A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (NCT03578809), a randomized phase 2 study. The primary outcome is Global Infarct Size.

2. Clinical Question

The record describes a randomized, placebo-controlled study of MEDI6012 in acute STEMI. Its primary outcome is a measurement of myocardial injury at follow-up, rather than an outcome such as survival or symptoms. The listed primary endpoint is reported separately for the two cohorts and their assigned treatment groups. The registry record does not give a posted two-arm inferential comparison for this endpoint, so the group estimates should be read as descriptive summaries, not as a formal estimate of a treatment effect.

3. Trial Design

This was a randomized, placebo-controlled Phase 2b study with triple masking and a parallel-group model. The registry record lists enrollment of 593 and status as completed. The listed study start date is 2018-06-05 and the primary completion date is 2021-01-18. Participants were adults presenting with acute STEMI who were planned for primary percutaneous coronary intervention.

The study used two dosing cohorts. In Cohort A, participants assigned to MEDI6012 received a 300 mg loading dose on Day 1 before primary percutaneous coronary intervention, followed by 150 mg on Day 3. Cohort A placebo participants received matched placebo on those days. In Cohort B, the same Day 1 and Day 3 pattern was followed by outpatient maintenance dosing on Days 10, 17, 24, and 31: 100 mg MEDI6012 or matched placebo. The posted results do not provide a separate account of the reason for the two cohort schedules.

All participants were scheduled for an end-of-study cardiovascular magnetic resonance scan at 10-12 weeks, described as 70-84 days after Dose 1. A subset was also to undergo computed tomography angiography at the index assessment and at end of study. The primary efficacy population was narrower than the broad trial population: it comprised randomized participants with TIMI flow Grade 0-1 on initial angiography who received at least 2 doses, grouped according to assigned treatment. The registry record does not report a sample-size justification or explain how the analysis population was defined beyond that description.

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: In total, 593 participants were randomized into the study and 575 participants were treated with the study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary efficacy analysis population included randomized participants with a Thrombolysis in Myocardial Infarction (TIMI) flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure.

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: Intent-to-treat (ITT) population included all randomized participants, grouped according to assigned treatment.

6. Primary Endpoint

The registry lists the primary outcome as Global Infarct Size, measured over 70 to 84 days post Day 1 dose.

The primary endpoint is global infarct size, expressed as a percentage of left ventricular mass. It was assessed using delayed-enhanced cardiovascular magnetic resonance imaging 70 to 84 days after the Day 1 dose, at the planned 10-12-week end-of-study assessment. The registry record reports the endpoint as a geometric mean with a 90% confidence interval for each listed group.

In general, infarct size is a measure of the amount of heart muscle affected by the myocardial infarction. Expressing it relative to left ventricular mass provides a scale related to the size of the ventricle, while magnetic resonance imaging provides the imaging-based assessment specified in the protocol summary. This outcome captures structural injury at a defined follow-up period; it is not itself a direct measure of symptoms, subsequent clinical events, or survival.

The timing matters to interpretation: the reported measure concerns imaging at follow-up, not an immediate post-procedure assessment. The registry record describes the endpoint and its measurement, but the posted primary results do not include a treatment-effect estimate, confidence interval for a between-group contrast, or reported inferential test. Consequently, group-level estimates can describe the observed measurements, but they do not by themselves establish whether assignment to MEDI6012 changed infarct size relative to placebo.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical results are easiest to interpret when the measurement, summary statistic, comparison, and population are kept distinct. The primary endpoint is a continuous imaging measure: global infarct size as a percentage of left ventricular mass. The registry record summarizes it with geometric means and 90% confidence intervals. The secondary ventricular-mass outcomes instead use arithmetic means and standard deviations. These summaries answer different descriptive questions, so they should not be treated as interchangeable.

What does a geometric mean describe?

In general, a geometric mean is calculated on a multiplicative rather than additive scale. It is often useful for positive measurements whose distribution is skewed, because large observations have less influence than they would on an arithmetic mean. The posted primary outcome is identified as a geometric mean, but the registry record does not report the distributional assessment or analysis rationale behind that choice. The reported group values describe central tendency on the scale used by the registry; they are not a direct between-group effect estimate.

How should the confidence intervals be read?

In general, a confidence interval conveys the precision of an estimate under a particular statistical method and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale. A group-specific interval concerns that group's estimated value. To assess a treatment contrast, an analysis should estimate the difference or other relevant effect directly and provide uncertainty around that contrast. Comparing two separate group intervals informally is not equivalent to testing the treatment effect. For the primary endpoint, the registry record posts 90% confidence intervals for each group but no confidence interval for a between-group contrast.

The primary endpoint's intervals therefore allow readers to see the uncertainty around the group summaries, but they cannot supply the missing contrast. The posted values are also tied to a defined analysis population: randomized participants with TIMI flow Grade 0-1 on initial angiography who received at least 2 doses, classified according to assigned treatment. This population is not automatically interchangeable with all participants enrolled in the trial.

What do the secondary comparisons add?

For the two posted left ventricular mass outcomes, the registry lists group means and standard deviations. Unadjusted re-calculations use those summary statistics to estimate mean differences for selected comparisons. For late gadolinium enhancement, the MEDI6012-versus-Cohort A placebo re-calculation is a mean difference of -0.159 g with a 95% confidence interval from -10.68 to 10.36 and p = 0.976. The Cohort B placebo comparison is -4.519 g, with a 95% confidence interval from -16.29 to 7.251 and p = 0.452. For cine magnetic resonance imaging, the corresponding Cohort A comparison is -0.083 g, with a 95% confidence interval from -10.54 to 10.38 and p = 0.988; the Cohort B placebo comparison is -3.709 g, with a 95% confidence interval from -15.4 to 7.983 and p = 0.534.

These are simple, unadjusted re-calculations from posted summary statistics, not analyses reported by the registry. In general, an unadjusted comparison does not account for other covariates, stratification, or multiplicity unless those are explicitly incorporated. The registry record does not provide reported analyses for these outcomes, and it does not state whether these simple contrasts match the study's planned analysis. The confidence intervals are broad relative to the point estimates, so the re-calculations leave considerable uncertainty about the direction and size of the mean differences.

What do the planning illustrations mean?

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen probability, called power. The planning illustrations associated with the recalculations are based on the observed effect and assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. Other rows use stated fractions of the observed effect. These are planning illustrations, not observed power, and they are not the design justification for this trial. The registry record does not report the trial's own sample-size assumptions or justification. An observed result cannot be converted into a retrospective statement about whether the trial had adequate power without a prespecified target effect and appropriate design information.

Why does the analysis population matter?

Randomization establishes the original assigned groups, but a reported analysis may include a narrower set of participants. The primary efficacy population excludes participants who did not meet the stated initial angiography criterion or receive at least 2 doses. The record says participants were grouped according to assigned treatment, but does not provide a fuller account of missing imaging data, exclusions, or the handling of participants without an endpoint measurement. In general, exclusions after randomization can affect how well the comparison retains the benefits of random assignment. Without detailed accounting, it is difficult to assess the potential effect of those exclusions.

Finally, a p-value measures how surprising data at least as extreme as those observed would be under a specified null model and assumptions. It is not the probability that the null hypothesis is true, nor does it measure clinical importance. The secondary p-values are unadjusted recalculations and should not be treated as confirmatory findings. The primary endpoint has no posted p-value or treatment contrast in the registry record, so it cannot be assigned an inferential interpretation from the group summaries alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was addressed. Multiplicity arises when a study evaluates several outcomes, time points, or treatment comparisons: even if each statistical test uses a conventional threshold, the chance of at least one apparently notable result can increase as the number of tests grows. In general, a prespecified hierarchy, adjustment procedure, or clearly defined exploratory framework helps readers distinguish confirmatory evidence from results intended to generate hypotheses. No such strategy is described in the registry record, so the unadjusted secondary p-values should not be interpreted as confirmatory evidence.

The record specifies a primary efficacy analysis population: randomized participants with TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug, grouped according to assigned treatment. It does not report a fuller analysis-population plan, the number screened or excluded for each criterion, or the reasons participants may not have contributed an imaging result. The enrollment figure of 593 should not be confused with the number analyzed for the primary outcome. The primary group-level results show analysis counts for the four groups, but the registry description does not explain the full path from enrollment to endpoint analysis.

Missing-data handling is not reported in the registry record. In general, missing outcomes can reduce precision, and the reasons for missingness can affect interpretation if the probability of missing a measurement is related to participant characteristics or outcomes. The record does not say whether missing imaging values were imputed, whether sensitivity analyses were conducted, or how participants without a scan were treated in the analysis. The summary description also does not report interim analyses, a detailed statistical analysis plan, or the trial's sample-size justification. These absences do not prove that such procedures were not conducted; they mean the registry record does not document them. Without these details, the extent to which the posted summaries represent the randomized population and planned analyses cannot be fully assessed.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure (2.8%), acute myocardial infarction (2.2%), angina unstable (1.8%), atrial fibrillation (1.8%), cardiac failure acute (1.8%).

The posted serious adverse event figures are counts of affected participants and the corresponding numbers at risk, reported separately for placebo and MEDI6012 in Cohorts A and B. The figures should be read within each cohort and treatment group, rather than combined into an overall comparison. The record lists 11 of 90 for placebo in Cohort A and 34 of 179 for MEDI6012 in Cohort A; for Cohort B it lists 24 of 111 for placebo and 41 of 195 for MEDI6012. Deaths are listed as 0, 2, 0, and 1 for those groups, respectively.

These counts are descriptive. The registry record does not provide a statistical comparison of serious adverse events, a time-to-event analysis, or adjusted estimates. Serious events can differ in type and clinical context, and counts alone do not indicate whether an event was caused by study treatment. The listed common serious-event terms include cardiac failure, acute myocardial infarction, unstable angina, atrial fibrillation, acute cardiac failure, and Dressler's syndrome, with percentages reported in the registry record. These terms provide context for the event listings but do not establish comparative risk. The counts should be interpreted alongside the study's population, follow-up, and absence of a reported safety analysis, rather than as proof of a causal safety difference.

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

The posted results describe outcomes observed among participants included in the registry analyses. They report group-level primary endpoint estimates and a selection of secondary outcome summaries, as well as adverse-event counts. The results provide a record of what was measured and the values posted for those groups. They do not provide a reported treatment-effect estimate for the primary endpoint.

For the primary outcome, a group mean and its confidence interval answer a descriptive question about that group. They do not show how the outcome would differ under MEDI6012 versus placebo for comparable participants. A direct comparison requires an estimated contrast and uncertainty around that contrast. Because that primary comparison is not reported in the registry record, neither the direction nor the precision of a primary treatment effect can be established from the group summaries alone.

The secondary re-calculations are also limited. They are unadjusted calculations from posted summary statistics, not registry-reported inferential analyses. Their p-values do not establish that a treatment effect is absent or present, and the confidence intervals indicate substantial uncertainty. The absence of a statistically notable result is not proof of equivalence; a claim of equivalence or non-inferiority would require a relevant prespecified margin and analysis, neither of which is reported in the registry record.

Likewise, adverse-event counts can describe what was recorded but cannot, without an appropriate comparative analysis and context, identify the cause of events or establish a treatment-related difference. The registry record does not report a statistical safety comparison.

These limitations do not make the posted measurements uninformative. They define what can responsibly be concluded: the record documents a randomized study, its outcome measures, and group-level results, while leaving important inferential details unavailable. Stronger conclusions about efficacy, safety, or consistency across outcomes would require a reported analysis plan, treatment-effect estimates, uncertainty measures for the primary contrast, and fuller accounting of the analyzed populations and missing data. The results should therefore be read as descriptive evidence rather than as a definitive answer about the effect of MEDI6012.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a randomized, placebo-controlled design with an imaging-based primary outcome and two dosing cohorts. Randomization is intended to support a fair comparison of assigned treatments, while masking can reduce the influence of expectations on trial conduct and outcome assessment. The registry record identifies the study as triple masked, but does not specify which roles were masked or describe implementation details. The parallel-group design compares participants assigned to ongoing groups rather than relying on a within-person treatment crossover.

The primary endpoint is a quantitative imaging measure collected at follow-up. That gives the trial a structural outcome tied to myocardial injury, but the endpoint's group summaries do not by themselves answer the comparative question. The lack of a posted primary contrast illustrates a practical distinction in registry interpretation: a measure can be reported without the inferential analysis needed to evaluate treatment differences. Reporting both an effect estimate and its uncertainty is central to understanding what a randomized comparison says.

The two dosing schedules also make the cohort context important. Cohort B includes outpatient maintenance doses beyond the shared initial dosing pattern, so its summaries should not be casually combined with Cohort A or treated as though every participant received an identical regimen. The record does not explain the reason for the cohort structure, and no pooled treatment estimate is posted.

Finally, the trial demonstrates why secondary results, safety counts, and missing-data details must be read together. A range of measurements can enrich the clinical picture, but multiple outcomes invite multiplicity concerns, and incomplete reporting can obstruct assessment of the analysis population. Statistical interpretation depends not only on reported values but also on the comparison, uncertainty, population, and analysis plan attached to them.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting efficacy is that the registry record reports the primary outcome by group but does not post a between-group effect estimate or inferential test. The displayed geometric means and confidence intervals cannot replace a direct analysis of MEDI6012 versus placebo. This leaves the principal comparative question unresolved in the posted results.

The primary analysis population is restricted to randomized participants with TIMI flow Grade 0-1 on initial angiography who received at least 2 doses. The registry record does not provide a full accounting of exclusions, endpoint availability, or the reasons participants may not have contributed imaging measurements. Because the number enrolled is not the same as the number included in each endpoint analysis, the relationship between the enrolled and analyzed populations is not completely described.

The summary states that all participants were to have end-of-study CMR and that a subset would undergo CTA, but does not report detailed completion or missing-data information. It also does not report the statistical methods used for the primary endpoint beyond the stated summary measure, or describe adjustments, sensitivity analyses, or the handling of missing values. These omissions limit assessment of precision and robustness.

There are also limits to the secondary evidence. Only selected secondary results have numerical summaries and recalculated comparisons; the registry record lists other outcomes without providing a complete set of numerical results or reported analyses. The recalculated comparisons are unadjusted and should not be treated as the trial's own prespecified analyses. Multiplicity handling is not reported. Finally, the registry record does not explain the rationale for the cohorts or give the trial's sample-size justification, limiting assessment of how the design was intended to address a target effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction — NCT03578809.
• Registry record last updated 2022-02-09; status last verified 2022-01.
• Results first posted 2022-02-09.
• 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.

18. Record Summary

The registry record describes a completed, randomized, triple-masked, placebo-controlled Phase 2b parallel-group study of MEDI6012 in adults presenting with acute STEMI who were planned for primary percutaneous coronary intervention. It lists enrollment of 593 and an end-of-study imaging assessment 70 to 84 days after the Day 1 dose. Participants were assigned to Cohort A or Cohort B schedules, with Cohort B including outpatient maintenance doses.

The primary endpoint was global infarct size as a percentage of left ventricular mass measured by delayed-enhanced CMR. Results are posted as geometric means and 90% confidence intervals for four treatment-cohort groups. The registry record does not report a primary between-group comparison. Selected ventricular-mass secondary outcomes have group summaries and unadjusted recalculations, while the record lists additional outcomes without a complete set of reported analyses. Serious adverse-event counts are presented by group without a reported comparative safety analysis.