Study to Evaluate the Effect on Parameters of Systemic Inflammation and Disease Outcomes and Safety of RPH-104 in Subjects With Acute ST-elevation Myocardial Infarction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Effect on Parameters of Systemic Inflammation and Disease Outcomes and Safety of RPH-104 in Subjects With Acute ST-elevation Myocardial Infarction (NCT04463251), a randomized phase 2 study. The primary outcome is High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure).

2. Clinical Question

3. Trial Design

This was an international, randomized, double-blind, parallel-group, placebo-controlled phase 2 study in subjects with acute STEMI. The registry records an enrollment of 102 and a completed status. The study start date is 2020-12-07, and the primary completion date is 2021-11-03. Further details about participating countries, the randomization procedure, allocation concealment, or the planned allocation ratio are not reported in the registry record.

The three described groups were RPH-104 80 mg, RPH-104 160 mg, and placebo. The 80 mg group received a single 2 mL injection of RPH-104 and a 2 mL placebo injection at different sites. The 160 mg group received two 2 mL injections of RPH-104, each described as 80 mg, at different sites. The placebo group received two 2 mL placebo injections at different sites. The registry lists RPH-104 80 mg and placebo in its intervention list, while its arm descriptions also include the RPH-104 160 mg group.

The primary outcome was hsCRP AUC from baseline through Day 14, analyzed using multiple imputation. Group summaries are geometric least squares means with 95% confidence intervals. The primary efficacy population is described as randomized subjects who received study product and had at least one hsCRP measurement after administration. Some of the population description is incomplete, so further details are not reported in the registry record.

The registry lists secondary measures spanning hsCRP, fatal outcomes, hospitalizations, heart failure, BNP, and end-diastolic volume. Some outcomes are followed through 12 months. The record does not describe the rationale for the selected enrollment, the randomization details, or an interim analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set for efficacy analysis included all randomized subjects who received the study products (RPH-104 or placebo), and underwent at least one hsCRP measurement after administration of the study products. The FAS was the main population for efficacy assessment. Multiple imputation procedure was performed for hsCRP values which were missed on Day 14.

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 High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure), measured over Day 1 until Day 14.

The primary endpoint is hsCRP area under the curve from baseline, identified as Day 1, until Day 14. AUC combines measurements across a specified interval into a measure of accumulated exposure; it is not simply a single measurement at the end of follow-up. In this study, the endpoint is intended to summarize the pattern of hsCRP measurements over the early post-administration period. hsCRP is used in the study as a parameter of systemic inflammation, consistent with the stated study objective.

The registry reports geometric least squares mean summaries, with a 95% confidence interval for each group. A geometric summary is suited to data analyzed on a multiplicative scale; the registry’s reported between-group estimates are ratios of least squares means. A ratio gives a relative comparison, while each group’s AUC summary describes the estimated level on the endpoint’s stated scale, mg*day/L. The confidence interval communicates uncertainty around the estimated group summary or ratio under the analysis used.

The primary endpoint uses a multiple imputation procedure. Imputation is a way to address missing measurements by incorporating estimates for missing values into the analysis rather than restricting the analysis to observed complete records alone. The specific imputation model and its assumptions are not reported in the registry record. The registry also lists hsCRP AUC analyses using multiple imputation and complete cases among the secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary estimate represent?

The primary outcome is a continuous measure: hsCRP AUC from baseline through Day 14, in mg*day/L. AUC captures the accumulated values over a stated interval, allowing measurements made at different times within that period to contribute to one summary. The registry reports geometric least squares means rather than arithmetic means. In general, a geometric summary reflects analysis on a multiplicative scale, which can be useful when the outcome is analyzed through transformations or when relative comparisons are of interest. The registry does not provide the full model specification or transformation details.

The reported comparisons are least squares means ratios. In general, a ratio compares estimated levels on a relative scale: a ratio of 1 represents equal estimated levels, and values below or above 1 indicate lower or higher estimated levels in the numerator group relative to the reference group. For this primary endpoint, the record reports a ratio of 0.58 for each active-group comparison with placebo. This interpretation is about the estimated AUC, not the probability of an individual outcome or the size of a clinical benefit.

How should confidence intervals be read?

A confidence interval expresses uncertainty around an estimate under the statistical procedure used. A narrower interval indicates greater precision than a wider interval, all else being equal. The primary group summaries and ratios are accompanied by 95% confidence intervals. Those intervals should not be read as containing 95% of individual participants’ measurements. They also do not account for design or analysis problems that are not represented in the model.

For a ratio, the value 1 is the no-difference reference. The reported primary ratio intervals are below that reference, which is consistent with lower estimated hsCRP AUC in each active group than in placebo under the reported analysis. That observation does not establish the clinical importance of the difference. A p-value is not reported for the primary comparisons, and a p-value would not convey the magnitude or precision of an effect by itself.

Why use multiple imputation?

The primary endpoint uses multiple imputation. In general, this approach uses a statistical model to generate plausible values for missing observations, analyzes completed versions of the data, and combines the resulting estimates so that uncertainty due to missingness can be reflected. It can retain information from participants who do not have every planned measurement, unlike a complete-case analysis that uses only records with all required measurements.

Multiple imputation depends on assumptions about the relationship between observed and missing data and on the model used to create the imputations. The registry record does not report the specific imputation model, the number of imputations, the missing-data pattern, or the assumptions used. Therefore, the robustness of the primary result to alternative missing-data assumptions cannot be assessed from the record alone. The registry also lists a complete-case hsCRP AUC analysis as a secondary outcome, but the detailed result is not included in the registry record for this explanation.

What can rare binary outcomes tell us?

The posted secondary comparisons include binary outcomes recorded as participant counts. For a binary endpoint, a risk difference expresses the difference between the estimated event proportions in two groups on the absolute scale. Its confidence interval indicates uncertainty in that difference. When event counts are sparse, estimates can be unstable and confidence intervals may be wide. In general, a lack of statistical evidence for a difference in such data is not evidence that the groups are equivalent.

The registry’s secondary comparisons include unadjusted p-values and, for one comparison, a confidence interval for a risk difference that spans values on either side of no difference. These results are exploratory descriptions, not a substitute for a prespecified and adequately precise test of a clinical outcome. No adjusted secondary analyses are listed in the record.

How should sample-size illustrations be interpreted?

The sample-size illustrations use the observed effect and are not the trial’s design justification. They give participants per arm for 80% power and participants per arm for 90% power under the stated planning assumptions: a two-sided significance level of 0.05, equal allocation, a normal approximation, and detection of a stated fraction of the observed effect. These are planning illustrations, not observed power and not a statement about the probability that the trial detected an effect. A design rationale or sample-size justification is not reported in the registry record.

For an outcome with very few observed events and an estimate near no difference, planning calculations based on the observed effect can imply very large sample requirements. That reflects the small estimated contrast used in the calculation and its uncertainty; it does not mean that a future study must use exactly those sizes. Planning at a fraction of the observed effect also asks about a different target effect from planning at the full observed estimate. The illustration should therefore be treated as a sensitivity exercise around an observed estimate, not as a forecast or a reconstruction of the study’s original design.

10. Analyses Reported by the Sponsor

The registry reports the primary analysis as a least squares means ratio of 0.58 for RPH-104 80 mg versus placebo, with a 95% confidence interval of 0.37 to 0.91, and a ratio of 0.58 for RPH-104 160 mg versus placebo, with the same interval. These are the reported analyses for the primary endpoint. The registry does not give a p-value or further details of the analysis method, and a separately recalculated primary comparison is not reported in the registry record.

Accordingly, interpretation of the primary endpoint rests on the registry’s reported estimates and intervals. There is no recorded conflict between a sponsor-reported primary result and a recalculation in the registry record for this analysis. The result should not be supplemented with an independently calculated estimate that is not reported.

For the posted secondary binary comparisons, unadjusted recalculations are available, but the registry does not list corresponding reported analyses. Those recalculations are simple comparisons based on the posted group summaries and should be distinguished from an analysis reported by the study sponsor. They are not a replacement for a prespecified analysis plan or for sponsor analyses that are not reported in the registry record. The primary result and the secondary recalculations therefore have different evidential status: the former is the registry’s reported analysis, while the latter are unadjusted re-calculations of posted summary data.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies hsCRP AUC through Day 14 as the primary endpoint and lists multiple secondary outcomes. It records 28 outcome measures, 12 analyses, and 24 secondary outcomes as posted. Examining numerous outcomes can increase the chance of observing a result that appears notable by chance. Statistical procedures that control this multiplicity, or a prespecified strategy that prioritizes outcomes, can help clarify which comparisons are confirmatory. Such procedures or a hierarchy are not reported in the registry record.

The primary analysis uses multiple imputation. That identifies a method for addressing missing measurements, but the description of the procedure is incomplete. The imputation model, assumptions about missingness, number of imputations, and sensitivity analyses are not reported in the registry record. The complete-case hsCRP AUC measure is listed as a secondary outcome, but its detailed estimate and the relationship between that analysis and the primary result are not reported in the registry record.

The primary population is described as a full analysis set for efficacy assessment, including randomized subjects who received study product and had at least one hsCRP measurement after administration. The remainder of the population description is incomplete, so additional inclusion or exclusion details are not reported in the registry record. The record does not provide the analysis population definitions for every secondary outcome.

The allocation, masking, and parallel design are described, but additional information about the statistical analysis plan, handling of protocol deviations, interim analyses, and sensitivity analyses is not reported in the registry record. These omissions limit assessment of whether the reported analyses followed a prespecified plan and how robust the estimates are to alternative analytic choices. The registry’s stated enrollment does not supply a sample-size rationale; the rationale and assumptions behind the original design are not reported in the registry record.

12. 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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (5.9%), atrial fibrillation (2.9%), atrioventricular block complete (2.9%), gastric disorder (2.9%), gastric haemorrhage (2.9%).

The registry reports serious adverse events for the treatment groups as counts among participants at risk: 7 in the RPH-104 80 mg group, 1 in the RPH-104 160 mg group, and 4 in the placebo group. It reports other adverse events as 21, 20, and 14, respectively. Death counts are 1, 0, and 1, respectively. These figures describe the posted safety record and should not be interpreted as adjusted comparisons between groups.

The registry also lists pre-treatment monitoring groups separately. Serious adverse events were recorded as 0 in each of those groups; other adverse events were 3, 3, and 2. The listed serious-event terms include unstable angina at 5.9%, atrial fibrillation at 2.9%, complete atrioventricular block at 2.9%, gastric disorder at 2.9%, gastric haemorrhage at 2.9%, and cardiac death at 2.9%. The record does not provide an arm attribution for those term percentages in the registry record for this explanation.

Safety counts alone do not establish that an event was caused by treatment or that groups differ reliably. The registry does not report detailed event-level timing, severity beyond the serious-event classification, or statistical comparisons for these figures. The at-risk count for the placebo safety group is 34, while the primary efficacy summary reports 33 for placebo; the different reported denominators should be kept distinct rather than combined.

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

The primary result is an estimate of hsCRP AUC from Day 1 through Day 14. The reported geometric least squares mean values are lower in both RPH-104 groups than in placebo, and both reported ratios versus placebo are 0.58 with 95% confidence intervals of 0.37 to 0.91. This is evidence about the endpoint and analysis reported in the registry, not a direct estimate of later clinical outcomes.

The result does not establish whether RPH-104 changes the risk of death, hospitalization, or heart failure. Those outcomes are distinct from hsCRP AUC, and the posted secondary events are sparse. Nor does the primary comparison show whether 80 mg and 160 mg differ from one another: a direct active-dose comparison is not reported in the registry record. The matching point estimates against placebo do not prove the doses are equivalent.

The confidence intervals communicate uncertainty but do not capture every possible source of uncertainty, including limitations from missing-data assumptions or unreported model details. The multiple imputation procedure is named, but its specifics are not reported in the registry record. The reported primary result should therefore be understood as conditional on the analysis used, with the available description limiting independent assessment of its robustness.

The registry describes this as a phase 2 study with an enrollment of 102. It does not report a sample-size justification, full statistical analysis plan, or multiplicity strategy. These omissions matter when interpreting precision and the number of outcomes examined. The findings are best described narrowly: the posted primary analysis estimates lower early hsCRP exposure in each RPH-104 group relative to placebo, while the size, precision, and implications of that difference require cautious interpretation. No treatment recommendation follows from these registry results alone.

14. Why This Trial Matters Statistically

This trial is statistically informative because it separates an early biological measure from longer-term clinical outcomes. The primary endpoint summarizes hsCRP over Day 1 through Day 14, while the secondary outcome list includes measures extending to 12-month follow-up. Keeping those questions distinct prevents an inflammation estimate from being mistaken for evidence about later events.

The registry also illustrates why effect estimates and uncertainty should be read together. The primary ratios are below 1 and their reported confidence intervals are below 1, but the intervals still allow a range of relative effects. The group summaries themselves also have confidence intervals. Reporting the estimates with their uncertainty gives more information than a binary claim based only on whether a threshold was crossed.

A further statistical issue is the distinction between a reported primary analysis and exploratory secondary comparisons. Multiple outcomes can produce chance findings, and no multiplicity strategy is reported. Sparse event counts also limit the precision of secondary comparisons. Those features make it important not to use isolated secondary results as though they independently confirmed the primary endpoint.

Finally, the missing detail on imputation, analysis populations, and design justification matters for reproducibility. The record names multiple imputation and describes the primary efficacy population in part, but does not give the full assumptions or model. This means readers can interpret the stated estimate and its reported interval, while recognizing that a fuller assessment of analytic robustness is not possible from the registry record alone.

15. 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 covers Day 1 through Day 14, so it addresses early hsCRP exposure rather than the full range of disease outcomes. Although longer-term outcomes are listed, detailed results are not reported for every outcome in the registry record. The clinical event comparisons that are posted have very few observed events, which limits precision and makes estimates sensitive to small changes in counts.

The study enrollment is 102, and the primary group summaries report 34 participants in each RPH-104 group and 33 in placebo. The safety record reports 34 at risk in the placebo group. These are endpoint-specific reported values and should not be silently reconciled or combined. Reasons for the differing denominators are not reported in the registry record.

The primary endpoint’s multiple imputation procedure is named, but its model, missingness assumptions, and sensitivity analyses are not reported. The full analysis population description is also incomplete. Further statistical details, including the original sample-size justification, multiplicity plan, and interim analysis information, are not reported in the registry record. These gaps restrict assessment of whether the findings are robust to analytic choices and how the study was designed to address its stated questions.

The record reports no direct comparison between the two active doses. It also does not provide detailed sponsor analyses for the secondary outcomes. The secondary outcome roster is broad, but the absence of a reported multiplicity strategy and complete results means that the overall secondary evidence cannot be evaluated as a single confirmatory analysis. Safety figures are descriptive counts, and detailed event attribution and comparative analyses are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Effect on Parameters of Systemic Inflammation and Disease Outcomes and Safety of RPH-104 in Subjects With Acute ST-elevation Myocardial Infarction — NCT04463251.
• Registry record last updated 2024-06-24; status last verified 2024-05.
• Results first posted 2024-01-24.
• 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.

19. Record Summary

The registry describes a completed, international, randomized, double-blind, parallel, placebo-controlled phase 2 study of RPH-104 in subjects with acute STEMI. Enrollment was 102. The study began on 2020-12-07, and primary completion was 2021-11-03.

The primary endpoint was hsCRP AUC from baseline through Day 14, analyzed with multiple imputation and reported as geometric least squares means with 95% confidence intervals. The reported least squares means ratio versus placebo was 0.58 for each RPH-104 dose group, with a 95% confidence interval of 0.37 to 0.91 in each comparison. Secondary measures included inflammation, fatal outcomes, hospitalization, heart failure, BNP, and end-diastolic volume. Safety counts were reported for serious and other adverse events and deaths.

Further details about the statistical plan, missing-data assumptions, multiplicity handling, and sample-size rationale are not reported in the registry record.