SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System (NCT00307047), a randomized phase 3 study. The primary outcome is Ischemia Driven Target Lesion Failure (TLF).

2. Clinical Question

The trial’s principal comparison asks whether the frequency of this composite endpoint differed between the randomized groups. The posted risk difference is expressed as TAXUS™ EXPRESS 2™ minus XIENCE V®; its positive value indicates a higher reported TLF percentage in the comparator group. The confidence interval and unadjusted p-value describe statistical uncertainty and compatibility with a no-difference value, respectively. They do not by themselves establish the clinical importance of the difference.

The question is specific to the endpoint definition, the participants included in the primary result, and the 1-year timeframe. It does not answer whether the devices differ for every possible outcome, over every timeframe, or in populations not represented by the trial. The registry record does not report the primary outcome population’s detailed eligibility criteria or how missing endpoint observations were handled.

3. Trial Design

The registry describes SPIRIT IV as a phase 3, randomized, single-masked, parallel-group clinical trial. Its recorded enrollment is 3687, and its status is completed. The listed start is 2006-08 and the listed primary completion is 2009-08. Abbott Medical Devices is named as the sponsor.

Participants were assigned to one of two active device groups: XIENCE V® everolimus-eluting coronary stent or TAXUS™ EXPRESS 2™ paclitaxel-eluting coronary stent. Random allocation is relevant because, in principle, it helps make groups comparable at the start with respect to measured and unmeasured characteristics. It does not guarantee that every feature will be balanced, and the allocation sequence and concealment procedures are not reported in the registry record.

The record identifies the study as single-masked, but it does not specify which people were masked or describe how masking was maintained. It also does not report details of the treatment procedure, the follow-up schedule, or whether outcome adjudication was independent of treatment assignment. Those omissions limit how much can be inferred about implementation from the registry description alone.

The posted primary endpoint is a binary outcome, reported as a percentage of participants with TLF at 1 year. The primary result lists 2416.0 participants for XIENCE V® and 1195.0 for TAXUS™ EXPRESS 2™. The denominator counts used in the posted comparison are also identified, but the registry record does not explain why those analysis counts differ from the recorded enrollment or specify the analysis population definition.

Secondary outcomes include ischemia driven target vessel failure and revascularization outcomes. The posted secondary results described in the record include 30-day assessments. Although the registry lists 65 secondary outcomes, the outcome descriptions do not by themselves establish which outcomes were prespecified as key or how they were prioritized in the trial’s analysis. That statistical plan is 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: Patients who met inclusion/exclusion criteria were offered participation in the study, and randomized until the total trial population was reached.

Overall Study

Reasons for not completing this period:

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 Ischemia Driven Target Lesion Failure (TLF), measured over 1 year.

The primary endpoint is the percentage of participants with ischemia driven target lesion failure (TLF) at 1 year. The registry defines TLF as a composite of cardiac death, target vessel myocardial infarction, and ischemia driven target lesion revascularization (TLR). A participant meeting the endpoint through any component contributes to the composite result; the posted overall percentage does not reveal how much each component contributes.

Composite outcomes are used to combine clinically relevant events into a single measure. This can capture more than one way a treatment course may result in an unfavorable outcome, while making the primary comparison more focused than a separate primary test for every component. The trade-off is that components may differ in seriousness, frequency, and interpretation. A composite percentage therefore should not be read as if every included event were equivalent or as a direct estimate for any individual component.

The ischemia driven qualification is part of the registry’s endpoint definition. The record does not provide additional adjudication criteria or the component-specific primary results. The 1-year timeframe means the posted result describes the endpoint over that specified period; it does not establish what happened after that period.

The primary result is reported as a percentage of participants rather than as a time-to-event measure. The registry does not report a hazard ratio or explain whether any other primary analysis was conducted. Interpretation should therefore remain tied to the reported participant percentages and their risk-difference comparison.

7. Results Posted in the Registry

• TAXUS™ EXPRESS 2™: 6.8% (81/1195) versus 4.2% (101/2416) on control; risk difference 2.6 percentage points (95% CI 1.0 to 4.2), risk ratio 1.62 (1.22–2.15); unadjusted two-proportion z-test p = <0.001.

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.

Ischemia Driven Target Vessel Failure (TVF)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • TAXUS™ EXPRESS 2™: 3.1% (38/1222) versus 1.9% (47/2451) on control; risk difference 1.2 percentage points (95% CI 0.1 to 2.3), risk ratio 1.62 (1.06–2.47); unadjusted two-proportion z-test p = 0.024.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for TAXUS™ EXPRESS 2™ than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Ischemia Driven Target Lesion Revascularization (TLR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • TAXUS™ EXPRESS 2™: 1.1% (13/1222) versus 0.4% (10/2451) on control; risk difference 0.7 percentage points (95% CI 0.0 to 1.3), risk ratio 2.61 (1.15–5.93); unadjusted two-proportion z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for TAXUS™ EXPRESS 2™ than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Ischemia Driven Target Vessel Revascularization (TVR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • TAXUS™ EXPRESS 2™: 1.6% (20/1222) versus 0.7% (17/2451) on control; risk difference 0.9 percentage points (95% CI 0.2 to 1.7), risk ratio 2.36 (1.24–4.49); unadjusted two-proportion z-test p = 0.007.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for TAXUS™ EXPRESS 2™ than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results concern target vessel failure, target lesion revascularization, and target vessel revascularization at 30 days. For each, the observed percentage was higher in the TAXUS™ EXPRESS 2™ group than in the XIENCE V® group. This direction is broadly consistent with the primary comparison’s direction, but the secondary endpoints are not interchangeable with TLF and were assessed over a different timeframe.

The primary endpoint combines cardiac death, target vessel myocardial infarction, and ischemia driven target lesion revascularization at 1 year. The secondary results cover specific failure or revascularization outcomes at 30 days. Similar directions across these measures can provide descriptive context, but they do not establish that the primary composite’s result is driven by any particular component. The registry record does not provide component-specific primary results in the information reported for this trial.

The registry reports 65 secondary outcomes. When many secondary outcomes are tested, separate unadjusted p-values do not account for the increased chance of finding apparently noteworthy results through repeated testing. The registry record does not report a multiplicity adjustment or a hierarchy that would identify which secondary results were intended to support confirmatory conclusions. Consequently, the secondary findings carry less evidential weight than the designated primary comparison and should be read as exploratory or descriptive unless the trial’s analysis plan establishes otherwise; that plan is not reported in the registry record.

The secondary results also have their own denominators and event counts, which differ from those in the primary result. Those figures should be interpreted outcome by outcome rather than treated as a common analysis population. The record does not explain why denominators vary or whether missing observations were handled consistently across endpoints. Together, the observed direction, outcome definitions, timeframes, multiplicity, and reporting gaps all matter when relating secondary findings to the primary result.

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

• Ischemia Driven Target Vessel Failure (TVF)
• Ischemia Driven Target Vessel Failure (TVF)
• Ischemia Driven Target Vessel Failure (TVF)
• Ischemia Driven Target Vessel Failure (TVF)
• Ischemia Driven Target Vessel Failure (TVF)
• Ischemia Driven Target Vessel Failure (TVF)
• Ischemia Driven Target Lesion Revascularization (TLR)
• Ischemia Driven Target Lesion Revascularization (TLR)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant either met the registry’s TLF definition during the stated timeframe or did not. The reported percentages express the proportion of participants with the event in each group. For this kind of outcome, a risk difference directly compares the two proportions. In the posted comparison, the contrast is TAXUS™ EXPRESS 2™ minus XIENCE V®, so a positive risk difference means the event proportion is higher in the former group.

What does the risk difference express?

The primary risk difference is 0.026. It is an absolute contrast on the proportion scale, not a relative ratio. Absolute contrasts retain the scale of the event frequency and can be read alongside the two group percentages. A risk difference does not indicate which component of a composite endpoint accounts for the contrast, and it does not describe how an individual participant’s outcome would change.

The record also includes relative measures for the primary comparison: a risk ratio of 1.621 with an interval from 1.221 to 2.154, and an odds ratio of 1.667 with an interval from 1.233 to 2.252. A risk ratio compares proportions as a ratio; an odds ratio compares odds, which are distinct from probabilities. These measures answer different numerical questions from the risk difference and can appear farther from one than the absolute comparison might suggest, particularly when readers are unfamiliar with the odds scale. The risk difference is the clearest expression of the absolute contrast in the posted comparison.

How should the confidence interval be understood?

A confidence interval conveys uncertainty around an estimate. In general, repeated use of the same method under its assumptions would produce intervals that include the underlying value at the stated confidence level at the corresponding long-run rate. It is not a range containing a fixed proportion of individual participant outcomes, and it is not a probability statement about the true value after observing these data. The primary interval extends from 0.010 to 0.042. Its endpoints describe values compatible with the estimate under the interval method and its assumptions; they do not capture every possible source of bias or uncertainty.

The interval lies above zero, the no-difference value for a risk difference. That is consistent with the small unadjusted p-value of <0.001. A p-value is calculated under a null model and summarizes how unusual data at least as incompatible with that model would be if the model and test assumptions held. It is not the probability that the observed result arose by chance, and it does not establish that the effect is important in clinical terms. The registry does not report whether the comparison was adjusted for other variables or whether the p-value belongs to a broader testing strategy.

Why do denominators and endpoint definitions matter?

The primary endpoint is defined as a composite of cardiac death, target vessel myocardial infarction, and ischemia driven TLR. The posted comparison uses event counts of 101 and 81 and analysis denominators of 2416.0 and 1195.0, respectively. These denominators are the relevant group sizes for interpreting the posted comparison, rather than the overall enrollment figure. The registry record does not explain the analysis population or the reasons for the difference between enrollment and endpoint denominators.

For binary outcomes, an analysis may be affected by how missing endpoint values are treated, whether participants are analyzed according to randomized assignment, and whether follow-up differs between groups. Such choices can affect estimated percentages and uncertainty. The missing-data approach, analysis population definition, and details of follow-up for the primary endpoint are not reported in the registry record. They should not be assumed from the randomized label alone.

What does an unadjusted comparison leave out?

An unadjusted comparison contrasts the observed group results without an adjustment in the reported estimate for other measured factors. In a randomized design, randomization is intended to support group comparability, but chance imbalances can still occur. Adjustment may be useful under a prespecified analysis plan, but the registry record does not report a model, adjustment variables, or a primary analysis specification. The posted comparison should therefore be read as an unadjusted statistical contrast, not as evidence about an unreported adjusted model.

Multiplicity is another consideration. When many outcomes or comparisons are examined, the chance of at least one small p-value can increase if each is tested separately without accounting for the family of tests. The record lists 65 secondary outcomes, while the provided secondary summaries include multiple outcomes. It does not report multiplicity control, a hierarchy of tests, or which secondary comparisons were designated confirmatory. As a result, the unadjusted secondary p-values provide less confirmatory evidence than a single prespecified primary comparison would.

Finally, a statistically detectable difference and a clinically meaningful difference are not interchangeable concepts. Statistical significance reflects the estimate relative to its uncertainty under a test, while clinical importance requires a judgment about consequences and context. A threshold for clinical importance is not reported in the registry record. The posted event proportions, risk difference, confidence interval, and endpoint definition should be considered together, without extending the result beyond the trial’s stated population and timeframe.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.026, and its confidence interval runs from 0.010 to 0.042. The interval excludes zero and is entirely on the side indicating a higher observed TLF percentage in TAXUS™ EXPRESS 2™ relative to XIENCE V®. This gives a range of values compatible with the data under the interval method, rather than a guarantee that the true contrast lies within those endpoints.

The interval has a lower endpoint relatively near zero compared with its upper endpoint, so the evidence is compatible with a range of positive differences rather than a single exact contrast. Precision is not the same as absence of bias: a confidence interval can quantify sampling uncertainty without accounting for incomplete follow-up, endpoint misclassification, or other limitations. The registry record does not report enough detail to assess all such sources of uncertainty.

The group percentages are rounded to 4.2% and 6.8%. The comparison uses the event counts and denominators posted for the primary analysis, so calculations from the rounded percentages may not reproduce its estimate or interval. The counts and analysis denominators are 101 of 2416.0 for XIENCE V® and 81 of 1195.0 for TAXUS™ EXPRESS 2™.

Precision also depends on the number of observed events and the analysis method, not just on the total enrolled. The registry record does not provide a precision target or clinical threshold against which to judge whether this interval is sufficiently narrow. It is therefore most useful to describe the estimate and interval directly and to distinguish statistical uncertainty from uncertainty about generalizability, clinical importance, and the handling of missing data.

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 illustrations based on the observed effect, not the trial’s own original design assumptions. The registry record does not report the original sample-size justification or the assumptions used to plan SPIRIT IV. For the posted planning illustration, the assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect.

For these binary outcomes, the planning figures are participants per arm, not total events. The 80% power column describes the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the chosen effect under its assumptions, if that effect were the true one. The 90% power column uses a higher chance of detection and therefore gives a larger required number for the same assumed effect.

Rows for planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect show how the required group size changes as the target effect changes. Smaller effects are harder to distinguish from random variation, so the illustration requires more participants per arm for smaller effects. These figures are planning scenarios, not a statement about what the completed trial actually had the power to detect. This is not observed power.

The calculation assumes equal allocation, whereas the posted primary analysis denominators are not equal. The illustration’s assumptions should therefore be understood on their own terms and not mistaken for a reconstruction of the trial’s design or analysis. The registry record does not report whether the original plan used other assumptions, whether there were interim analyses, or whether sample-size planning addressed a different endpoint or analysis population.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.042; treatment proportion p₁ = 0.068; average p̄ = 0.055.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3218 = 0.6308.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3213 = 0.2704.
4. n = (0.6308 + 0.2704)² / (0.0260)² = 1,203.5, rounded up to 1,204 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
p0 <- 0.0418046357615894                          # control proportion
p1 <- 0.0677824267782427                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(307047)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,204 (80% power), 1,611 (90% power)
 75% of observed effect: n per arm = 2,021 (80% power), 2,705 (90% power)
 50% of observed effect: n per arm = 4,276 (80% power), 5,724 (90% power)
power.prop.test: 1203.5 
Simulated power at n = 1,204 per arm: 0.809 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

The registry record lists 65 secondary outcomes, but it does not report a multiplicity strategy. It is not reported in the registry record whether a hierarchy of primary and secondary hypotheses was prespecified, whether family-wise error or another error rate was controlled, or whether any secondary outcomes were intended as confirmatory. Without that information, the posted unadjusted secondary p-values should not be treated as if each were an isolated, prespecified test with no testing context.

Multiplicity matters because testing many outcomes creates more opportunities for a small p-value to occur even when there is no underlying difference for the outcomes considered. Adjustments or an ordered testing plan can address aspects of this issue, but the record does not say whether either approach was used. This uncertainty does not erase the reported estimates; it limits the strength of confirmatory claims that can be based on secondary p-values alone.

The registry record does not report the missing-data method for the primary or secondary outcomes, including whether participants without an observed outcome were excluded, imputed, or treated in another way. It also does not report the analysis population definitions, the treatment of protocol deviations, or whether the primary comparison followed randomized assignment. These details are important because exclusions and missing observations can affect both group percentages and the comparability intended by randomization.

Denominators vary between outcomes and differ from the recorded enrollment. That difference is visible in the posted results, but the reason is not reported in the registry record. It should not be assumed to reflect a particular eligibility rule, follow-up loss, or analytic choice. The record also does not report interim analyses or stopping rules. These are gaps in the available statistical description, not evidence that a specific procedure was or was not used.

15. 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 pectoris (12.6%), arrhythmia (3.5%), myocardial infarction (3.5%), non-cardiac chest pain (2.3%), chest pain (2.0%).

The registry reports serious adverse events for each device group, with a serious-event risk denominator of 2436 for XIENCE V® and 1214 for TAXUS™ EXPRESS 2™. The corresponding number of participants affected is 913 and 468. Other adverse events are listed with the same respective risk denominators, and affected counts of 762 and 407. These figures describe the posted event reporting and should not be confused with the primary TLF outcome, which has its own definition and analysis denominators.

The registry lists angina pectoris at 12.6%, arrhythmia at 3.5%, myocardial infarction at 3.5%, non-cardiac chest pain at 2.3%, chest pain at 2.0%, and pneumonia at 2.0% among the serious-event terms. The listed terms do not give a group-specific breakdown in this summary, so they should not be attributed to one device group. The record does not report death counts in the adverse-event summary.

Adverse-event counts alone do not establish whether one device has a more favorable safety profile. Interpretation would require attention to event definitions, follow-up, participant-level overlap, severity, and comparative analyses, details that are not fully reported in the registry record. The figures are descriptive safety information, not advice about treatment.

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

The posted primary data show a higher percentage of TLF at 1 year in the TAXUS™ EXPRESS 2™ group than in the XIENCE V® group: 6.8% compared with 4.2%. The risk-difference estimate is 0.026, with an interval from 0.010 to 0.042 and an unadjusted p-value of <0.001. These statistics describe the observed comparison and its sampling uncertainty under the analysis assumptions.

The result does not state that every participant in one group had a worse outcome or that the same contrast would apply to every patient or clinical setting. It does not identify which TLF component accounts for the group percentages, because component-specific primary results are not reported in the registry record. Nor does the result establish effects beyond the 1-year primary timeframe.

The finding also does not, by itself, determine clinical importance. Statistical evidence against a no-difference model is not the same as evidence that a difference is large enough to matter to patients or clinicians. The registry record does not report a clinical importance threshold or enough context to make that judgment. The adverse-event summaries provide descriptive information, but they do not supply a complete, adjusted assessment of comparative benefit and harm.

Random assignment supports a comparison between the groups, but it does not remove uncertainty about missing data, endpoint ascertainment, analysis populations, and generalizability. Those aspects are not fully described in the registry record. The result should therefore be understood as evidence about the posted endpoint in the trial population and follow-up period, rather than a universal claim about stent treatment or all outcomes.

Finally, secondary outcomes point in a similar observed direction at 30 days, but their multiplicity context is not reported. They add descriptive context rather than replacing the primary endpoint or independently resolving the limits of the evidence. The posted data are most informative when the endpoint definition, comparison direction, confidence interval, and reporting gaps are considered together.

17. Why This Trial Matters Statistically

SPIRIT IV illustrates why a clinical trial result should be read through the endpoint definition and the scale of the comparison, not only through a p-value. TLF is a composite of cardiac death, target vessel myocardial infarction, and ischemia driven TLR. Its overall percentage gives a concise primary outcome, while leaving open how the components contributed. That distinction is important whenever a composite combines different kinds of events.

The risk difference communicates an absolute contrast, while the registry also supplies relative measures. These express different aspects of the same comparison and should not be confused. The confidence interval adds information about precision that a p-value alone cannot provide. Together, the estimate and interval show both the direction and the range of statistical uncertainty represented by the posted analysis.

The trial also highlights the distinction between an assigned treatment comparison and a fully documented analysis. The record identifies randomization and reports endpoint denominators, but does not explain the analysis populations or missing-data handling. Without those details, readers cannot fully evaluate how the recorded enrollment relates to the endpoint analysis or how exclusions may have affected the comparison.

Finally, the number of secondary outcomes makes multiplicity relevant. Results that align in direction with the primary finding can be informative, but unadjusted secondary tests carry less weight when no testing hierarchy or multiplicity method is reported. The trial is therefore a useful example of reading primary and secondary evidence separately, interpreting uncertainty on the correct scale, and distinguishing what posted data show from what the registry record does not report.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations are specific to the information reported for this trial. The recorded enrollment is 3687, while the primary analysis denominators are 2416.0 for XIENCE V® and 1195.0 for TAXUS™ EXPRESS 2™. The registry record does not explain the difference or define the endpoint analysis population. Without that explanation, the reasons for the analyzed denominators cannot be inferred.

The primary endpoint is a composite, but component-specific primary results are not reported in the registry record. It is therefore not possible from these results alone to determine how cardiac death, target vessel myocardial infarction, and ischemia driven TLR each contributed to the overall percentage. The record also does not report detailed outcome adjudication criteria or the handling of missing endpoint data.

Although the record describes randomization and single masking, it does not specify who was masked, how allocation was concealed, or whether outcome assessors were masked. It does not report a detailed statistical analysis plan, the original sample-size justification, interim analyses, or stopping rules. These gaps limit assessment of design and analysis decisions; they do not show that a particular procedure was absent.

The registry lists 65 secondary outcomes, but the multiplicity approach and any hierarchy of secondary hypotheses are not reported. The available unadjusted secondary results should therefore be interpreted cautiously. The adverse-event summary also does not provide a group-specific breakdown for the listed serious-event terms, and death counts are not reported in that summary.

Finally, the registry record provides limited detail about participant characteristics, eligibility criteria, follow-up completeness, and treatment procedures. Those gaps constrain evaluation of how broadly the trial results apply. The record does not support extending the 1-year primary result to later timeframes, different populations, or outcomes that were not reported.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System — NCT00307047.
• Registry record last updated 2012-11-07; status last verified 2012-10.
• Results first posted 2010-10-21.
• 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.

22. Record Summary

SPIRIT IV, registry identifier NCT00307047, is recorded as a completed phase 3 randomized, single-masked, parallel-group trial sponsored by Abbott Medical Devices. The recorded enrollment is 3687; the listed start is 2006-08 and primary completion is 2009-08.

The trial compared XIENCE V® everolimus-eluting coronary stents with TAXUS™ EXPRESS 2™ paclitaxel-eluting coronary stents. Its primary endpoint was the percentage of participants with ischemia driven TLF at 1 year, a composite of cardiac death, target vessel myocardial infarction, and ischemia driven TLR.

The posted primary percentages were 4.2% for XIENCE V® and 6.8% for TAXUS™ EXPRESS 2™. The risk difference, oriented as TAXUS™ EXPRESS 2™ minus XIENCE V®, was 0.026, with a confidence interval from 0.010 to 0.042 and an unadjusted p-value of <0.001. The registry also reports 30-day secondary outcomes and adverse-event counts. Details about the primary analysis population, missing-data handling, multiplicity procedures, and original design assumptions are not reported in the registry record.