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 Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure (NCT00588692), a randomized na study. The primary outcome is Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00588692 |
| Phase | NA |
| Condition | Heart Failure |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
Participants had heart failure. The primary endpoint was analyzed in ejection-fraction subgroups based on measurements reported at baseline. The 25-49% subgroup included 48 participants, with 24 in each group. The 35-49% subgroup included 33 participants: 14 in the SphygmoCor Unblinded group and 19 in the SphygmoCor Blinded group. Two participants with ejection fraction either <25 or >50 were not included in the analysis.
Intervention
In the SphygmoCor Unblinded group, investigators used SphygmoCor values to guide medication adjustments intended to optimize heart-failure treatment.
Comparator
In the SphygmoCor Blinded group, SphygmoCor values were hidden from the investigator. The registry record identifies the comparison groups but does not report further details about medication management in the blinded group.
Primary question
The primary endpoint asks how peak oxygen uptake changed from baseline to 6 months, according to ejection-fraction subgroup, and compares the two SphygmoCor strategies. The registry record does not report the group-specific changes or a numerical between-group estimate, so the direction and precision of any difference cannot be assessed from the posted results.
3. Trial Design
The registry record describes a randomized, single-masked, parallel-group study of strategies for aggressive central afterload reduction in people with heart failure. Enrollment was 60. The listed intervention was SphygmoCor, a device. Participants were assigned to a SphygmoCor Unblinded group or a SphygmoCor Blinded group. The record does not explain who was masked or provide additional details about how randomization was generated or implemented.
In the unblinded group, SphygmoCor values were used to determine medication adjustments intended to optimize heart-failure treatment. In the blinded group, those values were hidden from the investigator. Thus, the contrast concerns whether SphygmoCor measurements were available to inform treatment decisions; the record does not describe a comparison between a drug and placebo or give a complete account of other treatment decisions.
The listed study status is completed. The recorded start was 2007-07, and primary completion was 2012-11. The sponsor is Mayo Clinic. Phase is listed as NA. The registry record does not report the protocol’s sample-size justification, details of allocation concealment, or a fuller description of the masking procedures.
The primary endpoint concerns percentage change in peak oxygen uptake during maximal-effort exercise testing, assessed at baseline and 6 months. Results are organized by baseline ejection-fraction subgroup. The record also lists changes in heart rate and multiple cardiac structure and function measures as secondary outcomes. Their presence in the outcome list does not establish that results for each measure were posted or that any particular analysis was prespecified.
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 | SphygmoCor Unblinded | SphygmoCor Blinded |
|---|---|---|
| STARTED | 30 | 30 |
| COMPLETED | 23 | 27 |
| NOT COMPLETED | 7 | 3 |
Reasons for not completing this period:
| Reason | SphygmoCor Unblinded | SphygmoCor Blinded |
|---|---|---|
| Withdrawal by Subject | 4 | 2 |
| Hip Surgery | 0 | 1 |
| Severe Peptic Ulcer Disease | 1 | 0 |
| Cancer | 1 | 0 |
| Death | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: For the EF subgroup 25-49%, n=48, 24 SphygmoCor Unblinded, 24 SphygmoCor Blinded. For the EF subgroup 35-49%, n=33, 14 SphygmoCor Unblinded,. 19 SphygmoCor Blinded. 2 subjects had EF either \<25 or \>50, and they were not included in the analysis.
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: Only the participants who completed the trial were included in the baseline analysis.
| Characteristic | Unit | SphygmoCor Unblinded | SphygmoCor Blinded | Total |
|---|---|---|---|---|
| Participants analysed | 23 | 27 | 50 | |
| Age, Continuous | years | 74 (SD 8) | 72 (SD 8) | 73 (SD 8) |
| Sex: Female, Male: Female | Participants | 7 | 4 | 11 |
| Sex: Female, Male: Male | Participants | 16 | 23 | 39 |
| Region of Enrollment: United States | participants | 23 | 27 | 50 |
| Body Mass Index | kg/m^2 | 29.2 (SD 4.5) | 29.9 (SD 4.6) | 29.6 (SD 4.6) |
| History of Hypertension: Prior Hypertension | participants | 20 | 26 | 46 |
| History of Hypertension: No Prior Hypertension | participants | 3 | 1 | 4 |
| Diabetes: Prior History of Diabetes | participants | 12 | 12 | 24 |
| Diabetes: No History of Diabetes | participants | 11 | 15 | 26 |
| Obesity: Obese at Baseline | participants | 10 | 14 | 24 |
| Obesity: Not Obese at Baseline | participants | 13 | 13 | 26 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups, measured over baseline, 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of change in Peak VO2 |
| Endpoint classification | Continuous Endpoint |
Peak oxygen uptake, or VO2, is the maximum rate of oxygen consumption measured during incremental exercise. The registry describes measurement using standard breath-by-breath expired gas analysis, most typically during exercise on a motorized treadmill. The primary outcome is the percentage of change in peak VO2 from baseline to 6 months, reported as a mean with standard deviation, and considered according to ejection-fraction subgroups based on baseline participant measurements.
Peak VO2 is used as a measure of aerobic physical fitness and exercise capacity. A change in this measure can describe how exercise-related oxygen consumption differs over the study period. It is a continuous outcome: each participant’s measurement can take a range of values, rather than belonging only to categories such as event or no event. A group mean describes the average outcome, while a standard deviation describes the spread of participant measurements around that mean.
The registry record names the outcome and its measurement approach but does not report group means, standard deviations, a between-group estimate, or an interval around that estimate. It therefore does not allow readers to judge the size or precision of the observed difference in peak VO2. The endpoint is not, by itself, a direct report of hospitalization, survival, or another clinical event.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary question is whether the change in peak oxygen uptake differed between the group whose investigators could use SphygmoCor values and the group whose investigators were blinded to those values, within the listed baseline ejection-fraction subgroups. The registry record identifies the endpoint, time points, subgroup definitions, and analysis populations. It does not report the numerical primary results. There is consequently no posted estimate from which to describe the direction or magnitude of a between-group difference, and no confidence interval or p-value with which to assess its precision or statistical compatibility with no difference.
The 25-49% subgroup includes 48 participants, split evenly between the two groups. The 35-49% subgroup includes 33 participants, with 14 in the unblinded group and 19 in the blinded group. These are subgroup counts, not the enrollment count for the whole study. The record says that two participants whose ejection fraction was either <25 or >50 were not included in the primary analysis. The two listed subgroup ranges overlap, so their results should be understood as separately defined analyses rather than assumed to be mutually exclusive categories.
Without the group-specific means and standard deviations, the observed within-group changes cannot be described. Without a between-group estimate and its uncertainty, it is not possible to distinguish a small, imprecisely estimated difference from a larger, more precisely estimated one. The fact that the registry lists an endpoint does not establish that a particular effect was found. Neither a positive nor a negative conclusion about the comparison can be drawn from an outcome title alone.
The registry record lists 16 outcome measures and 32 analyses, but it does not describe how those analyses relate to one another or report a multiplicity strategy. The number of listed analyses makes it especially important not to treat a result for one outcome or subgroup, if encountered elsewhere, as a complete account of the evidence. No p-values or confidence intervals for the primary endpoint are reported in the registry record.
The posted safety information includes serious and other adverse-event counts for groups labeled Treatment and Control. These data are distinct from the primary exercise endpoint. They provide counts of participants at risk and affected, but the record does not report an inferential comparison or enough detail to attribute every listed event to a particular SphygmoCor arm. Descriptive event counts should not be interpreted as proof of a treatment effect.
9. Statistical Methods Explained
What does the primary outcome measure?
The primary measure is percentage change in peak VO2, a continuous measure of oxygen consumption during maximal-effort exercise testing. The registry describes breath-by-breath expired gas analysis and reports that the outcome was assessed at baseline and 6 months. A continuous outcome retains information across a range of measurements. Its mean gives an average, and its standard deviation gives information about variation among participants.
The registry labels the summary measure as a mean and the dispersion measure as a standard deviation. These labels do not supply the actual estimates. Neither the group means nor their standard deviations are reported in the registry record, so the scale and variability of the observed endpoint cannot be examined from the posted results.
How should a comparison of changes be understood?
A change-from-baseline analysis focuses on how measurements differ between the starting assessment and the later assessment. A between-group comparison of changes asks whether the average change differs between the SphygmoCor Unblinded and SphygmoCor Blinded groups. This is conceptually distinct from asking whether one group changed from its own baseline. A change in one group alone does not establish that the groups changed differently.
General statistical explanation: an estimated difference is a summary of the contrast between groups, while a confidence interval describes uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval. A p-value addresses compatibility between the data and a specified statistical null model; it does not measure the size or clinical importance of an effect. The registry record does not report a primary between-group estimate, confidence interval, or p-value.
Why do the ejection-fraction subgroups matter?
The primary endpoint is presented according to ejection-fraction subgroups based on baseline reports. The registry lists a 25-49% group and a 35-49% group, and reports separate analysis counts for each. Because those ranges overlap, they should not be treated as two non-overlapping strata without further information. The record does not explain the rationale for these specific subgroup definitions or how subgroup comparisons were incorporated into the analysis plan.
The record states that two participants with ejection fraction either <25 or >50 were not included in the analysis. This makes the analyzed primary populations different from a simple reading of total enrollment. It does not, on its own, explain whether other participants had missing measurements, were excluded for other reasons, or contributed to other outcomes.
What can be inferred from randomization and masking?
Random assignment is intended to make comparison groups similar, on average, with respect to measured and unmeasured characteristics. In a small study, chance differences can remain, and randomization does not remove uncertainty in an estimate. The registry identifies the study as randomized, single-masked, and parallel, but does not report the randomization method, allocation concealment, or who was masked. The intervention descriptions clarify that investigators could see SphygmoCor values in one group and were blinded to them in the other; they do not fully describe masking of participants or outcome assessors.
The two groups differ in whether SphygmoCor readings were available to guide medication adjustments. Interpretation therefore depends on understanding the broader care and measurement procedures, which are not fully detailed in the registry record. The listed design alone does not show that all other aspects of care were identical.
What do planning calculations mean?
General statistical explanation: sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. A planning illustration based on an observed effect is not the same as a trial’s original sample-size justification, and it is not observed power. Such an illustration depends on its assumptions, including the effect size used. The registry record does not report the trial’s own sample-size justification. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. No numerical planning estimate is reported in the registry record.
General statistical explanation: continuous outcomes may have variability that differs from the assumptions of a simple normal model. Over-dispersion means that observed variability is greater than a model expects; if not accounted for, standard errors and intervals may be too small. The registry record does not state whether over-dispersion was assessed or what statistical model was used. It is therefore not possible to reconstruct the analysis or assess its model assumptions from the outcome description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 16 outcome measures and 32 analyses. It does not report whether the analyses were arranged into a prespecified hierarchy, whether a single primary comparison was protected from the effects of multiple testing, or whether any adjustment for multiplicity was used. When many outcomes or subgroup analyses are examined, the chance of at least one apparently unusual result can increase. General statistical explanation: multiplicity procedures can control that risk, but their choice depends on which comparisons were planned and how they relate. The record does not provide enough information to describe such a procedure.
For the primary endpoint, the record identifies baseline and 6-month measurement and two ejection-fraction subgroup definitions. It does not report the planned statistical model, covariate adjustment, handling of repeated measurements, or the hierarchy between subgroup analyses. The outcome title and summary statistics format do not establish whether the analysis compared changes directly or used another model.
Missing-data methods and the extent of missing primary measurements are not reported in the registry record. The two participants with ejection fraction either <25 or >50 were not included in the primary analysis, but this is a stated exclusion based on subgroup eligibility, not a complete account of missing data. The record does not explain whether other participants lacked 6-month measurements or how any such observations were handled.
The record also does not describe the analysis population in terms of intention-to-treat, per-protocol, or another approach. Randomization is reported, but that fact alone does not specify which participants were included in each analysis. Without analysis-population and missing-data details, readers cannot assess whether the reported primary results, which are themselves not numerically posted in the registry record, would represent all randomized participants or a subset.
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 |
|---|---|---|---|
| Treatment | 3 | 24 | 12.5% |
| Control | 2 | 27 | 7.4% |
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 |
|---|---|
| Treatment | 10 of 24 |
| Control | 5 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment | Control |
|---|---|---|---|
| Heart Failure Hospitalization | Cardiac disorders | 2 of 24 | 2 of 27 |
| Death | Cardiac disorders | 1 of 24 | 0 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment | Control |
|---|---|---|---|
| Dizziness | Nervous system disorders | 8 of 24 | 5 of 27 |
| Worsening Renal Function | Renal and urinary disorders | 2 of 24 | 0 of 27 |
Serious events with the highest arm-level rate: heart failure hospitalization (8.3%), death (4.2%).
The adverse-event summary uses group labels Treatment and Control. For serious adverse events, it reports 24 participants at risk and 3 affected in Treatment, and 27 at risk and 2 affected in Control. For other adverse events, it reports 24 at risk and 10 affected in Treatment, and 27 at risk and 5 affected in Control. These are counts of affected participants, not a statistical comparison. The registry record does not report a confidence interval, p-value, or adjusted analysis for these differences.
The record lists Heart Failure Hospitalization at 8.3% and Death at 4.2% among the top serious terms. Those term percentages do not provide group-specific counts in the adverse-event summary. The group-level death fields are not populated with counts. The record does not provide enough information to match each term to a particular group or to establish the timing, duration, or causal attribution of events.
Safety counts are descriptive. Differences in counts can reflect chance, the number of participants at risk, follow-up, event definitions, and how events were collected. The registry record does not give all these details. The figures should not be read as evidence that one strategy caused more or fewer events, and they do not establish whether a particular event was related to the intervention.
12. What the Result Does, and Does Not, Mean
The registry record defines a clinically oriented comparison: investigators either used SphygmoCor measurements to guide medication adjustments or were blinded to those measurements. It identifies change in peak oxygen uptake as the primary endpoint, with evaluation from baseline to 6 months and analyses by baseline ejection-fraction subgroup. These details establish what the study intended to examine, but they do not reveal the observed primary result.
The primary endpoint’s numerical results are not reported in the registry record. No group-specific mean changes, standard deviations, between-group estimates, confidence intervals, or p-values are available in the posted results. Accordingly, the direction, magnitude, statistical precision, and compatibility with no difference cannot be evaluated from this record. The absence of a numerical result is not evidence that there was no effect; it means the record does not report the information needed to assess one.
Even if a difference in peak VO2 were available, the endpoint would describe exercise-related oxygen consumption rather than directly establish a difference in hospitalization, survival, or every aspect of heart failure. The registry lists secondary measures, including heart rate and left-ventricular and mitral-flow measures, but listing an outcome does not establish what its result was. The posted safety counts also do not by themselves establish cause or comparative risk.
General statistical explanation: interpretation depends on both the estimated effect and its uncertainty, along with the outcome’s relevance and the study’s design. A confidence interval can show which effect sizes are reasonably compatible with the data under an analysis model; a p-value alone cannot communicate the size or practical importance of a difference. Here, the record does not provide these primary statistical results, so a conclusion about the comparative effect would go beyond the available registry information.
The study’s completed status indicates that the registry marks it completed, not that every outcome result is available in the record. Readers should separate the presence of a registered question from the presence of a reported answer.
13. Why This Trial Matters Statistically
This trial is statistically interesting because the randomized contrast concerns an information-guided strategy: whether investigators could use SphygmoCor values when adjusting medication. The comparison is not simply between possession and non-possession of a device. As described in the registry, the availability of measurement values is tied to treatment decisions in the unblinded group, while values are hidden from investigators in the blinded group. Interpreting such a strategy comparison requires clarity about which decisions could differ and how outcomes were measured.
The primary endpoint is continuous and assessed at baseline and 6 months. These features bring familiar statistical questions: whether the analysis compares changes between groups, how repeated measurements are handled, and how uncertainty is represented. The registry gives the measurement definition and summary format but does not report the analysis model or numerical primary results. That gap illustrates why an endpoint description is not a substitute for a complete statistical report.
Subgroup reporting adds another layer. The stated ejection-fraction ranges overlap, and the registry gives different group counts for each. This makes it important to understand whether the subgroup analyses were planned and how their results relate to the overall comparison. The record does not report that rationale or a multiplicity approach. With multiple listed outcomes and analyses, readers need those details to distinguish a prespecified primary inference from exploratory findings.
The registry also reports adverse-event counts, but those counts have a different purpose from an efficacy endpoint and do not constitute a formal comparative safety analysis. Taken together, the record shows the importance of reporting estimates, uncertainty, analysis populations, and missing-data handling alongside trial design and outcome definitions. Without those elements, readers can identify the question and design but cannot judge the strength or precision of the primary statistical evidence.
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.
A central limitation of the registry record is that it does not report numerical results for the primary endpoint. The group-specific changes, standard deviations, between-group estimate, confidence interval, and p-value are not reported in the registry record. Consequently, the principal comparison cannot be quantified or assessed for precision using the posted information.
The primary analysis is described for two baseline ejection-fraction ranges, 25-49% and 35-49%, which overlap. The registry does not explain why these ranges were selected, whether other subgroup definitions were planned, or how these analyses relate to a broader overall analysis. It reports that two participants with ejection fraction either <25 or >50 were not included, but does not give a full account of all exclusions or missing measurements.
Important elements of statistical methods are not reported in the registry record. These include the primary analysis model, the handling of repeated measurements, covariate adjustment, missing-data methods, analysis population, and multiplicity strategy. The record identifies randomization and single masking but does not give the randomization procedure, allocation concealment, or a complete description of who was masked.
The intervention description explains that SphygmoCor values informed medication adjustments in one group and were hidden in the other, but the registry does not provide a complete account of other care decisions or how adherence to the assigned strategy was assessed. The adverse-event summary offers counts and selected serious-event terms without a full inferential comparison or group-specific allocation for the listed terms. These reporting limits constrain interpretation; they do not establish that unreported methods or results were not collected elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure — NCT00588692.
- Registry record last updated 2014-05-06; status last verified 2014-04.
- Results first posted 2014-05-06.
- 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 completed registry record describes a randomized, single-masked, parallel-group study with enrollment of 60 and sponsorship by Mayo Clinic. The intervention was SphygmoCor-guided medication adjustment, compared with a group in which SphygmoCor values were blinded to investigators. The primary outcome was percentage change in peak oxygen uptake from baseline to 6 months, analyzed by baseline ejection-fraction subgroup.
The registry lists secondary cardiac and exercise-related outcomes, 16 outcome measures, and 32 analyses. It also reports adverse-event counts for groups labeled Treatment and Control. Numerical primary endpoint results, the detailed statistical analysis plan, missing-data methods, and multiplicity procedures are not reported in the registry record. The posted information therefore describes the study question and design, but does not allow the primary comparative effect or its precision to be evaluated.