Phase 2 Study in Vascular Inflammation on Patients After an Acute Coronary Syndrome Event: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study in Vascular Inflammation on Patients After an Acute Coronary Syndrome Event (NCT00552188), a randomized phase 2 study. The primary outcome is Change From Baseline in Plaque Imaging After 24 Weeks.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, parallel-group study of VIA-2291 and matching placebo in patients after an acute coronary syndrome event. The registry lists enrollment as 52 and describes the study as completed. The official title calls it double-blind, while the registry’s masking classification is quadruple. These are the registry’s descriptions; further details of who was masked are not reported in the registry record.

The primary outcome was a continuous imaging measure at baseline and 24 weeks. Its stated analysis population was the evaluable population, and its unit was TBR, the target (plaque) to background (blood) ratio. The posted arm summaries include 24 participants for VIA-2291 and 21 for placebo. These outcome counts differ from the enrollment figure, and the registry record does not explain the difference or give a detailed account of exclusions or missing outcome data.

The registry also lists a plaque-imaging outcome at 6 weeks. It reports two outcome measures and two analyses. The trial’s start and primary completion are recorded as 2007-10 and 2009-10. Further details about the randomization procedure, treatment adherence, allocation concealment, or the original statistical plan 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.

Before assignment: Subjects had Acute Coronory Syndrome (ACS) 1-3 months prior to randomization and must have received concomitant statin therapy for a minimum of 4 weeks and had a stable statin dose regimen for 2 weeks prior to randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable Population

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Plaque Imaging After 24 Weeks, measured over Baseline and 24 Weeks.

The primary endpoint is change from baseline in plaque imaging after 24 weeks, expressed as TBR. The description says PET imaging measured standardized FDG uptake in an index vessel, which could be the right carotid, left carotid, or ascending aorta. TBR compares uptake at the target plaque with background blood activity. The endpoint is therefore an imaging-based measure of vascular inflammation, rather than a count of heart attacks, deaths, or other clinical events.

Measuring change from baseline makes each participant’s later imaging result interpretable relative to that participant’s starting value. Comparing the changes between randomized groups is intended to assess whether the observed trajectory differs between VIA-2291 and placebo. The registry identifies the reported arm values as least-squares means and gives 95% confidence intervals. It describes the target population as evaluable, but does not report the detailed definition of evaluability.

As a general statistical point, an imaging endpoint can provide a quantitative measure of a biological process without establishing that a change in the image corresponds to a change in how patients feel, function, or experience clinical events. The registry record does not report evidence validating this particular change as a substitute for a clinical outcome.

7. Results Posted in the Registry

• VIA-2291: mean -0.01 versus -0.06 on control; difference 0.05 (95% CI -0.06 to 0.16), standardized effect d = 0.28; z-test p = 0.357.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Plaque Imaging After 6 Weeks

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • VIA-2291: mean 0.01 versus -0.07 on control; difference 0.08 (95% CI -0.03 to 0.19), standardized effect d = 0.44; z-test p = 0.139.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between VIA-2291 and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists one secondary outcome: change from baseline in plaque imaging after 6 weeks. The posted comparison is directionally positive for VIA-2291 relative to placebo, as is the primary comparison at 24 weeks. Both are imaging outcomes measured with TBR, but they concern different time points. The early result therefore provides a related observation, not an independent confirmation of the primary finding.

The reported ANCOVA p-value for the secondary outcome is 0.15, while the unadjusted recalculation gives p = 0.139. These values do not provide strong evidence of a group difference under the analyses reported. As with the primary endpoint, the registry does not give the adjusted contrast estimate or its confidence interval, limiting assessment of the sponsor’s model-based result. The recalculation is unadjusted and should not be treated as a substitute.

Secondary outcomes generally carry less confirmatory weight than a prespecified primary outcome, particularly when several outcomes or analyses are considered. Testing multiple outcomes increases the chance that at least one result appears notable by chance. The record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. The secondary finding should therefore be considered supportive and exploratory rather than decisive. Its broad direction is consistent with the primary contrast, but the uncertainty and the relationship between the imaging measures mean that it does not resolve the primary result’s imprecision.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Plaque Imaging After 6 Weeks

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s imaging change is represented numerically, rather than as an event count or a yes/no result. The registry reports least-squares means for the two arms and 95% confidence intervals. A least-squares mean is a model-based estimate; it can differ from a simple arithmetic average when the analysis adjusts for other variables. The registry does not give the adjusted arm estimates’ numerical values beyond the posted summaries, and it does not detail the model terms.

What does the ANCOVA analysis do?

The registry identifies the sponsor’s analysis as ANCOVA. In general, analysis of covariance compares groups on an outcome while accounting for one or more covariates, often including a baseline measure when the outcome is a change over time. Such adjustment can improve precision when the covariates are related to the outcome, but its result depends on the model and the analysis population. The registry record does not report the ANCOVA specification, the covariates included, or the adjusted treatment-effect estimate. It reports the analysis p-value as 0.34.

The registry’s p-value addresses how compatible the observed data are with a null hypothesis of no group difference, given the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result will replicate. A p-value alone also does not show the magnitude or precision of an effect. Here, the sponsor’s p-value is most informative when considered alongside the estimated arm changes and the confidence intervals.

What is the recalculated comparison?

The unadjusted recalculation contrasts the posted arm summaries. For the primary outcome, it gives a mean difference of 0.05 for VIA-2291 relative to placebo and an unadjusted p-value of 0.357. This calculation is a simple comparison of the posted summaries, not a reconstruction of the sponsor’s ANCOVA. The recalculation uses an approximate pooled standard deviation, as indicated in the analysis information. It should therefore be read as a check based on the posted summary statistics, not as a replacement for the trial’s reported model.

The recalculated confidence interval describes uncertainty around that unadjusted mean difference under its calculation assumptions. The interval includes no difference and also allows differences in either direction. In general, when an interval includes the null value, the data do not rule out no difference at the corresponding confidence level. That does not show that the true effect is exactly zero; it shows that the estimate is not precise enough to exclude a range of possibilities.

Why do the arm estimates and comparison both matter?

Each arm’s estimate gives the observed change within that group. The between-group contrast is the more direct quantity for the randomized treatment comparison because change in one arm alone cannot separate treatment-related change from time effects, measurement variability, or changes that might also occur under placebo. The group confidence intervals describe uncertainty around each arm estimate, while the comparison interval describes uncertainty around the difference. Overlap between arm intervals is not itself a formal test of the treatment contrast.

The primary reported analysis and the recalculation answer closely related but not identical statistical questions. ANCOVA is the sponsor’s named method; the recalculation is unadjusted. Their p-values are close, but one should not treat that closeness as proof that the methods are interchangeable. The registry record does not include enough model detail or adjusted estimates to reproduce the ANCOVA fully.

What does over-dispersion mean in general?

For continuous outcomes, variation among participants affects how precisely an average or group difference can be estimated. Greater variation relative to the effect makes it harder to distinguish a real group contrast from random fluctuation. General explanations of over-dispersion usually concern data whose variability exceeds what a particular model expects. This endpoint is continuous, and the registry does not report an over-dispersion assessment or a model diagnostic. It would not be appropriate to infer that such a problem was present.

More broadly, statistical conclusions depend on design, measurement, analysis population, missing data, and model assumptions as well as the calculated estimate. The registry record describes randomization and the outcome model label, but many details needed to assess those assumptions are not reported. The available numbers support a cautious reading of the estimated imaging contrast, rather than a claim that the analysis settles every uncertainty about the endpoint.

11. Confidence Intervals and Precision

The primary arm estimates are accompanied by 95% confidence intervals: -0.08 to 0.06 for VIA-2291 and -0.14 to 0.02 for placebo. Both intervals span zero. In practical terms, the posted arm estimates are uncertain, and the data are compatible with a range of changes around the point estimates. Those arm-specific intervals should not be mistaken for a confidence interval for the between-group contrast.

The recalculated difference is 0.05, with an unadjusted interval that extends from a negative value to a positive value. That interval includes no difference, so the recalculation does not precisely distinguish the groups. The registry’s ANCOVA result gives a p-value but does not report a numerical adjusted contrast or adjusted confidence interval. As a result, the precision of the sponsor’s adjusted treatment-effect estimate cannot be assessed directly from the posted analysis entry.

In general, a confidence interval is a range of values compatible with the data and the analysis assumptions at the stated confidence level. It is not a guarantee that the true value lies in the particular interval, nor does a wide interval mean that all values within it are equally plausible. Wider intervals indicate less precision. The observed outcome counts and the variation in the imaging measure are relevant to precision, but the record does not provide enough detail to attribute the uncertainty to any single cause.

The interval’s inclusion of zero should not be read as evidence of equivalence. Equivalence requires a prespecified margin and a design and analysis tailored to rule out differences larger than that margin. Such a margin or equivalence analysis is not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They illustrate sample sizes under the stated planning assumptions: a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect set to the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

For each effect assumption, the 80% power column gives the planned participants per arm for a design with an 80% chance of detecting that assumed effect if it is truly present, under the planning model and significance level. The 90% power column gives the corresponding planning target for a 90% chance. These are design calculations, not guarantees about a future study’s result. The values for 100% of the observed effect are 205 and 275 participants per arm; for 75% of the observed effect, 365 and 488; and for 50% of the observed effect, 820 and 1,098.

The observed effect is an uncertain estimate from a small study, so using it as a planning target can produce unstable illustrations. The table also makes clear that smaller assumed effects require more participants to detect, all else held constant. These figures are planning illustrations, not observed power. They do not establish what power the completed trial had, and they should not be read as the trial’s original enrollment target or as a recommendation about an appropriate future sample size.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.050; pooled standard deviation σ = 0.181.
2. n = 2 × (1.96 + 0.842)² × 0.181² / 0.050² = 205.0, rounded up to 205 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.05                      # observed difference in means
sigma <- 0.180686139211136                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(552188)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 205 (80% power), 275 (90% power)
 75% of observed effect: n per arm = 365 (80% power), 488 (90% power)
 50% of observed effect: n per arm = 820 (80% power), 1,098 (90% power)
power.t.test: 206 
Simulated power at n = 205 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s own primary analysis is ANCOVA and reports p = 0.34. The recalculation from the posted summary statistics is an unadjusted comparison, with a mean difference of 0.05 and p = 0.357. Their p-values lead to a similar broad reading: neither analysis gives strong evidence of a group difference on the primary imaging outcome. The recalculation is not a reproduction of the ANCOVA, because the registry does not provide the adjusted estimate, model details, or covariate set needed to recreate it.

The recalculation uses the reported arm summaries and an approximate pooled standard deviation. It is useful as a transparent check of the direction and rough scale of the contrast, but the sponsor’s specified analysis remains the primary reported analysis. The registry record indicates no discrepancy between the recalculation and reported result. Even so, agreement in broad interpretation does not erase the distinction between an adjusted model-based analysis and an unadjusted summary-based calculation.

The sponsor’s p-value alone does not quantify the treatment contrast or its precision. Because the registry does not give the ANCOVA estimate and confidence interval numerically, the adjusted effect’s size cannot be fully interpreted from the reported p-value alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and one secondary outcome, and it reports analyses for both. It does not report whether the study used a prespecified hierarchy, adjusted for multiple testing, or designated the secondary analysis as confirmatory. When multiple endpoints or repeated comparisons are tested, the chance of at least one apparently strong result can increase. In general, multiplicity procedures control or otherwise address that issue; without a reported plan, the secondary p-value should be interpreted cautiously.

The primary outcome description specifies an evaluable population, but a detailed definition is not reported in the registry record. The registry’s outcome arm counts are 24 for VIA-2291 and 21 for placebo, while enrollment is listed as 52. The record does not explain the movement from enrollment to the outcome analysis, report reasons for missing imaging, or describe how missing values were handled. It is therefore not possible to assess whether the evaluable analysis could be affected by differences between participants with and without a usable outcome.

The registry does not report an intention-to-treat analysis for this endpoint, a missing-data sensitivity analysis, or the number of participants who discontinued or were excluded from the primary analysis. These omissions do not show that the analysis was inappropriate; they limit what can be concluded about robustness. Missingness can matter if the likelihood of having an observed outcome is related to treatment assignment or to the outcome itself. Whether that occurred in this trial is not reported in the registry record.

The record also does not report interim analyses, a stopping rule, or the trial’s original statistical analysis plan. No assumptions about these design choices should be made from the posted results alone.

16. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (7.7%), angina pectoris (3.8%), atrial fibrillation (3.8%), in-stent coronary artery restenosis (3.8%), gastrointestinal haemorrhage (3.8%).

The registry reports serious adverse events affecting 5 participants in the VIA-2291 group and 5 in the placebo group, with 26 participants at risk in each group. These are counts of participants affected, not a comparison of event rates per unit of follow-up. The registry lists several serious-event terms, including unstable angina at 7.7%, and angina pectoris, atrial fibrillation, in-stent coronary artery restenosis, gastrointestinal haemorrhage, and melaena at 3.8% each. The listing does not by itself establish a causal relationship to study treatment.

Other adverse events affected 15 participants in the VIA-2291 group and 17 in the placebo group, with 26 at risk in each group. The registry record does not provide enough detail about event severity, timing, duration, or attribution to interpret those counts beyond their descriptive comparison. Deaths are not reported in the registry record.

Safety counts should be read alongside the study’s size, follow-up, and reporting definitions. Equal serious-event counts do not establish equal safety, and a numerical difference in other events does not establish a treatment effect. The registry’s adverse-event information is descriptive and does not replace a fuller safety analysis.

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

The posted results estimate a change in an imaging measure, not a change in clinical outcomes. The primary arm estimates and the unadjusted comparison suggest a less negative change in the VIA-2291 group than in the placebo group. However, the sponsor’s ANCOVA p-value is 0.34, the unadjusted p-value is 0.357, and the uncertainty around the estimated difference includes no difference. The evidence is therefore inconclusive about whether the groups differ on this endpoint.

That interpretation is not the same as saying that VIA-2291 has no effect. A study can yield an uncertain result because the estimate is imprecise, and the registry does not report an equivalence design or margin. Nor does a directionally different estimate establish a meaningful treatment effect. The reported contrast concerns the specified PET-based TBR measure among the evaluable population.

The study does not establish whether any imaging change corresponds to fewer clinical events, improved symptoms, or other patient-important outcomes. The registry’s posted results do not report such an outcome as the primary endpoint. The findings also cannot be generalized automatically beyond the studied population or follow-up period, particularly because detailed eligibility and missing-data information are not reported.

Overall, the record supports a cautious description: this randomized Phase 2 study produced an uncertain comparison on plaque imaging at 24 weeks, with a secondary imaging outcome measured at 6 weeks. It does not establish benefit, lack of benefit, equivalence, or a clinical effect. Further interpretation would require fuller outcome, analysis, and safety details than are reported in the registry.

18. Why This Trial Matters Statistically

This trial illustrates a central distinction in clinical statistics: an estimate’s direction is not the same as the strength of evidence for a difference. The VIA-2291 arm’s estimated change is less negative than the placebo arm’s, but the estimate is uncertain and the reported analysis does not provide strong evidence of a group contrast. Reading the point estimate together with its precision avoids over-interpreting a single number.

It also shows why the analysis method matters. The registry reports ANCOVA, while the recalculation compares posted summary statistics without adjustment. Those approaches are related but not identical. The sponsor’s p-value is the result of the reported analysis; a summary-based recalculation is a useful check but cannot replace model details that are absent from the record.

The distinction between an imaging endpoint and a clinical endpoint is equally important. A quantitative PET measure may help assess a biological process, but it does not by itself establish a change in clinical outcomes. The uncertain primary result, the secondary imaging result, and the descriptive adverse-event counts answer different questions and should not be blended into a single claim about treatment effect.

Finally, the record makes visible the importance of reporting the analysis population and missing outcomes. Enrollment and outcome counts are not the same, and the registry does not explain the difference. Without participant flow, model details, and missing-data analyses, readers have limited ability to judge how robust the result is. Those are statistical interpretation issues, not merely administrative details.

19. 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 record leaves important trial-specific uncertainties. Although it lists enrollment as 52, the primary outcome is posted for an evaluable population with arm counts of 24 and 21. Reasons for the difference, the evaluable-population definition, participant flow, and handling of missing imaging are not reported in the registry record. Those omissions limit assessment of selection and missing-data bias.

The sponsor’s primary method is identified as ANCOVA, but its covariates, model specification, adjusted effect estimate, and adjusted confidence interval are not reported. The posted p-value cannot convey the adjusted contrast’s scale or precision. The unadjusted recalculation cannot fill this gap because it is based on summary statistics and does not reproduce the sponsor’s model.

The endpoint is a PET imaging measure, and the record does not report whether changes in this measure are linked to clinical outcomes. Follow-up for the primary outcome is 24 weeks, so the reported result does not address longer-term imaging patterns or clinical events. The registry also does not report the original sample-size justification, interim analyses, or an analysis plan for multiplicity. These design and analysis details should not be inferred from the posted results.

The safety information is descriptive, and deaths are not reported in the registry record. The available adverse-event counts do not provide a complete account of event timing, severity, attribution, or exposure duration. Finally, the phase and enrollment indicate a Phase 2 study, but the registry record alone cannot establish how well the results generalize beyond the enrolled population.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Phase 2 Study in Vascular Inflammation on Patients After an Acute Coronary Syndrome Event — NCT00552188.
• Registry record last updated 2013-08-09; status last verified 2013-06.
• Results first posted 2013-08-09.
• 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.

23. Record Summary

NCT00552188 is a completed, randomized, parallel-group Phase 2 study of VIA-2291 versus matching placebo after an acute coronary syndrome event. Its primary outcome was change from baseline in plaque-imaging TBR at 24 weeks in the evaluable population. The registry reports least-squares mean changes of -0.01 for VIA-2291 and -0.06 for placebo, with an ANCOVA p-value of 0.34.

The unadjusted recalculation gives a mean difference of 0.05 and p = 0.357; it is not the sponsor’s adjusted analysis. The posted estimates are uncertain and do not establish a group difference. A secondary plaque-imaging outcome was recorded at 6 weeks, but it does not resolve that uncertainty. Missing-data details, the ANCOVA specification, and the original design assumptions are not reported in the registry record.