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 Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy (NCT01567826), a randomized phase 4 study. The primary outcome is Lipiscan - Lipid Core Burden Index (LCBI).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01567826 |
| Phase | Phase 4 |
| Condition | Coronary Artery Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 87 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Annapoorna Kini |
| Results posted | Yes |
2. Clinical Question
Population
People with coronary artery disease undergoing assessment of a nonculprit obstructive lesion. The primary-outcome record notes that data were unavailable for 17 patients, listing loss to follow-up, image-formatting problems, and NIRS console or catheter malfunction among the reasons. It also mentions disc integrity or corruption. The record does not give a more detailed eligibility description in the information available.
Intervention
Aggressive lipid-lowering therapy, described in the arm information as Crestor. The brief study summary describes intensive therapy as rosuvastatin 40 mg and says rosuvastatin doses of 10–40 mg would be used. The registry record does not explain how these descriptions relate to one another or give an individual treatment schedule.
Comparator
Standard-of-care lipid-lowering therapy, described as Zocor or Lipitor. The brief summary refers to standard-care therapy with atorvastatin or simvastatin. The record does not give further details about selection or dosing of comparator treatment.
Primary question
How does the maximum lipid-core burden index in a nonculprit obstructive lesion change from baseline to 6–8 weeks after intervention, and how does that change compare between the aggressive and standard-care therapy groups? LCBI is derived from near-infrared spectroscopy images by relating yellow pixels to viable pixels. Although the registry identifies this as the primary endpoint, it does not report a single comparison of the endpoint results.
3. Trial Design
The registry identifies this as a randomized, single-masked, parallel-group phase 4 study of lipid-lowering therapy in coronary artery disease. It is recorded as completed. The study is described as single-site in the brief summary. The recorded enrollment is 87. Separately, that summary describes a plan to randomize 100 subjects, including 40 assigned to intensive therapy and 40 to standard care. These enrollment descriptions do not match, and the record does not explain the difference. The planned figures should not be treated as the observed allocation or analysis population.
The comparison was between aggressive lipid therapy and standard-of-care lipid therapy. Arm descriptions identify Crestor for the aggressive-therapy group and Zocor or Lipitor for the standard-care group. The summary also refers to rosuvastatin 10–40 mg and atorvastatin or simvastatin. The registry does not clarify individual doses, treatment changes, adherence, or the specific rules for choosing a drug.
The primary endpoint was Lipiscan lipid-core burden index (LCBI), assessed at baseline and 6–8 weeks after intervention. LCBI was derived from near-infrared spectroscopy information. The record says the maximum LCBI for each nonculprit obstructive lesion was recorded for comparison. It identifies the reported summary measure as the median and the dispersion measure as the interquartile range.
The listed study dates are 2010-05 for the start and 2012-02 for primary completion. The registry lists 10 outcome measures and 2 analyses, but does not provide enough information in the primary-outcome entry to identify one numerical treatment-effect comparison. The analysis population, allocation concealment procedures, and the party masked 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 | Standard of Care Lipid Therapy | Aggressive Lipid Therapy |
|---|---|---|
| STARTED | 43 | 44 |
| COMPLETED | 40 | 42 |
| NOT COMPLETED | 3 | 2 |
Reasons for not completing this period:
| Reason | Standard of Care Lipid Therapy | Aggressive Lipid Therapy |
|---|---|---|
| Lost to Follow-up | 3 | 2 |
Analysis population for the primary outcome, as defined in the registry: Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4).
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 | Standard of Care Lipid Therapy | Aggressive Lipid Therapy | Total |
|---|---|---|---|---|
| Participants analysed | 43 | 44 | 87 | |
| Age, Continuous | years | 62.9 (SD 9.8) | 64.4 (SD 9.29) | 63.6 (SD 9.5) |
| Sex: Female, Male: Female | Participants | 12 | 9 | 21 |
| Sex: Female, Male: Male | Participants | 31 | 35 | 66 |
| Current tobacco use: yes | participants | 4 | 9 | 13 |
| Current tobacco use: no | participants | 39 | 35 | 74 |
| Hypertension: yes | participants | 40 | 40 | 80 |
| Hypertension: no | participants | 3 | 4 | 7 |
| Hypercholesterolemia: yes | participants | 40 | 39 | 79 |
| Hypercholesterolemia: no | participants | 3 | 5 | 8 |
| Diabetes mellitus: yes | participants | 3 | 5 | 8 |
| Diabetes mellitus: no | participants | 40 | 39 | 79 |
| Prior CVA/TIA: yes | participants | 3 | 2 | 5 |
| Prior CVA/TIA: no | participants | 40 | 42 | 82 |
| Previous MI: yes | participants | 8 | 8 | 16 |
| Previous MI: no | participants | 35 | 36 | 71 |
| Previous PCI: yes | participants | 20 | 16 | 36 |
| Previous PCI: no | participants | 23 | 28 | 51 |
| Statin Use: yes | participants | 35 | 37 | 72 |
| Statin Use: no | participants | 8 | 7 | 15 |
| Beta-blocker use: yes | participants | 30 | 33 | 63 |
| Beta-blocker use: no | participants | 13 | 11 | 24 |
| ACE-I/ARB use: yes | participants | 19 | 16 | 35 |
| ACE-I/ARB use: no | participants | 24 | 28 | 52 |
| Creatinine | mg/dl | 1.1 (SD 1.3) | 1.0 (SD 0.3) | 1.04 (SD 0.96) |
| LAD Coronary vessel: yes | participants | 17 | 20 | 37 |
| LAD Coronary vessel: no | participants | 26 | 24 | 50 |
6. Primary Endpoint
The registry lists the primary outcome as Lipiscan - Lipid Core Burden Index (LCBI), measured over at baseline and at 6-8 weeks after intervention.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ratio |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is Lipiscan lipid-core burden index (LCBI), a measure derived from near-infrared spectroscopy (NIRS). The registry describes a process in which information from raw spectra is converted into a probability of lipid core and mapped to a red-to-yellow color scale: lower probability is represented as red and higher probability as yellow. Yellow pixels in the analyzed segment are divided by all viable pixels to generate LCBI. The maximum LCBI for each nonculprit obstructive lesion is recorded.
In general, an image-based measure can help quantify a feature that is not readily captured by a broad clinical event count. Here, the registry frames LCBI as an indicator of yellow plaque content in the atherosclerotic lipid pool. A baseline and follow-up assessment gives a way to describe how this measure changes over the stated interval, while the randomized treatment groups provide the intended comparison. The measure is reported as a median with an interquartile range, which describes the middle of the observed distribution and its central spread without requiring a symmetric distribution.
The record does not report the group-specific median values, interquartile ranges, change scores, or a numerical between-group estimate. It therefore does not establish the direction or precision of any difference in LCBI.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry identifies LCBI as the primary endpoint but does not present a single primary-outcome comparison. It describes assessment at baseline and 6–8 weeks after intervention, and it states that the median and interquartile range were the intended summary measures. However, group results and an estimate of the treatment contrast are not reported in the registry record. There is consequently no endpoint estimate or confidence interval in the record from which to describe the magnitude, direction, or precision of a group difference.
The registry’s note that the primary outcome has several categories or time points and was not reduced to one comparison reinforces this limitation. It would be inappropriate to select one time point, category, or analysis as the decisive result without a specified rationale. Nor can a conclusion about change within either group substitute for the randomized between-group contrast. A within-group change may reflect multiple influences over time; the treatment comparison is the relevant quantity for assessing the difference associated with assignment under the study design.
The planned observation window is short, extending from baseline to 6–8 weeks after intervention. The record therefore describes an imaging endpoint over that interval, not a long-term clinical outcome. Secondary outcomes include intravascular ultrasound parameters, fractional flow reserve, diameter stenosis, post-PCI cardiac enzymes, major adverse cardiac events, and high-sensitivity C-reactive protein. Their presence broadens the set of recorded outcomes, but their names alone do not give results or establish a treatment effect.
Safety information is reported separately. The registry lists serious adverse events in both groups and other adverse events in both groups, as well as hospitalization as a leading serious-event term. Those counts should be read as recorded safety observations, not as a substitute for the missing primary endpoint comparison. The record does not provide enough detail to determine whether event ascertainment periods, definitions, or exposure time were identical across groups.
Planning illustrations are not observed evidence of treatment effect. The registry describes illustrations based on a fraction of the observed effect and specified statistical assumptions, but the available primary endpoint record does not present the underlying result or numerical illustration values. They cannot fill the gap in the reported primary comparison, and they are not observed power. Overall, the registry supports a description of the question, measurement, and design, but not a quantitative conclusion about the primary endpoint.
9. Statistical Methods Explained
The registry names the primary measure and its descriptive statistics, but does not report the primary comparison itself or a detailed statistical analysis plan. The methods below explain the statistical ideas relevant to interpreting the stated design; general explanations are not claims about analyses actually used in this trial.
What does the median and interquartile range describe?
The median is the central value after observations are ordered. The interquartile range describes the spread of the middle half of those observations. In general, these summaries can be useful when a measure is skewed or contains influential extreme values, because they do not rely on the mean and standard deviation to characterize the distribution. The registry specifies the median and interquartile range for LCBI, but does not report the resulting summaries.
A difference between group medians is not automatically the same as the median of individual changes. For a baseline-to-follow-up endpoint, analysts might summarize change for each participant and compare those changes, or they might use a model that accounts for baseline values and follow-up measurements. These approaches answer related but not identical questions. The registry record does not state which method was used, whether the reported medians refer to baseline, follow-up, or change, or how the treatment contrast was estimated.
Why does the comparison need a clear definition?
Random allocation is intended to make treatment groups comparable on average at the start of a study. The statistical comparison should then estimate a contrast between the assigned groups, with a clear definition of the endpoint, time point, and analysis population. A result for one group alone does not answer whether outcomes differ between groups. Similarly, a change from baseline within one arm does not by itself isolate the effect of treatment assignment.
Here, the outcome is described across baseline and 6–8 weeks after intervention, while the registry also flags multiple categories or time points and says the primary outcome was not reduced to one comparison. A reader therefore cannot identify from this record which comparison should be treated as the single primary estimate. The specific model, hypothesis test, confidence interval method, and any baseline adjustment are not reported in the registry record.
How should uncertainty be read?
In general, a confidence interval gives a range of estimates compatible with the data under the model and assumptions used. It communicates precision as well as the direction and size of an estimated contrast. A narrow interval indicates greater statistical precision than a wide interval, though neither guarantees that the model or measurement is free of bias. No confidence interval for the primary treatment comparison is reported in the registry record, so its precision cannot be assessed.
A p-value, when reported, describes how incompatible the data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of an effect. The registry record does not report a primary-outcome p-value or identify a primary statistical test. No significance claim can be reconstructed from the endpoint description alone.
What do the planning illustrations mean?
The registry describes sample-size planning illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are based on a stated fraction of the observed effect. In general, such calculations ask how many participants per arm would be needed to detect an assumed effect under specified design and modeling assumptions. The assumed effect and the resulting numerical planning values are not included in the primary endpoint information, so those calculations cannot be independently interpreted from this record.
These are planning illustrations, not a measure of the trial’s observed power. Observed power is not a substitute for an effect estimate and its confidence interval. A post hoc calculation based on an observed estimate can be especially difficult to interpret because it re-expresses the estimated effect and its uncertainty rather than adding independent evidence. The registry does not report the sample-size justification used for the trial’s actual design, so the planning illustrations should not be presented as the original design rationale.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors may be too small and uncertainty may be understated. Methods that accommodate extra variability can improve inference when their assumptions fit the data. The registry’s primary endpoint is summarized by a median and interquartile range, and it does not identify a model in which over-dispersion was assessed or report whether it was relevant. This general issue should not be mistaken for a documented feature of this analysis.
Interpretation also depends on how the image-derived endpoint was processed and how unavailable measurements were handled. The registry describes offline analysis using Matlab-based software and reports reasons for unavailable data, but it does not describe quality-control rules, imputation, sensitivity analyses, or handling of lesions when image data could not be analyzed. Those omissions limit an independent assessment of the reported methods.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures and 2 analyses, alongside several secondary outcomes. The primary endpoint description refers to baseline and 6–8 weeks after intervention, and the record notes that the primary outcome has several categories or time points and was not reduced to one comparison. When multiple outcomes, time points, or analysis choices are considered, the chance of at least one apparently unusual result can increase. In general, a prespecified primary comparison and a multiplicity strategy help clarify which findings are confirmatory and how uncertainty should be interpreted. The multiplicity adjustment, if any, is not reported in the registry record.
The endpoint population note says data were unavailable for 17 patients. Listed reasons include loss to follow-up, incorrect image formatting that could not be recovered at core-laboratory analysis, NIRS console or catheter malfunction at index PCI, and loss of disc integrity or corruption. The record does not give the full detail of the last listed reason in the available text, nor does it report how missing endpoint values were handled. It does not state whether analyses used complete cases, imputation, or another approach, or whether sensitivity analyses assessed the effect of missing data.
The record also does not identify the primary analysis population, such as whether participants were analyzed according to randomized assignment, or describe exclusions after randomization. These details matter because exclusions and unavailable measurements can affect how representative the analyzed observations are of the randomized groups. The registry enrollment entry is 87, while the brief summary describes a plan for 100 subjects and 40 in each treatment group. The record does not reconcile these figures; neither should be assumed to represent the number with an evaluable primary endpoint.
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 |
|---|---|---|---|
| Standard of Care Lipid Therapy | 2 | 43 | 4.7% |
| Aggressive Lipid Therapy | 3 | 44 | 6.8% |
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 |
|---|---|
| Standard of Care Lipid Therapy | 9 of 43 |
| Aggressive Lipid Therapy | 7 of 44 |
Most frequent serious adverse event terms
| Event term | Organ system | Standard of Care Lipid Therapy | Aggressive Lipid Therapy |
|---|---|---|---|
| Hospitalization | Cardiac disorders | 2 of 43 | 3 of 44 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Standard of Care Lipid Therapy | Aggressive Lipid Therapy |
|---|---|---|---|
| Periprocedural complications | Injury, poisoning and procedural complications | 1 of 43 | 3 of 44 |
| Creatine kinase-MB > 5x ULN | Renal and urinary disorders | 2 of 43 | 1 of 44 |
| Statin dose reduction | General disorders | 0 of 43 | 3 of 44 |
| Unplanned revascularization | Vascular disorders | 2 of 43 | 0 of 44 |
| Any bleeding | Blood and lymphatic system disorders | 2 of 43 | 0 of 44 |
| Creatine kinase-MB >10x ULN | Renal and urinary disorders | 2 of 43 | 0 of 44 |
| AST > 3x ULN | Hepatobiliary disorders | 0 of 43 | 0 of 44 |
| ALT > 3x ULN | Hepatobiliary disorders | 0 of 43 | 0 of 44 |
| Statin discontinuation | General disorders | 0 of 43 | 0 of 44 |
Serious events with the highest arm-level rate: hospitalization (6.8%).
The registry reports serious adverse events and other adverse events separately by treatment group. In the standard-of-care group, the serious-event count is 2 among 43 at risk, and the other-event count is 9 among 43 at risk. In the aggressive-therapy group, the serious-event count is 3 among 44 at risk, and the other-event count is 7 among 44 at risk. The registry also identifies hospitalization as a leading serious adverse-event term, at 6.8%.
These are descriptive counts in the registry record. They do not by themselves establish whether the groups differ in safety, and no statistical comparison or uncertainty interval for these counts is reported. The record does not define the event-collection window, provide event-level descriptions, or explain whether the counts refer to participants with events or total event occurrences. It also does not report a death count. The event counts should therefore be interpreted within the limits of the registry’s reporting, rather than treated as a comprehensive safety comparison.
12. What the Result Does, and Does Not, Mean
The registry describes a randomized comparison of aggressive and standard-of-care lipid-lowering therapy, with LCBI from near-infrared spectroscopy as the primary endpoint. Its focus is a change in an image-derived measure of yellow plaque content between baseline and 6–8 weeks after intervention. The endpoint description explains how the measure is constructed and identifies the median and interquartile range as the summary statistics.
What the record does not show is the numerical primary outcome by group or a defined between-group estimate. It therefore does not establish whether LCBI changed differently between the treatment groups, how large any difference was, or how precisely it was estimated. The missing comparison cannot be replaced by the trial title, the treatment descriptions, or a planned sample-size calculation. No conclusion about the effect of treatment on the primary endpoint follows from the endpoint definition alone.
The registry’s other listed outcomes cover imaging, physiology, cardiac enzymes, clinical events, and blood chemistry. Their inclusion shows the breadth of the outcomes being tracked, but the outcome names are not results. Likewise, the serious and other adverse-event counts provide limited descriptive safety information; without further definitions and a comparative analysis, they do not support a definitive safety contrast.
In general, a trial result is most informative when the treatment contrast, uncertainty, analysis population, and handling of missing data are clear. Several of those elements are not reported in the registry record. The findings should therefore be understood as an incompletely reported trial record: it identifies the scientific question and planned measurement, while leaving the principal numerical result and important analytic details unavailable.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it uses an imaging-derived endpoint rather than relying only on clinical events. The registry describes a chain from raw near-infrared spectroscopy signals to a probability of lipid core, a color representation, and finally an LCBI based on yellow pixels among viable pixels. That chain makes the endpoint concrete, while also highlighting why image acquisition and processing matter to the reliability of the final measurement.
The design also frames a useful statistical question: whether the measure changes differently between randomized groups over a stated follow-up interval. Repeated measurement creates choices about how baseline and follow-up values should be summarized and compared. Clear reporting of the contrast and its uncertainty is necessary to distinguish a within-group change from a between-group difference. The registry identifies the relevant time points and the descriptive summaries, but does not report the numerical comparison.
The record illustrates the importance of transparent accounting for endpoint availability. It notes that data could not be used for some participants because of follow-up loss and technical or data-integrity problems. Such missingness can affect both precision and the comparability of analyzed groups, especially when the reasons are related to measurement availability. Reporting the analysis population and sensitivity analyses would help readers assess this issue.
Finally, the discrepancy between the recorded enrollment and the enrollment described in the brief summary shows why planned and realized study counts should be distinguished. Planning assumptions do not replace observed results. Statistical interpretation depends on a coherent account of the endpoint, participants analyzed, treatment contrast, and uncertainty—details that are not all available in this registry 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 registry does not report the primary endpoint values by group, the between-group estimate, a confidence interval, or a p-value. Although it specifies LCBI at baseline and 6–8 weeks after intervention and identifies median and interquartile range summaries, the primary outcome is not reduced to one comparison. This prevents assessment of the direction, magnitude, or precision of the main treatment contrast.
The endpoint requires usable NIRS images. The record states that data were unavailable in 17 patients and lists loss to follow-up, image-formatting problems, equipment or catheter malfunction, and disc integrity or corruption among the reasons. It does not describe how missing values were handled, whether exclusions differed between groups, or whether sensitivity analyses were performed. This leaves uncertainty about the effect of endpoint availability on the analysis.
Other reporting gaps include the analysis population, the identity of the masked party, allocation-concealment procedures, the statistical model, and any multiplicity adjustment. Treatment descriptions also vary between the brief summary and arm descriptions, and the registry does not explain the relationship between the rosuvastatin dose range and the intensive-therapy description. The record does not provide detailed adherence or treatment-change information.
Enrollment is recorded as 87, while the brief summary describes a plan for 100 subjects, including 40 in each group. The discrepancy is not explained. The short stated endpoint window also means the primary measure addresses an early imaging outcome rather than long-term clinical events. These limitations concern what can be inferred from the registry record and do not establish what may have been reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy — NCT01567826.
- Registry record last updated 2017-05-19; status last verified 2017-04.
- Results first posted 2017-02-27.
- 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
NCT01567826 is a completed, randomized, single-masked, parallel-group phase 4 study of aggressive versus standard-of-care lipid-lowering therapy for coronary artery disease. The brief summary describes a single-site study. The registry records enrollment of 87 and lists study start as 2010-05 and primary completion as 2012-02. Its brief summary separately describes a plan for 100 subjects, with 40 assigned to each treatment group; the difference from the recorded enrollment is not explained.
The primary endpoint is Lipiscan LCBI, derived from NIRS, with baseline and 6–8-week assessments and median and interquartile range summaries. The registry describes missing endpoint data and lists 10 outcome measures and 2 analyses. It reports adverse-event counts by treatment group, but does not report a single numerical primary-outcome comparison or its uncertainty. Key details about the analysis population, missing-data methods, and statistical plan are not reported in the registry record.