recorded counts for the named group, rather than as proof that no adverse events could occur. They also do not provide evidence about differences in safety between CLS pacing and another approach.
12. What the Result Does, and Does Not, Mean
This study is designed to describe heart-rate measurements during HUTT in a specific group: patients with reflex syncope and an asystolic response who received a dual-chamber pacemaker with CLS and participated in BIOSync. Its focus on test stages and the timing of hemodynamic changes corresponds to a physiologic research question. The registry's stated purpose is to add knowledge about mechanisms underlying recurrent syncopal events and optimal pacing programming.
The posted record does not report the primary outcome values or statistical analyses. It therefore cannot establish the direction or size of changes in heart rate, the amount of variability, or the precision of any estimate. Nor can it show whether the timing of pacing onset coincided with a particular pattern in the measurements. Those are questions the study aims to explore, but the endpoint description and study purpose are not outcome results.
The record also does not describe a randomized comparison or a like-for-like control group. The available information consequently cannot identify a causal effect of CLS pacing, compare CLS with another pacing strategy, or establish that a programming approach improves outcomes. Even a pattern across test stages would need to be interpreted in the context of an analysis and design capable of supporting the relevant comparison.
The safety record lists 0 serious adverse events, 0 other adverse events, and 0 deaths in the DDD-CLS Patients group. Those entries describe what is recorded, but do not provide a comparative safety assessment or a complete account of how events were defined and collected.
In short, the registry record clarifies the study population, physiologic aim, and primary measurement. It does not report the results needed to judge the observed heart-rate pattern, its uncertainty, or its clinical significance. Conclusions beyond the study's stated scope are not supported by the posted information.
13. Why This Trial Matters Statistically
This study raises statistical questions that are important when interpreting physiologic measurements collected over time. Heart rate is recorded at stages within a HUTT, with interest in the timing of hemodynamic changes in relation to CLS pacing onset. Such data are not simply a set of unrelated measurements: the sequence and timing are central to the question, and measurements from the same person may be related. Clear reporting of the measurement schedule and analysis is therefore important for understanding what a stage pattern can establish.
The registry identifies a continuous primary outcome and specifies mean and standard deviation summaries. Those details help define the intended measurement, but summaries alone would not answer every question about timing, within-person change, or uncertainty. The analysis method matters, as does reporting the estimates and their precision. In this record, the outcome values and statistical analyses are not reported, so readers cannot evaluate the pattern or its reliability.
The study also illustrates why a stated physiologic aim should be distinguished from a causal comparison. The record does not state an allocation method or describe a like-for-like control comparison. Planning assumptions involving equal allocation between two arms do not establish that the clinical study used such a design. Statistical plans and design descriptions need to be read separately from generic planning calculations.
Finally, the registry lists 14 outcome measures but does not report how multiple outcomes or stage comparisons were handled. The endpoint, analysis population, missing-data handling, and multiplicity approach all affect how results should be interpreted. These details are particularly relevant when a study aims to explore patterns rather than report a single simple contrast. The record identifies the question, but leaves those statistical interpretation details unresolved.
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 direct limitation for interpreting this trial is that the registry record does not report the primary heart-rate results or any statistical analyses. Although the endpoint is defined by stage and summary measure, no stage-specific means, standard deviations, or estimates of uncertainty are available in the record. The magnitude, direction, and precision of the observed pattern therefore cannot be assessed.
Design information is limited for evaluating comparisons. The record does not state an allocation method and does not describe a like-for-like control comparison. It is therefore not possible to use the posted information to assess a comparative effect or attribute any change to CLS pacing. The relationship between test-stage measurements and pacing onset is part of the study's stated aim, but the timing and analysis details are not reported.
The registry lists enrollment of 20, but does not report the number contributing measurements at each stage, the analysis population, or exclusions. Missing-data frequency and handling are not reported. The record also lists 14 outcome measures without describing a multiplicity approach, prespecified comparisons, or how additional outcomes were interpreted.
Further limitations include the absence of detailed eligibility criteria, participant characteristics, test procedures, and statistical methods in the posted information. The safety counts are listed, but event definitions, collection methods, and further observation details are not reported in the registry record. These gaps do not prove that the study lacked appropriate procedures; they constrain what readers can verify and conclude from the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial — NCT06038708.
- Registry record last updated 2025-02-03; status last verified 2024-10.
- Results first posted 2025-02-03.
- 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
The registry describes a completed study of head-up tilt testing in patients with reflex syncope and an asystolic response who received a dual-chamber pacemaker with CLS and participated in BIOSync. Its purpose is to explore hemodynamic changes during the test and their timing in relation to CLS pacing onset. The record lists enrollment of 20 and identifies heart rate in beats per minute at specified HUTT stages as the primary outcome, summarized by mean and standard deviation.
The registry lists a start date of 2022-09-29, a primary completion date of 2023-05-12, and a completed status. It reports 0 serious adverse events, 0 other adverse events, and 0 deaths for the DDD-CLS Patients group. The heart-rate outcome values, statistical analyses, analysis population, missing-data handling, and multiplicity methods are not reported in the registry record. The posted information defines the study question but does not permit assessment of the primary outcome findings.