Sensor Optimization of Cardiac Resynchronization Therapy Response: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sensor Optimization of Cardiac Resynchronization Therapy Response (NCT01832493), a na na study. The primary outcome is AV Interval Determination Using Impedance.

2. Clinical Question

The SOCR Study concerns patients with heart failure who are indicated for cardiac resynchronization therapy (CRT). During device implantation, the study examined whether intracardiac impedance could identify an atrioventricular (AV) pacing interval close to the interval selected using LV dP/dt max. The registry describes an acute feasibility question: whether measurements from implanted sensors can help identify settings during the procedure, not whether a sensor-guided strategy changes longer-term health outcomes.

The registry does not report the primary endpoint result, so the proportion of eligible patients meeting this agreement criterion cannot be described from the record. Nor does the stated question establish that either method improves clinical outcomes; it addresses agreement between methods for an acute programming decision.

3. Trial Design

The registry describes the Sensor Optimization of CRT Response (SOCR) Study as a multicenter, prospective, non-randomized, acute feasibility study. Its stated purpose was to determine whether subcutaneous heart sounds and/or intracardiac impedance could acutely identify optimal AV pacing intervals and optimal left ventricular electrodes in patients indicated for CRT. The primary endpoint concerns AV interval determination using impedance.

The study is listed as a single-group study, with an enrollment of 50 and a completed status. The intervention is a cardiac resynchronization therapy device, and the arm description states that patients were implanted with such a device. The record lists allocation as not applicable and masking as none. It lists phase as not applicable. The sponsor is Medtronic Cardiac Rhythm and Heart Failure. The recorded study start is 2013-07 and primary completion is 2016-01.

Because this is not a randomized comparison, the study does not have a like-for-like control arm for estimating a treatment contrast. The comparison described for the primary endpoint is between sensor-derived AV interval selection and LV dP/dt max-derived selection within the procedural measurement context. The overall enrollment is not necessarily the endpoint denominator: the endpoint population specifically requires both types of measurement for all AV intervals of interest. The number meeting that measurement requirement is not reported in the registry record.

The registry record does not report a sample-size justification, detailed protocol, or further study procedures. The acute feasibility framing is important when interpreting scope: the stated study question concerns identifying settings during implantation, rather than establishing a longer-term effect on clinical 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: Eight patients exited the study prior to undergoing the research procedure: Four did not meet inclusion/exclusion criteria; In 2 cases, the physician deemed withdrawal medically necessary; and in 2 cases, the surgeon was unable to place the left ventricular (LV) lead.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients with a RV tripolar intracardiac impedance measurement and a LV dP/dT max measurement for all AV intervals of interest.

5. Baseline Characteristics

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

Population: Patients undergoing the research procedure

6. Primary Endpoint

The registry lists the primary outcome as AV Interval Determination Using Impedance, measured over During implant.

The primary endpoint is the number of patients for whom the optimal AV interval identified by intracardiac impedance agrees within one AV interval setting of the interval identified by LV dP/dt max. The registry defines one setting as 30 milliseconds and specifies that measurements are made during implant. The endpoint population includes patients with a right-ventricular tripolar intracardiac impedance measurement and an LV dP/dt max measurement for all AV intervals of interest.

The endpoint is used to assess whether the sensor-based measurement gives a setting close to the reference method described in the registry. Agreement within the stated tolerance makes the endpoint a measure of concordance at a clinically specified programming resolution, rather than a comparison of patient outcomes. The registry describes LV dP/dt max as current practice for determining AV interval programming and intracardiac impedance as a possible alternative method.

The result would need to be interpreted with its denominator: the endpoint is defined for patients with the required measurements, not automatically for every enrolled patient. Neither the number meeting the agreement definition nor the number with complete qualifying measurements is reported in the registry record. Therefore, the endpoint’s observed frequency and its precision cannot be assessed from the registry information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: The primary endpoint is binary at the participant level. Each participant either meets the stated agreement criterion or does not, provided the required measurements are available. A count of participants meeting the criterion can describe the observed frequency, but that count needs a clearly stated denominator to be interpretable. The registry defines the qualifying measurement population, but does not report its size or the observed count.

What does agreement mean?

Agreement asks whether two methods assign sufficiently similar settings under a defined tolerance. In this study, the tolerance is one AV interval setting, defined as 30 milliseconds. This is different from asking whether the methods produce identical values in every case, and different from asking whether one method improves an outcome. The endpoint is also not a conventional randomized treatment contrast: the methods are assessed against each other in a procedural setting, with LV dP/dt max described as the reference.

General statistical explanation: A confidence interval gives a range of values compatible with the observed data under the chosen statistical model. For a binary endpoint, an interval around the observed proportion can communicate uncertainty that a count alone cannot. Its width depends on factors including the number of participants in the endpoint denominator and the observed proportion. No confidence interval or observed proportion is reported in the registry record, so the precision of the endpoint estimate cannot be evaluated.

Why does the denominator matter?

The endpoint population requires both an intracardiac impedance measurement and an LV dP/dt max measurement for all AV intervals of interest. The enrolled group and the endpoint-eligible group may therefore differ. A complete account would identify how many enrolled participants had the necessary measurements and how many were included in the endpoint analysis. Those counts and the handling of incomplete measurements are not reported in the registry record. It is not possible to infer whether missing measurements occurred or how they affected the analysis.

General statistical explanation: When a measurement is missing, an analysis may be affected if the participants with missing data differ systematically from those with complete data. Statistical approaches for missing observations depend on the reasons for missingness and the endpoint. Without a reported missing-data plan and participant counts, readers cannot assess whether the reported endpoint, if available, would represent all enrolled participants or only those with complete measurements.

How should planning assumptions be read?

The registry’s planning assumptions describe an illustration based on two arms with equal allocation, a two-sided significance level of 0.05, and a normal approximation. The illustration is described as using a stated fraction of an observed effect. Such assumptions describe a planning calculation, not a result from the trial and not observed power. They do not establish the study’s original enrollment rationale; a study-specific sample-size justification is not reported in the registry record.

The two-arm illustration should also be distinguished from the recorded design. SOCR is listed as a single-group, non-randomized study, and the primary endpoint compares measurement methods rather than randomized arms. A planning illustration built around two arms is not a description of the actual allocation. The registry does not report a protocol-level statistical analysis plan explaining how the primary endpoint was analyzed.

What does over-dispersion mean in general?

General statistical explanation: Over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make uncertainty estimates too small if the model does not account for the extra variability. This issue is most relevant to certain count-data models. The primary endpoint is described as a participant count meeting a binary criterion, and the registry does not report a model or variance analysis that would allow over-dispersion to be assessed. No conclusion about it can be drawn for this study.

Finally, a feasibility study can be informative about whether a measurement approach can be assessed during a procedure, but a feasibility label does not itself guarantee that measurements were complete, that a threshold was met, or that a later trial would find a similar result. For this record, the primary endpoint result and analysis details are not reported, limiting statistical interpretation to the question and design as registered.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cardiac Resynchronization Therapy")
n      <- c(28)
events <- c(14)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cardiac Resynchronization Therapy  28  14  50.0  30.6  69.4  32.6  67.4  32.5  67.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, but it does not report a testing hierarchy, multiplicity adjustment, or plan for interpreting several statistical tests together. It also lists no analysis records. The primary endpoint is identified, but its relationship to the other outcome measures in a prespecified testing sequence is not reported in the registry record.

General statistical explanation: When a study makes multiple statistical comparisons, the chance of at least one apparently notable result can increase if each comparison is judged separately. A prespecified hierarchy or adjustment can help address that issue. Without a reported plan, it is not possible to determine how the study handled multiplicity or whether formal hypothesis tests were intended for the outcomes.

The endpoint population requires measurements from both intracardiac impedance and LV dP/dt max for all AV intervals of interest. The registry does not report the number of participants meeting that requirement, the number with incomplete measurements, or a missing-data procedure. It also does not state whether any participants were excluded from an analysis or how such exclusions were defined. Enrollment of 50 should not be assumed to be the denominator for the primary endpoint.

The analysis population is not reported in the registry record. There is no description of whether the endpoint analysis included all enrolled patients, only patients with the specified measurements, or another group. The record does not report sensitivity analyses for incomplete measurements or alternative endpoint definitions. These omissions prevent assessment of how missing observations or analysis-set choices may have influenced the result.

12. 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: device stimulation issue (2.0%), anaphylactic shock (2.0%), myocardial infarction (2.0%).

For the group titled All Enrolled Patients, the registry lists 50 patients at risk, 3 serious adverse events, and 0 other adverse events. It separately lists Device Stimulation Issue, Anaphylactic Shock, and Myocardial Infarction at 2.0% each among the serious adverse event terms. These are the safety figures recorded; the registry does not provide further context for interpreting their timing or relationship to the device or procedure.

The adverse-event entries should not be read as evidence that the study established a causal relationship. The registry record does not report an attribution assessment, a comparison group, or additional event-level details. It also does not clarify in the information available whether each reported event term corresponds to a distinct participant. The field for deaths is not reported in the registry record, so the record does not support a statement about deaths.

Zero other adverse events in the registry field means none were recorded in that category there; it does not establish that no unrecorded or unreported events occurred. The safety figures are descriptive, and the registry does not report a comparative safety analysis.

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

The registered question is specific: can intracardiac impedance identify an AV interval within one setting, or 30 milliseconds, of the setting identified by LV dP/dt max during implantation? The registry describes a prospective, non-randomized, acute feasibility study directed at this measurement question. It does not report the primary endpoint result, so the observed level of agreement cannot be stated.

Even if an agreement estimate were available, agreement between two methods would not by itself show that either method improves patient outcomes. It would address how closely their selected settings correspond under the study’s endpoint definition. The registry’s description does not establish a causal comparison between sensor-guided programming and another treatment strategy, because the study is single-group and non-randomized.

The endpoint is restricted to patients with the specified measurements across the AV intervals of interest. Since the number meeting those requirements is not reported, the enrolled group of 50 cannot automatically be treated as the endpoint denominator. The registry also does not provide an estimate with an uncertainty interval, so the precision and stability of any observed agreement result cannot be assessed from the record.

The record lists serious adverse-event information, but those descriptive entries do not establish causation or comparative risk. The study’s feasibility framing and acute measurement focus also limit what can be inferred about outcomes beyond the implantation setting. No longer-term clinical outcome result or randomized treatment comparison is reported in the registry record.

Accordingly, the defensible interpretation is about scope: the study was designed to examine acute agreement between a sensor-based method and the stated reference method. Whether the criterion was met, how often it was met, and how reliably it could be estimated are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for distinguishing a method-agreement question from a treatment-effect question. The primary endpoint counts patients whose impedance-derived AV interval is within a prespecified tolerance of the setting derived from LV dP/dt max. That is a direct way to frame an acute measurement objective, but it does not answer whether using one method rather than another changes later clinical outcomes.

The record also highlights why population definitions matter. The primary endpoint applies to patients with the required measurements across the AV intervals of interest, while the overall enrollment is 50. Without the qualifying denominator and the endpoint count, readers cannot estimate agreement or judge its precision. A clearly stated endpoint is necessary, but it is not sufficient for interpreting results in the absence of the observations and analysis details.

Design context matters as well. The study is single-group and non-randomized, with no like-for-like control arm. The comparison of measurement methods should therefore not be mistaken for a randomized comparison of treatment strategies. The registry’s two-arm planning assumptions are illustrations and do not alter the recorded study design or provide evidence of observed power.

Finally, the record identifies four outcome measures but does not report a multiplicity plan, missing-data approach, or analysis population. Those details are important for understanding how a result was selected, who contributed to it, and how uncertainty was handled. Their absence, along with the missing primary endpoint result, makes this record useful for defining the statistical question but insufficient for judging the empirical answer.

15. 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 is that the primary endpoint result is not reported in the registry record. The number of patients meeting the agreement criterion, the eligible endpoint denominator, and an uncertainty estimate are also not reported. As a result, the main statistical question cannot be answered from the registry information.

The record specifies that eligible patients must have both right-ventricular tripolar intracardiac impedance and LV dP/dt max measurements for all AV intervals of interest, but does not describe measurement completeness, exclusions, or missing-data handling. It is therefore unclear how the endpoint population relates to the enrollment of 50.

The study is described as multicenter, prospective, non-randomized, single-group, and acute. The registry does not report how many centers contributed data, whether measurement procedures were standardized across centers, or whether center-level variation was considered in the analysis. It also does not report a detailed analysis plan, the statistical method for the primary endpoint, or a multiplicity strategy for the four outcome measures.

The record does not report a study-specific sample-size justification, an analysis population, or longer-term clinical results for the primary question. The serious adverse-event entries are descriptive, and their timing, attribution, and event-level details are not reported. These limitations constrain interpretation to the registered design and endpoint definition rather than an assessment of the observed result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sensor Optimization of Cardiac Resynchronization Therapy Response — NCT01832493.
• Registry record last updated 2016-08-29; status last verified 2016-07.
• Results first posted 2016-08-29.
• 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.

19. Record Summary

NCT01832493 is the completed SOCR Study, a multicenter, prospective, non-randomized acute feasibility study of cardiac resynchronization therapy sensor optimization. The registry lists an enrollment of 50, a start date of 2013-07, and primary completion in 2016-01. The study is single-group, with no masking, and evaluates whether sensor measurements can identify optimal settings during implantation.

The primary endpoint is the number of patients whose impedance-derived AV interval agrees within one setting, defined as 30 milliseconds, of the interval identified by LV dP/dt max. The endpoint result, eligible denominator, analysis population, and statistical uncertainty are not reported in the registry record. The record lists four outcome measures and no analysis records. Safety entries include 3 serious adverse events and 0 other adverse events among 50 patients at risk; deaths are not reported in the registry record.