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 Specialized Pacing for Patients With Congenital Heart Disease (NCT03361189), a randomized phase 2, phase 3 study. The primary outcome is Number of Participants With Blunted or Unchanged Effect of Mental Stress on Heart Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03361189 |
| Phase | Phase 2, Phase 3 |
| Condition | Congenital Heart Disease, Bradycardia Sinus |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, Los Angeles |
| Results posted | Yes |
2. Clinical Question
Population
People with congenital heart disease and sinus bradycardia who had epicardial pacemaker implantation were the intended population. The registry reports enrollment of 4 participants. For the primary outcome, it states that one participant completed autonomic testing.
Intervention
Closed loop stimulation (CLS) is a sensor-based pacing algorithm. The registry describes it as using changes in myocardial systolic impedance to modulate heart rate during physical and emotional stress. In one sequence, participants received CLS-on for 3 months followed by standard rate response for 3 months.
Comparator
The comparator was standard rate response. In the other sequence, participants received standard rate response for 3 months followed by CLS-on for 3 months. The registry describes the study as randomized, double-masked, and crossover.
Primary question
The primary outcome was the number of participants with a blunted or unchanged heart-rate response to mental stress during each intervention. A math test was performed during autonomic testing. The registry does not report a primary-outcome analysis or the result for either pacing condition.
Statistically, the study was intended to compare responses under two pacing conditions within a crossover design. Such a design can allow each participant to contribute observations under both conditions, but the interpretation depends on the recorded outcomes, the sequence and timing of measurements, and how the analysis accounts for within-participant dependence. The registry record does not report enough analysis detail to determine how the intended comparison was estimated.
The record also lists average oxygen consumption during each intervention and quality of life assessed by SF-36 as secondary outcomes. It does not report results or analyses for these outcomes. The central question is therefore clear from the registered outcome description, but the posted record does not provide an estimate of the response under either intervention or a quantified comparison between them.
3. Trial Design
The trial is listed as randomized, double-masked, and crossover, with phase listed as phase 2 and phase 3. The sponsor is the University of California, Los Angeles. The registry records enrollment of 4 and a status of terminated. The recorded start date is 2021-05-09, and the recorded primary completion date is 2021-11-03. The reason for termination is not reported in the registry record.
The crossover structure assigns participants to one of two treatment sequences. In the CLS-On sequence, participants were programmed to CLS-on for 3 months and then standard rate response for 3 months. In the CLS-Off sequence, participants received standard rate response for 3 months and then CLS-on for 3 months. The primary outcome description places autonomic testing at 3 months after the start of each intervention, over a total period of 6 months.
In a crossover trial, treatment condition and period both matter. A within-participant comparison can account for stable differences between participants, while treatment order may help distinguish intervention effects from changes associated with time or sequence. General statistical considerations include whether the first intervention could influence the response during the later intervention, whether period effects are present, and how incomplete participation is handled. The registry record does not report the analysis approach for sequence, period, carryover, or within-participant correlation.
Although the design description indicates two treatment sequences, the registry does not report the sequence allocation counts or a participant flow by sequence. Enrollment should therefore not be read as evidence that all enrolled participants completed both periods or the primary testing. The record specifically states that one participant completed autonomic testing for the primary outcome. Further details about completion, withdrawals, and the analysis population are not reported in the registry record.
The registered secondary outcomes are average oxygen consumption during each intervention and quality of life assessed by SF-36. The record lists 4 outcome measures but no analyses. It does not describe the masking procedures, allocation method, treatment adherence, washout arrangements, or the statistical plan.
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 | CLS-On Followed by CLS-Off | CLS-Off Followed by CLS-On |
|---|---|---|
| STARTED | 2 | 2 |
| Completed Test Period 1 Completed | 1 | 1 |
| Test Period 2 Begun | 1 | 1 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | CLS-On Followed by CLS-Off | CLS-Off Followed by CLS-On |
|---|---|---|
| Received heart transplant | 1 | 0 |
| Pacemake replacement | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: One participant completed autonomic testing
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 | CLS-On Followed by CLS-Off | CLS-Off Followed by CLS-On | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 2 | 4 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 2 | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 2 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Blunted or Unchanged Effect of Mental Stress on Heart Rate, measured over 3 months after the start of each intervention, a total of 6 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with a blunted or unchanged effect of mental stress on heart rate. The registered description says heart rate was assessed during mental stress, with a math test performed during autonomic testing. Measurements were intended for each intervention at 3 months after its start.
This endpoint is a count of participants classified as having a blunted or unchanged response, rather than a continuous summary of heart-rate change. A binary classification can make a clinically framed response easy to describe, but it also depends on how “blunted” and “unchanged” are defined. The thresholds or rules used to classify an individual are not reported in the registry record. The record also does not give the observed count under either intervention.
In general, autonomic responses to a mental stress task can be used to characterize heart-rate modulation under different pacing conditions. For a crossover comparison, the measurements are paired by participant: the response under one intervention is related to that same participant’s response under the other. Analyses should preserve that pairing rather than treat the two conditions as independent groups. The registry record does not report how the endpoint was analyzed or whether the analysis used the paired structure.
The registry states that one participant completed autonomic testing. This indicates that the posted primary-outcome information is limited, but it does not specify the number classified in either category or condition. A primary endpoint definition alone does not establish an intervention effect; an outcome estimate and its uncertainty are needed to describe the observed comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the intended comparison and reports a small enrollment, but it does not post a primary-outcome analysis. The primary outcome is defined as a count of participants with a blunted or unchanged heart-rate response to mental stress during each intervention. The registry states that one participant completed autonomic testing, yet it does not report the corresponding result under CLS or standard rate response. No effect estimate, confidence interval, or statistical test is reported for that endpoint.
Consequently, the record does not quantify how the response differed between the two pacing conditions. It also does not show the precision of such a difference. A confidence interval, in general, describes a range of values compatible with the data and the statistical model; a wide interval would indicate substantial uncertainty. Because no interval or estimate appears in the registry record, the magnitude and precision of the primary comparison cannot be assessed from the posted results.
The design is a randomized crossover, so the intended comparison is not simply a comparison of unrelated groups. A crossover analysis usually accounts for observations made on the same participant under both conditions. However, the registry does not report an analysis method or enough outcome data to determine whether a paired comparison was performed. It does not report treatment sequence or period results, either. These omissions mean that the design can be described, but the analysis cannot be reconstructed from the registry record.
The listed secondary outcomes are average oxygen consumption during each intervention and quality of life assessed by SF-36. The record lists 4 outcome measures overall and 0 analyses. It does not post results for those secondary outcomes. A named outcome or a stated measurement period is not evidence of an observed benefit or harm; the actual results and their uncertainty are needed for interpretation.
The safety entries show 0 serious adverse events and 0 other adverse events in each recorded group, with 0 deaths in each. These are the registry’s group-specific counts. The entries do not establish that adverse events were comprehensively captured for every participant or period, because the record does not explain the safety collection and reporting procedures. The recorded counts should be read as posted registry figures, not as proof that no events occurred outside the reported information.
The registry status is terminated, but the reason for termination is not reported in the registry record. It is not appropriate to infer a reason from the status alone. The available information supports a description of the intended study and the limited posted counts; it does not support a conclusion about the comparative effect of CLS and standard rate response.
9. Statistical Methods Explained
Statistical interpretation starts with the outcome and the design. Here, the primary outcome is a count of participants classified as having a blunted or unchanged response to mental stress, and the design is a randomized crossover. The endpoint description tells the reader what the investigators intended to count; it does not supply the results or the rule used to classify a response. The classification criteria are not reported in the registry record.
What does a crossover comparison require?
In a crossover study, a participant can be measured under both interventions. The two observations from a participant are generally related, because they come from the same person. General statistical practice therefore accounts for within-participant pairing when estimating a treatment contrast. Treating the observations as if they came from unrelated participants can misrepresent uncertainty. The registry record does not report the specific analysis method, so it is not possible to tell how pairing was handled.
Sequence and period are also relevant in crossover studies. Sequence denotes the order in which a participant receives the interventions, while period refers to the stage of the study in which a measurement occurs. A response can vary by period for reasons unrelated to intervention, and an earlier intervention could potentially influence a later measurement. These are general design considerations, not findings about this trial. The registry record does not report whether period or carryover effects were assessed, or whether a washout period was used.
How should a binary endpoint be read?
A binary endpoint sorts an observation into categories, such as whether a participant meets a specified response definition. The primary outcome combines “blunted” and “unchanged” in its title, but the registry does not report the operational definition or threshold for either term. Without that information, readers cannot independently assess how participants were classified. The registry also does not report the count in either intervention condition, so a difference in counts cannot be described.
For a paired binary outcome in a crossover design, the pattern of each participant’s classification across the two conditions can matter. The marginal count in each condition alone may not fully represent the paired comparison; the participant-level transitions between categories can be important. This is a general statistical point. The registry record does not provide such participant-level results or a reported paired analysis.
What do an estimate and its uncertainty contribute?
An effect estimate describes the size and direction of a comparison according to a stated measure. A confidence interval communicates uncertainty around that estimate under the chosen statistical model. A small dataset can yield imprecise estimates, but the degree of imprecision must be assessed from the actual estimate and interval rather than inferred from a design label alone. Neither an effect estimate nor a confidence interval for the primary outcome is reported in the registry record.
A p-value, when reported, addresses how compatible the observed data are with a specified null model; it is not a measure of clinical importance and does not give the probability that a treatment effect is true. No p-value or primary-outcome analysis is reported. There is therefore no reported inferential result to interpret for the primary endpoint.
How should sample-size illustrations be understood?
General sample-size planning asks how many participants would be needed under stated assumptions to detect a specified effect with a chosen error rate and power. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as a stated fraction of an observed effect. These are planning assumptions, not evidence about the effect observed in this trial. Sample-size illustrations are not observed power and do not establish whether the study was adequately powered.
The planning description also distinguishes between participants per arm for ordinary outcomes and total events for time-to-event outcomes. The primary outcome in this record is a participant count, and the registry does not report a single analyzed comparison or an observed effect estimate on which to base a trial-specific interpretation. No numerical planning results are reported in the registry record. They should not be treated as observed outcomes or as a substitute for an analysis.
More generally, statistical methods are most interpretable when the analysis population, outcome definition, model, missing-data approach, and handling of the randomized sequence are stated. Those details are not reported in the registry record. The result is that the design and planned endpoint can be described, while the numerical treatment comparison and its statistical uncertainty cannot be evaluated from the posted information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 4 outcome measures, including the primary outcome and secondary outcomes for average oxygen consumption during each intervention and quality of life assessed by SF-36. It reports 0 analyses. The record does not describe whether additional outcomes or comparisons were planned, how outcomes were prioritized in the analysis, or whether any adjustment for multiple testing was intended. A multiplicity strategy is therefore not reported in the registry record.
In general, testing multiple outcomes or multiple comparisons can increase the chance of obtaining at least one apparently notable result by chance. Methods that account for multiplicity may control that risk, but no such method can be attributed to this trial from the posted record. Because no analyses are reported, there are no outcome-specific estimates to compare or interpret in light of multiplicity.
The registry states that one participant completed autonomic testing for the primary outcome. It does not report the completion status or outcome availability for the other enrolled participants, nor does it give reasons for missing measurements. It also does not report whether missing data were imputed, excluded, or handled by another method. The status of missing data for the secondary outcomes is not reported in the registry record.
In a crossover design, incomplete participation can affect which condition pairs are available for comparison. General analysis choices may include using only complete pairs or using a model that can incorporate available observations under stated assumptions. The registry does not report which approach was used, and no analysis population is specified. The posted information therefore does not establish whether the primary or secondary analyses were based on all enrolled participants, participants who completed both periods, or another group.
These gaps limit interpretation of both the result and its precision. They do not establish why data are missing or why the trial was terminated; those reasons are not reported in the registry record.
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 |
|---|---|---|---|
| CLS-On | 0 | 4 | 0.0% |
| CLS-Off | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| CLS-On | 0 of 4 |
| CLS-Off | 0 of 4 |
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 |
|---|---|
| CLS-On | 0 of 4 |
| CLS-Off | 0 of 4 |
The registry records safety counts separately for the CLS-On and CLS-Off groups. For each group, the serious adverse event count is 0, the other adverse event count is 0, and the death count is 0. The entries list 4 participants at risk in each recorded group for the serious and other adverse event fields. These are group-level registry entries and should be read as posted, not combined into a total.
A count of 0 means that no event was entered in that category for the corresponding group in the registry record. It does not, by itself, show how events were sought, what period was covered, how an event was classified, or whether reporting was complete. Safety collection and ascertainment procedures are not reported in the registry record. Because the study is crossover, the record’s group-level presentation also does not explain how event exposure across treatment periods was represented.
The registry lists no top serious adverse event terms. This indicates that no terms are included in that field; it does not provide further detail about surveillance or attribution. The posted entries should not be interpreted as proof of zero risk or as a comparison demonstrating that one pacing condition is safer than the other. The record does not report a comparative safety analysis or uncertainty around the counts.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-masked crossover trial was registered to examine CLS versus standard rate response in people with congenital heart disease after epicardial pacemaker implantation. It describes a sequence in which each condition was scheduled for 3 months, with autonomic testing intended at 3 months after the start of each intervention. It also identifies a mental-stress heart-rate response as the primary outcome and lists oxygen consumption and quality of life as secondary outcomes.
The posted information does not establish the comparative result. Although the primary outcome is defined as a count of participants with a blunted or unchanged response, no count by condition, treatment contrast, confidence interval, or statistical test is reported. The record states that one participant completed autonomic testing, but does not report the outcome classification or the status of testing for the remaining enrolled participants. No results for the listed secondary outcomes are reported.
Accordingly, the record cannot show the size, direction, or precision of an intervention difference. It does not support a conclusion that CLS improved, worsened, or had no effect on heart-rate response, oxygen consumption, or quality of life. Missing results are not the same as a result showing no difference.
The safety entries report 0 serious adverse events, 0 other adverse events, and 0 deaths in each recorded group. These are descriptive registry counts; the record does not provide the safety methods or a comparative analysis. They should not be generalized beyond the reported entries.
The trial status is terminated, but the reason is not reported in the registry record. The status alone does not explain the termination and does not reveal whether it was related to recruitment, conduct, safety, or another issue. Overall, the registry record documents the study question and design but supplies too little outcome and analysis information for an assessment of treatment effects.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the gap between a registered study design and an interpretable result. The registry specifies a randomized crossover comparison and names a primary outcome, but the posted record contains no analyses. Without outcome counts or an estimated contrast, readers cannot evaluate the direction, size, or precision of the comparison.
The crossover design makes the analysis structure especially important. Measurements under both interventions are linked within participants, and sequence and period may matter to interpretation. These are general features of crossover trials. The registry record does not report how the paired data, periods, or treatment order were handled. A design label alone is not enough to establish that the analysis matched the design.
The primary endpoint also illustrates why definitions matter. “Blunted or unchanged” describes a categorical response, but the registry does not report the rule used to classify participants. Without a definition and the observed classifications, the endpoint cannot be independently interpreted or compared with other studies.
Finally, the record states that one participant completed autonomic testing, while enrollment was 4. It does not explain the testing status of other participants or the analysis population. This makes reporting on participant flow and missing data particularly relevant. The statistical lesson is not that a particular result occurred, but that design, outcome definition, analysis, and completeness of reporting all shape what readers can learn from a trial record.
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 main trial-specific limitation of the posted record is the absence of primary and secondary outcome analyses. Although the registry names a primary endpoint and two secondary outcomes, it reports 0 analyses. No outcome counts by intervention, effect estimates, confidence intervals, or statistical tests are reported. The treatment comparison therefore cannot be quantified.
The primary outcome is described as the number of participants with a blunted or unchanged mental-stress effect on heart rate, but the classification criteria are not reported in the registry record. The record states that one participant completed autonomic testing, without reporting the outcome for that participant or the testing status of other enrolled participants. Participant flow, withdrawals, missing measurements, and the analysis population are not reported.
The registry describes randomization, double masking, and a crossover structure, but does not report the allocation procedure, sequence allocation, masking procedures, adherence, or analysis method. It does not describe handling of within-participant correlation, period effects, sequence effects, or possible carryover. The presence or absence of a washout period is also not reported in the registry record.
The trial is marked terminated, but the reason is not reported. The record does not give a statistical analysis plan, sample-size justification, or details of any interim analyses. The planning description is not a substitute for these details, nor does it provide an observed treatment effect. Together, these omissions limit assessment of both the conduct and the results without establishing why the study ended or what its unreported analyses would have shown.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Specialized Pacing for Patients With Congenital Heart Disease — NCT03361189.
- Registry record last updated 2023-01-20; status last verified 2022-12.
- Results first posted 2023-01-20.
- 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
NCT03361189 is a randomized, double-masked crossover trial of closed loop stimulation and standard rate response in congenital heart disease after epicardial pacemaker implantation. The registry lists phase 2 and phase 3, enrollment of 4, and status as terminated. Its recorded start date is 2021-05-09, and its primary completion date is 2021-11-03. The sponsor is the University of California, Los Angeles.
The primary outcome concerns the number of participants with a blunted or unchanged heart-rate response to mental stress during each intervention. Secondary outcomes include average oxygen consumption and quality of life assessed by SF-36. The registry states that one participant completed autonomic testing, lists 4 outcome measures, and reports 0 analyses. The reason for termination, outcome results, and statistical analysis details are not reported in the registry record.