Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis (NCT04017936), a randomized phase 2 study. The primary outcome is Change in Inflammation Marker.

2. Clinical Question

The question is about a short-term change in an inflammation marker, rather than a direct measure of cardiac function, clinical events, or long-term disease course. The record also lists change in cardiac fibrosis as a secondary outcome, but numerical results for that outcome are not reported in the registry record.

This is a clinical trial question, but the posted information does not establish whether the groups were comparable at baseline, how participants were selected, or how other treatments were managed. Those details matter when interpreting group differences. In particular, the comparator is described only as continued standard of care, so the record does not identify a single uniform treatment against which anakinra was tested.

3. Trial Design

The study is registered as a randomized, parallel-group Phase 2 trial with no masking. It is marked completed. The registry reports enrollment of 17, a start date of 2020-10-23, and primary completion on 2024-06-30. These registry fields describe the study’s status and enrollment, but do not by themselves establish how many participants contributed to each outcome analysis.

The intervention group received Anakinra, described as a 100 mg/0.67 mL daily subcutaneous injection for 4 weeks. The comparison group continued standard of care treatment. The trial record does not specify the standard of care regimens used by participants, whether treatment changes were permitted, or whether adherence was assessed.

For the primary outcome, the posted group summaries list 6 participants in the Anakinra analysis and 10 in the Standard of Care analysis. The registry notes that Patient 5 was excluded from the Anakinra group outcome analysis. The reason for this exclusion and any other details about the analysis population are not reported in the registry record. The enrollment field and the outcome-analysis group counts refer to different registry information; the record does not explain the relationship between them.

Randomization can help balance prognostic factors across groups on average, while open-label treatment means masking was absent. The record does not report the randomization procedure, allocation concealment, or whether outcome measurement was blinded. It also does not report a detailed protocol, a sample-size justification for the trial, or the planned statistical analysis. Those gaps limit assessment of the design beyond the registry fields and descriptions.

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

Analysis population for the primary outcome, as defined in the registry: Patient 5 excluded from Anakinra group outcome analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Inflammation Marker, measured over Baseline to 28 days.

The primary outcome is titled “Change in Inflammation Marker.” It measures change in C-reactive protein in participant plasma samples, with the timeframe stated as baseline to 28 days. The unit is mg/L, and the outcome is summarized as a mean with a standard deviation for each group.

In general, C-reactive protein is a blood marker associated with inflammation. A marker can be useful for tracking a biological response over time, but a change in a marker is not itself a direct measure of how a person feels or functions, nor does it necessarily capture changes in the heart specifically. The registry describes the sample as participant plasma but does not report assay details or a sign convention for calculating change.

The posted mean change is -43 mg/L in the Anakinra group and 7 mg/L in the Standard of Care group. Their standard deviations are 36.0 and 41.56, respectively. These are separate group summaries. The registry record does not post a confidence interval or a statistical test for the between-group contrast, so the precision of that contrast and the strength of evidence for a difference cannot be assessed from these values alone.

The record lists change in cardiac fibrosis as a secondary outcome, but its numerical result is not reported in the registry record. The primary marker result therefore should be read as a short-term summary of the recorded C-reactive protein change, not as a complete account of all outcomes relevant to cardiac sarcoidosis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it records a quantity in mg/L, and the registry identifies the summary measure as a mean. A mean describes the average observed change within a group. The standard deviation describes how spread out individual values are around that group mean. These statistics answer different questions: the mean describes the group’s central value, while the standard deviation describes variation among observed values.

For the primary outcome, the posted mean changes are -43 mg/L for Anakinra and 7 mg/L for Standard of Care. Their posted standard deviations are 36.0 and 41.56. These summaries are not themselves a direct estimate of the difference between treatment groups. A between-group analysis would ordinarily estimate a contrast and quantify its uncertainty, but the registry record does not report such an estimate for this outcome.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. For a treatment-group contrast, it helps show both the estimated direction and the precision of that contrast. A narrow interval generally indicates greater precision than a wide one, although precision is not the same as clinical importance. No confidence interval for the primary between-group contrast is reported in the registry record.

What does the standard deviation tell us?

In general, a standard deviation describes the spread of participant-level observations around the mean. It does not directly provide the uncertainty in the mean or in a contrast between means. To quantify uncertainty in a contrast, an analysis needs to account for the group sizes, the observed variation, and the chosen statistical model. The registry posts group sizes and standard deviations but does not post a comparison estimate or its uncertainty.

Why can over-dispersion matter?

In general, over-dispersion means that observations vary more than a statistical model assumes. If a model understates variability, its uncertainty estimates can be too small and statistical evidence can appear stronger than warranted. This concept is particularly relevant for counts or other outcomes where the assumed variability may not match the observed data. The primary outcome is continuous and summarized by means and standard deviations; the registry record does not report a model or an over-dispersion assessment for it.

What is missing from the reported comparison?

The results information indicates that values were missing or not estimable for a two-arm comparison of the continuous endpoint. It does not report an inferential comparison for the primary outcome. The absence of a comparison means readers cannot use the registry record to assess a reported p-value, confidence interval, or model-based estimate for the contrast. It is not appropriate to derive a new contrast or test from the separate summaries and present it as the trial’s analysis.

The primary outcome is measured from baseline to 28 days. In general, analysis of change scores summarizes how measurements move over time, but interpretation depends on how change is defined, how baseline values are handled, and whether data are available at the relevant timepoints. The registry describes the outcome as change in C-reactive protein but does not report the formula used to calculate change, the distribution of baseline values, or a detailed approach to missing measurements.

The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These assumptions concern planning illustrations, not the trial’s own reported design justification or observed power. The sample-size justification for the trial is not reported in the registry record. A planning calculation based on an observed effect is sensitive to the effect chosen and does not show that the trial had a specified probability of detecting an effect after the data were collected.

Randomization is a design method for assigning participants to groups, with the aim of reducing systematic differences in prognostic factors. In general, randomization does not ensure that groups are identical, especially in a small trial, and it does not replace a clear description of allocation procedures or outcome analysis. The registry identifies the study as randomized but does not report the method used to generate assignments or how allocation was concealed.

Because masking is listed as none, treatment assignment was not masked according to the registry. In general, masking can reduce the potential for expectations to influence treatment, participant reporting, or outcome assessment. The record does not state whether outcome assessment was independently blinded despite the overall masking field. No detailed statistical plan or interim analysis information is reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Anakinra", "Standard of Care")
n   <- c(6, 10)
m   <- c(-43, 7)
sp  <- c(36, 41.56)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Anakinra  6  -43.000  36.000  -80.780  -5.220
CARM  Standard of Care  10  7.000  41.560  -22.730  36.730

11. Multiplicity, Missing Data and Analysis Populations

The record lists change in inflammation marker as the primary outcome and change in cardiac fibrosis as a secondary outcome. The secondary outcome is named, but its numerical result is not reported in the registry record. The registry results information lists no analyses. It does not report whether multiple outcomes were formally tested, whether any adjustment for multiple testing was planned, or how outcome priority was handled in the analysis.

Multiplicity arises in general when several outcomes or several statistical tests are considered: the chance of at least one apparently notable result can increase as more tests are performed. Statistical plans sometimes address this through prespecified outcome hierarchies or adjustment procedures. Such procedures are not described in the registry record, so the handling of multiplicity cannot be evaluated.

The registry notes that Patient 5 was excluded from the Anakinra group outcome analysis. The reason for the exclusion, whether the participant had a missing measurement, and whether the exclusion followed a prespecified rule are not reported in the registry record. The record does not describe imputation, sensitivity analyses, or a complete-case or intention-to-treat analysis population. It also does not explain whether other missing outcome data occurred.

These omissions do not show that no analysis or missing-data procedure was used; they mean the registry record does not report enough information to assess those procedures. The posted summaries should therefore be understood as applying to the analyzed outcome groups as recorded, without assuming that they represent every enrolled participant or that missingness had no effect.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalized for a diabetic foot infection (14.3%).

The safety figures are recorded separately by group. For serious adverse events, the Anakinra group lists 1 affected participant among 7 at risk, and the Standard of Care group lists 0 among 10 at risk. The record lists 0 deaths in each group. These are counts in the registry’s safety fields and should not be read as estimates of the comparative safety of the treatments.

For other adverse events, the record lists 7 affected among 7 at risk in the Anakinra group and 9 among 10 at risk in the Standard of Care group. The registry lists “hospitalized for a diabetic foot infection” as the top serious adverse event term, with 14.3%. The record does not provide enough detail in these fields to determine the full clinical context, timing, duration, or relationship of an event to treatment.

In general, an at-risk count gives the group size used for the event summary, while an affected count records how many were reported as having the event. Event counts do not establish that treatment caused an event. The registry record also does not describe the process for collecting or adjudicating adverse events. With these limitations, the figures are best read as descriptive safety reporting for this trial, not as a definitive comparison.

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

The registry record shows group-level summaries of change in C-reactive protein from baseline to 28 days. The Anakinra group mean is -43 mg/L, with a standard deviation of 36.0; the Standard of Care group mean is 7 mg/L, with a standard deviation of 41.56. These figures describe the analyzed outcome groups and the variation in their observed values.

The record does not report a statistical comparison of the groups for this endpoint, including a confidence interval or p-value. The posted results therefore do not establish the precision of a between-group contrast. Separate group means cannot substitute for a reported contrast and its uncertainty, and no new contrast should be inferred from these summaries as if it were the trial’s analysis.

The endpoint is a short-term inflammation marker, not a direct measure of cardiac function, symptoms, or long-term outcomes. The registry record does not report numerical results for the listed secondary outcome, change in cardiac fibrosis. It also does not report whether changes in the marker corresponded to changes in other clinical measures.

The safety information records serious and other adverse events, as well as deaths, by group. These event counts are descriptive and do not establish whether an event was caused by treatment or whether risk differed between groups. The registry does not provide detailed event timing or adjudication information.

These findings should not be treated as proof for or against a treatment effect. The trial record is limited by a small enrollment, a primary outcome analysis that excludes Patient 5 from the Anakinra group, and incomplete reporting of the analysis plan and missing-data handling. The registry’s planning assumptions are not evidence of observed power. The available record supports a description of the posted measurements and events, but not a definitive clinical conclusion.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between descriptive summaries and an inferential comparison. The registry reports a mean and standard deviation for each group, but does not report a between-group estimate or its uncertainty for the primary outcome. Without that comparison, readers cannot assess how precisely the groups differ on the recorded scale.

The record also makes the analysis population important to interpretation. It reports enrollment of 17, while the primary outcome summaries list 6 participants in the Anakinra analysis and 10 in the Standard of Care analysis, and notes that Patient 5 was excluded from the Anakinra outcome analysis. The registry does not explain the relationship between enrollment and these outcome counts or the reason for the exclusion. Clear accounting of who contributed data is essential for evaluating the scope of a result.

Another statistical issue is the distinction between an outcome and its clinical meaning. C-reactive protein is an inflammation marker, and the primary endpoint captures change in that marker over a short timeframe. It does not, by itself, establish a change in cardiac function or other clinical outcomes. The registry lists change in cardiac fibrosis as secondary, but numerical results are not reported.

Finally, the registry’s planning assumptions should be separated from evidence generated by the trial. Planning illustrations based on an observed effect are not observed power and do not resolve uncertainty in the reported outcome. The missing comparison, analysis details, and secondary result limit what can be inferred from the posted record, regardless of the direction of the group summaries.

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 registry identifies a randomized, open-label design but does not report the randomization procedure, allocation concealment, or whether outcome assessment was blinded. The intervention description gives the Anakinra regimen, while the comparator is described only as continued standard of care. The particular care regimens and any changes during follow-up are not reported in the registry record.

The primary outcome analysis excludes Patient 5 from the Anakinra group. The reason for exclusion and the rules governing analysis populations are not reported. Although group sizes and summary statistics are posted, the registry does not describe baseline comparability, the calculation of change, or the handling of missing measurements. It also does not report an inferential comparison, confidence interval, or p-value for the primary endpoint.

The record lists change in cardiac fibrosis as a secondary outcome but does not report its numerical result. It does not describe adjustments for multiple outcomes, interim analyses, or a detailed statistical plan. The sample-size justification for the trial is not reported in the registry record. The listed planning assumptions are illustrations and should not be mistaken for a documented rationale for the trial’s enrollment.

The safety fields provide counts but limited context about event timing, duration, adjudication, or treatment relationship. The brief summary describes the rationale for studying cardiac sarcoidosis, but the registry results do not provide detailed participant characteristics or enough information to assess generalizability. These reporting limitations constrain interpretation of both the primary outcome and safety figures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis — NCT04017936.
• Registry record last updated 2025-08-07; status last verified 2025-08.
• Results first posted 2025-08-07.
• 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 record describes a completed, randomized, parallel-group, open-label Phase 2 trial of Anakinra for cardiac sarcoidosis. Reported enrollment is 17. The intervention was a 100 mg/0.67 mL daily subcutaneous injection for 4 weeks; the comparison group continued standard of care treatment.

The primary outcome was change in C-reactive protein in participant plasma samples from baseline to 28 days, summarized as a mean and standard deviation. The posted means are -43 mg/L for Anakinra and 7 mg/L for Standard of Care. Patient 5 was excluded from the Anakinra outcome analysis. The registry record does not report an inferential comparison for the primary outcome.

Change in cardiac fibrosis is listed as a secondary outcome, but its numerical result is not reported in the registry record. Safety fields list serious and other adverse events and deaths by group. The record does not report a detailed statistical plan, missing-data methods, or a trial sample-size justification.