Bivalirudin Infusion for Ventricular Infarction Limitation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bivalirudin Infusion for Ventricular Infarction Limitation (NCT02565147), a randomized phase 3 study. The primary outcome is CMR Assessment Of Infarct Size At Day 5.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel Phase 3 study sponsored by The Medicines Company. The condition is acute myocardial infarction. Enrollment is recorded as 78. The study start date is 2014-12-19, primary completion is recorded as 2016-06-14, and the status is terminated. The reason for termination and the timing or circumstances of that decision are not reported in the registry record.

Both arms received PPCI, with bivalirudin in one arm and heparin in the other. The registry describes the bivalirudin regimen as a bolus and infusion during PPCI, with the infusion continuing for the first 4 h after completion. In the heparin arm, UFH was given as a bolus according to site standard of care; an ACT of 250 s or more at the end of the procedure was recommended. The record does not describe additional treatment procedures beyond these details.

Randomization indicates that assignment was intended to be made by chance, but the method used to generate or implement the allocation is not reported in the registry record. Single masking is recorded, but the identity of the masked party is not reported. The allocation ratio, eligibility criteria beyond the primary endpoint population description, and the trial’s original statistical design assumptions are also not reported in the registry record.

The primary endpoint analysis used a per-protocol population: participants who had successful PPCI and CMR without major protocol deviations. The endpoint was infarct size at Day 5. This population definition matters when relating the posted endpoint counts to the enrollment figure: the primary results are not reported for every enrolled participant. The registry status and enrollment alone do not establish why the study ended or whether it reached its planned enrollment.

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: Enrolled participants who underwent successful primary percutaneous coronary intervention (PPCI) defined as thrombolysis in myocardial infarction (TIMI) Flow of 2 or 3, underwent cardiac magnetic resonance imaging (CMR) at 5 days, and were without major protocol deviations were included in the per-protocol population (primary/secondary analyses).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol 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.

Population: Safety Population included all enrolled participants who received either bivalirudin or UFH.

6. Primary Endpoint

The registry lists the primary outcome as CMR Assessment Of Infarct Size At Day 5, measured over 5 days post PPCI.

The primary endpoint was cardiac infarct size assessed by CMR at Day 5, expressed in grams. The registry describes infarct size as the amount of cardiac injury and identifies CMR as a method that has improved the accuracy of infarct-size estimation; it characterizes CMR as the current gold standard for that assessment. The endpoint therefore captures a measured feature of heart-muscle injury after the procedure, rather than a clinical event such as death.

The posted group summaries are means with standard deviations. For participants in the per-protocol population, the mean infarct size was 25.0 grams in the bivalirudin arm and 27.1 grams in the heparin arm. The standard deviations were 19.7 and 20.7 grams, respectively. A mean gives the average measurement within a group; the standard deviation describes how dispersed individual measurements were around that group mean. It is not the uncertainty interval for the mean.

CMR measurement can provide a quantitative endpoint for comparing infarct size between groups. A Day 5 measurement is a snapshot at the specified time point, however, and does not alone describe later function, symptoms, or other outcomes. The registry’s endpoint definition also restricts the analysis to participants who completed successful PPCI and CMR without major protocol deviations. The reasons for that restriction and the handling of participants outside this population are not reported in the registry record.

7. Results Posted in the Registry

• PPCI With Heparin: mean 27.10 versus 25.00 on control; difference 2.10 (95% CI -7.85 to 12.05), standardized effect d = 0.10; z-test p = 0.679.

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.

CMR Assessment Of Myocardial Salvage Index (MSI) At Day 5

• 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:
  • PPCI With Heparin: mean 51.20 versus 39.40 on control; difference 11.80 (95% CI -3.69 to 27.29), standardized effect d = 0.57; z-test p = 0.135.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PPCI With Heparin and the control. The interval gives the range of effects that remain compatible with the data.

CMR Assessment Of Left Ventricular Ejection Fraction (LVEF) At Day 5

• 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:
  • PPCI With Heparin: mean 48.60 versus 48.50 on control; difference 0.10 (95% CI -5.31 to 5.51), standardized effect d = 0.01; z-test p = 0.971.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PPCI With Heparin and the control. The interval gives the range of effects that remain compatible with the data.

CMR Assessment Of LVEF At Day 90

• 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:
  • PPCI With Heparin: mean 49.10 versus 54.60 on control; difference -5.50 (95% CI -12.17 to 1.17), standardized effect d = -0.46; z-test p = 0.106.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PPCI With Heparin and the control. The interval gives the range of effects that remain compatible with the data.

The numerical secondary results span different aspects of cardiac injury and function, and they do not form a single consistent pattern across time and measure. The Day 5 myocardial salvage index is numerically higher in the heparin arm, the Day 5 LVEF means are nearly alike, and the Day 90 LVEF mean is numerically higher in the bivalirudin arm. The unadjusted intervals for these numerical comparisons include zero. In broad terms, the secondary results do not resolve the uncertainty in the primary endpoint or establish a consistent advantage for either arm.

The registry lists additional secondary outcomes, including CMR assessment of micro-vascular obstruction, flow and myocardial blush at the end of PPCI, in-hospital net adverse cardiac events at Day 5, and death at Day 90. Numerical results for these outcomes are not reported in the registry record. Their absence means they cannot be used to confirm, contradict, or extend the pattern in the posted quantitative results.

Secondary outcomes generally carry less weight than a prespecified primary outcome when many outcomes are examined. Each additional comparison creates more opportunity for an apparently notable result to arise by chance, particularly when results are interpreted without adjustment for multiplicity. The registry record does not report whether a multiplicity strategy was planned or applied. The secondary comparisons should therefore be treated as exploratory descriptions rather than independent confirmation of the primary finding.

The measures also differ in their meaning and timing: an imaging index, ventricular function, procedural flow measures, adverse events, and death are not interchangeable outcomes. The registry’s listed secondary outcomes could contribute complementary information, but missing numerical results and the absence of reported multiplicity details limit an integrated interpretation. The secondary record is thus incomplete for judging the full set of intended outcomes.

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

• CMR Assessment Of Myocardial Salvage Index (MSI) At Day 5
• CMR Assessment Of Micro-vascular Obstruction (MVO) At Day 5
• CMR Assessment Of Left Ventricular Ejection Fraction (LVEF) At Day 5
• CMR Assessment Of LVEF At Day 90
• TIMI Flow And Myocardial Blush Grade (MBG) At End Of PPCI
• Percentage of Participants With In-Hospital Net Adverse Cardiac Events (NACE) At Day 5
• Death At Day 90

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: infarct size is measured in grams, and the registry reports a mean and standard deviation for each arm. A mean difference compares the average outcome in one group with the average in the other. In the recalculation, the contrast is expressed as heparin minus bivalirudin. A positive estimate therefore means the observed mean is higher in the heparin arm, while a negative estimate would mean it is higher in the bivalirudin arm. This direction describes the arithmetic contrast; it does not establish a treatment effect.

What do the mean and standard deviation describe?

The mean is the arithmetic average of the measurements in a group. The standard deviation describes the spread of individual measurements around that average. It is not a confidence interval and does not show how precisely the group mean has been estimated. In the primary results, the means are 25.0 and 27.1 grams, while the standard deviations are 19.7 and 20.7 grams. The broad spread relative to the mean contrast helps explain why a modest difference between averages can be estimated with substantial uncertainty.

A mean-based comparison is informative when the scientific question concerns average infarct size. It can be sensitive to unusually large or small observations, particularly when a sample is limited or the outcome distribution is skewed. The registry does not report distributional diagnostics or the data-level details needed to assess those features. The recalculation uses posted summary statistics, so it cannot reproduce analyses that depend on individual observations.

Why is the registry test different from the recalculation?

The registry reports a Wilcoxon Rank Sum Test for superiority. In general, this test ranks observations from both groups and evaluates whether the rank distributions differ; it does not directly estimate the difference between arithmetic means. It can be useful when a rank-based comparison is appropriate, but interpretation depends on distributional features and on the estimand intended by the analysis. The registry record does not report the underlying ranks, test statistic, or a rank-based effect estimate and confidence interval.

The recalculated result instead compares the posted means using an unadjusted mean-difference approach. Its point estimate is 2.1 grams, its interval is -7.848 to 12.05 grams, and its unadjusted p-value is 0.679. Because the statistical methods and target summaries differ, the recalculated p-value need not match the registry’s Wilcoxon p-value. The two analyses should be read as distinct summaries, not as a correction of one another.

How should a p-value be understood?

In general, a p-value measures how unusual results at least as incompatible with a specified null hypothesis would be if that hypothesis and the test’s assumptions were correct. It is not the probability that the null hypothesis is true, nor the probability that the observed result is due to chance. A p-value also does not measure the size or clinical importance of a difference. Here, the registry reports a rank-based p-value, while the mean-based recalculation reports an unadjusted p-value. The original statistical analysis plan and any adjustment strategy are not reported in the registry record.

The sample-size planning assumptions mention a two-sided significance level of 0.05 for the planning illustration. That assumption belongs to the illustration, not necessarily to the trial’s original design. The original significance level, sidedness, and other analysis details are not reported in the registry record. The planning assumption should therefore not be used to infer that the primary analysis followed the same threshold or that it was prespecified in that form.

What does the confidence interval add?

In general, a confidence interval represents uncertainty around an estimate under a statistical procedure and its assumptions. It gives a range of values compatible with the data and that procedure, rather than a list of values that are equally likely or a guarantee that the true value lies inside the particular interval. The primary mean-difference interval extends from -7.848 to 12.05 grams. Because it includes zero, the summary is compatible with no mean difference; because it also extends to values on either side, it does not establish that any difference must favor one arm. The confidence level and construction method for the registry’s own Wilcoxon analysis are not reported.

The recalculation is unadjusted and based on posted summary statistics. It does not account for possible covariates, missing outcomes, clustering, or other design features unless those are represented in the posted aggregate data; the registry record does not report such adjustments for the primary analysis. It should be understood as a transparent summary calculation, not a substitute for the sponsor’s analysis of participant-level data.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 2.1 grams for heparin minus bivalirudin. Its interval runs from -7.848 to 12.05 grams. The interval includes zero and extends in both directions, so the data do not identify a precise direction for the difference in group means. It is compatible with a lower mean in the heparin arm, no mean difference, or a higher mean in that arm under the recalculation’s method.

The interval is wide relative to the point estimate. That width reflects uncertainty in estimating the contrast from the posted sample summaries; it should not be confused with the spread of individual observations, which is described by the group standard deviations. The primary standard deviations are 19.7 grams in the bivalirudin arm and 20.7 grams in the heparin arm. The per-protocol group counts are 28 and 36. Those counts and the observed variability help contextualize the limited precision without implying that the result is uninformative.

The registry does not report a confidence interval for its Wilcoxon Rank Sum Test. The mean-difference interval therefore pertains to the recalculated mean comparison, not to the rank-based test. The confidence level for the recalculated interval is not stated in the registry record, so it should not be assigned a confidence level based on assumption. Likewise, the record does not state a threshold for a clinically important difference. Statistical uncertainty can be described, but clinical importance cannot be decided from the interval alone.

The interval should not be read as proof of equivalence or as evidence that meaningful differences have been excluded. Establishing equivalence or non-inferiority would require a prespecified margin and an analysis designed for that question; such a margin is not reported in the registry record. The broad interval leaves substantial uncertainty about the size and direction of the mean contrast.

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 participants and not total events. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its reference and considers planning for 100%, 75%, or 50% of that observed effect. These are illustration assumptions; the trial’s own original design assumptions are not reported in the registry record.

For planning around 100% of the observed primary effect, the illustration gives 1,463 participants per arm for 80% power and 1,959 participants per arm for 90% power. For 75% of the observed effect, it gives 2,601 participants per arm for 80% power and 3,481 participants per arm for 90% power. For 50% of the observed effect, it gives 5,851 participants per arm for 80% power and 7,833 participants per arm for 90% power.

In plain terms, 80% power means that, under the planning assumptions and for the specified effect, a study of that size would have an 80% chance of rejecting the null hypothesis if that effect were the true one. The 90% column describes the corresponding planning target with a higher chance of detecting that specified effect. Neither figure is a prediction that a particular trial will succeed. This is not observed power.

The illustration shows the general relationship between effect size and required enrollment: smaller effects require more participants to detect with the same power under otherwise unchanged assumptions. Since the observed primary difference is small relative to the variation, the planning figures based on that observed difference are large. They are not a reconstruction of the original trial’s intended enrollment, nor evidence about why the study was terminated. The registry does not report the original sample-size justification or any original target enrollment.

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 = 2.100; pooled standard deviation σ = 20.271.
2. n = 2 × (1.96 + 0.842)² × 20.271² / 2.100² = 1,462.6, rounded up to 1,463 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 <- 2.1                      # observed difference in means
sigma <- 20.270580939206                     # 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(2565147)
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 = 1,463 (80% power), 1,959 (90% power)
 75% of observed effect: n per arm = 2,601 (80% power), 3,481 (90% power)
 50% of observed effect: n per arm = 5,851 (80% power), 7,833 (90% power)
power.t.test: 1463.6 
Simulated power at n = 1,463 per arm: 0.804 (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 a Wilcoxon Rank Sum Test for superiority, with a reported p-value of 0.750. The recalculation uses the posted group means and standard deviations to estimate an unadjusted mean difference of 2.1 grams, with an interval from -7.848 to 12.05 grams and an unadjusted p-value of 0.679.

These analyses use different statistical approaches. The Wilcoxon test is rank-based, whereas the recalculation compares arithmetic means. A p-value from one method is not expected to equal a p-value from another, and the mean-difference interval is not an interval for the Wilcoxon test. The registry does not report an effect estimate or confidence interval for its rank-based analysis, so the mean-based recalculation adds an interpretable contrast from the posted summaries but does not reproduce the sponsor’s full analysis.

The discrepancy flag is false. The recalculation should therefore be read as a complementary, unadjusted analysis of aggregate results rather than as evidence that the registry’s analysis is inconsistent with the posted data. The registry’s reported analysis remains the study’s own inferential result; details of its analysis plan, including prespecification and any other planned analyses, are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes. When several outcomes are tested, the chance of at least one apparently positive result can increase if each is evaluated without accounting for the others. A multiplicity approach can define how evidence is interpreted across outcomes, for example by controlling the overall error rate or by specifying a hierarchy of tests. The registry record does not report whether such an approach was planned, which outcomes were included in any adjustment, or whether secondary analyses were considered confirmatory or exploratory.

The recalculated p-values are unadjusted. They do not account for the number of outcomes or analyses. The registry’s reported Wilcoxon p-value is the stated primary analysis, but the record does not provide the full statistical analysis plan or enough information to determine whether other testing decisions were prespecified. The secondary results should not be treated as if multiplicity had been addressed.

The primary endpoint population is described as all enrolled participants who underwent successful PPCI and CMR without major protocol deviations, labelled the per-protocol population. Its group counts are 28 and 36. The enrollment figure is 78, but the registry record does not explain why participants were not included in the endpoint population, report participant flow by reason, or describe how missing CMR measurements were handled. It also does not report an intention-to-treat primary analysis or a sensitivity analysis for missing outcomes.

Missing data can affect both the precision and interpretation of a comparison, particularly if the likelihood of having an outcome measured differs by treatment group or is related to the outcome itself. The registry’s aggregate results do not show whether that occurred. No assumptions about the missingness mechanism, imputation method, or robustness analysis are reported in the registry record.

The sample-size illustration uses assumptions stated for planning, but the original trial’s sample-size justification, analysis populations beyond the primary population description, interim analyses, and detailed statistical plan are not reported in the registry record. The terminated status does not explain whether a planned analysis was altered or whether data collection stopped for a particular reason. Those omissions limit assessment of selective reporting and the intended inferential framework.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiogenic shock (5.3%), cardiac arrest (5.0%), cardiac tamponade (2.6%), coronary artery perforation (2.6%), myocardial rupture (2.6%).

The registry reports serious adverse events for 6 of 38 participants at risk in the bivalirudin group and 7 of 40 in the heparin group. Other adverse events are reported for 11 of 38 and 6 of 40, respectively. Deaths are recorded as 1 in each group. These are descriptive counts with the reported at-risk denominators; they are not a randomized comparison adjusted for follow-up time or other factors.

The registry also lists serious adverse event terms with percentages: cardiogenic shock, 5.3%; cardiac arrest, 5.0%; cardiac tamponade, 2.6%; coronary artery perforation, 2.6%; myocardial rupture, 2.6%; and ventricular fibrillation, 2.6%. The record does not provide, alongside this list, enough detail to infer the number of participants affected by each term or whether a participant could have more than one event. These percentages should be read as registry-listed values, not converted into counts.

The adverse-event summaries do not establish that one treatment is safer than the other. The record does not provide event timing, duration of observation for each participant, severity details beyond the serious-event classification, or a statistical comparison. Differences in counts can reflect variation as well as treatment, and the available summaries do not support causal conclusions. The safety figures should be considered alongside the trial’s limited enrollment and terminated status, without inferring a reason for termination.

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

The primary result describes the observed Day 5 CMR infarct-size means in the per-protocol population and the uncertainty around their unadjusted mean contrast. The mean was 25.0 grams in the bivalirudin arm and 27.1 grams in the heparin arm. The recalculated contrast is 2.1 grams for heparin minus bivalirudin, with an interval that includes zero and extends across values in both directions. The registry’s own rank-based test also does not report a statistically clear separation between groups.

These results do not establish that the treatments have the same effect. A result that does not show a clear difference is not a demonstration of equivalence. The interval is broad, and the registry does not report an equivalence margin or a non-inferiority design. Nor do the results establish that either treatment reduces heart-muscle damage: the posted comparison is an estimate from a specific study population, outcome measure, and time point.

The primary endpoint is an imaging measure at Day 5, not a direct measure of how participants feel, function over time, or experience later clinical events. The registry lists additional outcomes, but numerical results are available for only some of the secondary measures. Those secondary results do not form a uniformly directional pattern and should not be used to claim a broader treatment effect.

The observed data also do not show what would happen in every participant or in other populations. The primary analysis excludes participants who did not meet the stated per-protocol conditions. The record does not report how missing measurements were handled or provide a full account of participant flow. These limits matter when applying the result beyond the analyzed group.

In short, the posted results leave uncertainty about the size and direction of the mean infarct-size difference. They neither prove a meaningful benefit nor rule one out. The clinical importance of any possible difference cannot be judged from statistical results alone, and a threshold for clinical importance is not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates the distinction between an observed difference and a precise estimate of that difference. The primary group means are separated by 2.1 grams in the mean-based recalculation, but the interval extends from -7.848 to 12.05 grams. A point estimate alone can appear concrete; its uncertainty shows why a small study’s result should not be interpreted as a definitive ranking of treatments.

It also illustrates why the analysis method matters. The registry reports a Wilcoxon Rank Sum Test, while a recalculation from the posted summary statistics compares means. Both can be legitimate statistical summaries for different questions, but their estimates and p-values are not interchangeable. The registry does not publish the full inferential output for its rank-based analysis, so the aggregate mean-based calculation cannot fill every gap in the sponsor’s analysis.

The endpoint population is another important statistical feature. The primary analysis is per protocol and includes participants with successful PPCI and CMR without major protocol deviations. The enrollment figure and the endpoint-specific counts are not the same, and the registry does not give a full explanation of the difference. This makes participant flow and missing-outcome handling relevant to interpretation rather than administrative details.

Finally, the record provides an example of the limits of secondary-outcome interpretation. Some numerical results are posted, other listed outcomes lack numerical results, and multiplicity handling is not reported. A collection of secondary comparisons cannot be treated as a single confirmatory test without knowing how they were planned and interpreted. Together, these features show why estimates, uncertainty, population definitions, and reporting completeness must be read alongside p-values.

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 primary endpoint is reported for a per-protocol population rather than all enrolled participants. The registry defines that population by successful PPCI and CMR without major protocol deviations, but does not provide participant flow or explain exclusions from the endpoint analysis. This limits assessment of whether the analyzed participants remain comparable under the randomized assignment and whether missing endpoint measurements could affect the result.

The primary results are aggregate means, standard deviations, and group counts. Participant-level data and distributional summaries are not reported, so the recalculation cannot assess influential observations, skewness, or other features that could matter when comparing means. The sponsor’s reported Wilcoxon analysis lacks a reported effect estimate and confidence interval, which limits direct evaluation of the size and precision under that method.

The record does not report the original sample-size justification, interim-analysis plan, or full statistical analysis plan. It also does not report a clinical-importance threshold for infarct size, or a multiplicity strategy for the several secondary outcomes. The planning illustration is based on the observed effect and cannot be used to establish what the original trial was designed to detect.

Only some secondary outcomes have numerical results in the registry record. The listed outcomes without numerical results cannot contribute to a complete account of the trial’s secondary findings. The reported adverse-event summaries are descriptive and do not provide a detailed account of event timing, follow-up duration, or a statistical safety comparison.

The study status is terminated, but the reason for termination is not reported in the registry record. It is therefore not possible to infer whether termination related to recruitment, safety, efficacy, logistics, or another cause. These reporting limits, the modest endpoint counts, and the broad primary interval warrant caution in interpreting the results beyond the stated study population and measurements.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Bivalirudin Infusion for Ventricular Infarction Limitation — NCT02565147.
• Registry record last updated 2018-10-05; status last verified 2017-12.
• Results first posted 2018-10-05.
• 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

The registry record describes a randomized, single-masked, parallel Phase 3 trial of PPCI with bivalirudin versus PPCI with heparin in acute myocardial infarction. Enrollment is 78, and the study status is terminated. The primary outcome is CMR-assessed infarct size in grams at Day 5 among participants who underwent successful PPCI and CMR without major protocol deviations.

The posted primary group means are 25.0 grams for bivalirudin and 27.1 grams for heparin. The registry reports a Wilcoxon Rank Sum Test for superiority; a separate unadjusted mean-based recalculation gives a difference of 2.1 grams, with an interval from -7.848 to 12.05 grams. The interval is broad and includes zero. Numerical secondary results are available for three continuous measures, while results for other listed secondary outcomes are not reported in the registry record.

The record does not report the original sample-size justification, multiplicity plan, or reason for termination. The findings should be interpreted as uncertain estimates for the stated per-protocol population, not as proof of benefit, harm, or equivalence.