IL-1RA Treatment in Patients With Acute ACL Tear and Painful Effusions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IL-1RA Treatment in Patients With Acute ACL Tear and Painful Effusions (NCT02930122), a randomized phase 2 study. The primary outcome is Change of Knee Injury and Osteoarthritis Outcome Score (KOOS) Symptom Score Between Groups.

2. Clinical Question

The trial addressed an early treatment question after ACL injury. The registry describes pain, swelling, and inflammation as problems that can accompany these injuries, and states that the investigator aimed to reduce pre-operative pain and support earlier knee movement and preparation for surgery. It also describes interest in whether treatment soon after injury could affect later arthritis risk. However, the registered primary endpoint was change in KOOS Symptom Score between groups at 1 year; the registry record does not report a primary outcome result.

This distinction matters when interpreting the clinical question. The stated longer-term interest in arthritis is not the same as the registered primary endpoint. The registry lists a secondary outcome concerning change in CTX-II levels from injury to time of surgery, but does not report results for it. The clinical question that can be assessed from the registered endpoint is therefore a comparison of symptom-score change, not a demonstrated effect on later arthritis or on other outcomes.

The trial enrolled 6 participants and was terminated because of lack of funding. The registry says an insufficient number of participants were consented to generate meaningful data. Consequently, the record identifies the intended comparison but does not establish an outcome difference between anakinra and saline.

3. Trial Design

This was a phase 2, randomized, parallel-group, placebo-controlled study at a single center. The registry reports enrollment of 6 participants and lists two interventions: anakinra (150mg) and intra-articular saline. The anakinra arm description specifies an injection at 0-28 days post injury; the placebo description specifies a saline (0.9%) injection within 28 days of injury.

The official title calls the study triple-blinded, while the registry’s masking classification is double. These descriptions do not match, and the record does not explain the difference or specify which study roles were masked. The design is described as randomized, but details about sequence generation, allocation concealment, and implementation are not reported in the registry record. Those details would be needed to evaluate how the assignment process was carried out.

The study started on 2019-06-20, with primary completion listed as 2020-10-16. Its status is terminated. The registry attributes termination to lack of funding and says too few participants were consented to generate meaningful data. The record does not report a target enrollment or explain whether recruitment ended earlier than planned.

The primary outcome was change in KOOS Symptom Score between groups at 1 year. Four outcome measures are listed, including the secondary outcome of change in CTX-II levels from injury to time of surgery. The record lists no analyses. It does not report outcome estimates, uncertainty intervals, or hypothesis-test results. Thus, the design and intended outcomes can be described, but the comparative results cannot be evaluated from the registry record.

4. Participant Flow and Accounting

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

Before assignment: An insufficient number of participants were consented to generate meaningful data for this study as the study was terminated due to lack of funding.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The trial was terminated due to lack of funding so an insufficient number of participants were consented to generate meaningful data.

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: 6 participants had been enrolled at the time the study was closed (3 participants in each group)

6. Primary Endpoint

The registry lists the primary outcome as Change of Knee Injury and Osteoarthritis Outcome Score (KOOS) Symptom Score Between Groups, measured over 1 year.

The primary endpoint was change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Symptom Score between the groups at 1 year. The registry describes KOOS symptom scores as ranging from 0 to 100, with higher scores indicating less severe symptoms. The endpoint is therefore intended to represent a patient-reported assessment of knee symptoms, with change used to describe how the score varies over time.

Comparing change between randomized groups can address whether symptom scores changed differently under the two assigned interventions, subject to the trial’s size, conduct, and analysis. This endpoint focuses on symptoms rather than directly measuring structural arthritis or the biological mechanism of treatment. The registry’s separate secondary outcome, change in CTX-II levels from injury to time of surgery, concerns a biomarker and is not interchangeable with the primary symptom score.

The 1-year timeframe defines the intended assessment point. The registry does not report the actual KOOS values, change scores, group contrast, or a statistical analysis. It also says the study was terminated because of lack of funding and that too few participants were consented to generate meaningful data. Consequently, the endpoint’s meaning and direction can be described, but the degree or direction of any group difference cannot be determined from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to study groups using a chance-based process. In general, this can reduce systematic differences between groups at the time of assignment and helps make a comparison interpretable. It does not guarantee that small groups will have similar characteristics: chance imbalances can remain, especially when enrollment is limited. The registry identifies the study as randomized and parallel, but the sequence-generation method, allocation concealment, and assignment procedures are not reported in the registry record.

What does a parallel-group comparison mean?

In a parallel design, participants are assigned to a group and the groups receive their respective interventions during the study. This trial compared anakinra with saline placebo. The primary endpoint was change in KOOS Symptom Score between groups at 1 year. A suitable analysis would need to define how change is calculated, how participants are included, and how missing assessments are handled. Those details are not reported in the registry record, and the record lists no analyses or primary outcome estimates.

What does the KOOS score represent?

The registry describes KOOS symptom scores as ranging from 0 to 100, with higher scores indicating less severe symptoms. A score is a measurement, not a direct diagnosis or a direct measure of future arthritis. A change score summarizes movement from an earlier assessment to a later one, while a between-group comparison asks whether that movement differs between the assigned groups. The registry identifies the 1-year timeframe but does not report the observed scores, change values, or comparison.

How should an estimate and confidence interval be read?

In general, an effect estimate describes the size and direction of a comparison, while a confidence interval conveys the statistical uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval; an interval that includes values on both sides of no difference can be compatible with different underlying effects. These concepts cannot be applied to a trial-specific KOOS estimate because no estimate or interval is reported in the registry record. The record also provides no p-value for the primary outcome.

Why can small samples be difficult to interpret?

In general, results based on few participants are sensitive to the outcomes of individual participants and can be imprecise. Randomization does not remove that uncertainty. A small sample can also make it harder to assess whether the groups were balanced on important characteristics. Here, the registry reports enrollment of 6 and states that too few participants were consented to generate meaningful data. It does not report participant-level data or group outcome summaries that would allow further assessment.

What is the role of a planning illustration?

In general, sample-size planning asks how many participants might be needed to detect a specified effect under chosen assumptions. A calculation based on an observed effect is an illustration, not necessarily the design basis used before the trial began. If the observed effect comes from a small or unstable dataset, a planning calculation that relies on it may also be unstable. The registry’s stated assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The record does not report the trial’s own sample-size justification, nor does it give a primary effect estimate from which to judge a trial-specific illustration.

In general, “power” refers to the chance that a study would detect a specified effect under stated assumptions if that effect were present. A planning calculation is not the same as the probability that the trial’s finding is true, and it does not establish what the trial observed. No outcome analysis is listed in the registry record, so no observed power or outcome-based interpretation can be inferred. Sample-size illustrations should be read as planning scenarios, not as evidence about treatment effects.

Why do analysis choices matter?

Statistical results depend on choices such as the outcome definition, analysis population, handling of missing observations, and model assumptions. For count data, general methods may need to account for over-dispersion, meaning that variability exceeds what a simple model assumes; for continuous scores, distributional assumptions and the shape of residual variation may matter. These are general statistical considerations, not claims about the analysis used in this study. The registry does not report the statistical analysis plan, model, adjustment variables, or approach to missing data.

The record lists 4 outcome measures and 0 analyses. It therefore does not provide enough information to examine multiplicity procedures, model diagnostics, or robustness checks. The primary outcome was not reduced to a single reported comparison in the registry record. Without an estimate and its uncertainty, statistical significance, clinical importance, and precision cannot be assessed for the primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, time point, group comparison, or analysis. In general, testing many hypotheses can increase the chance of a nominally positive result arising by chance unless the analysis plan accounts for the testing structure. The registry lists four outcome measures, including the primary KOOS symptom-score change and the secondary CTX-II change from injury to time of surgery. It does not report a multiplicity adjustment, a prespecified hierarchy of outcomes, or a statistical analysis plan. The record therefore does not establish how multiple outcomes were intended to be interpreted.

Missing-data handling is also important because participants without an outcome assessment may differ from those with observed results. The registry says the trial was terminated for lack of funding and that too few participants were consented to generate meaningful data. It does not report how many participants completed the 1-year assessment, whether outcome data were missing, why any data were missing, or what methods would have been used to address missingness.

The record does not specify an analysis population, such as whether analyses were intended to include all randomized participants or another defined group. It also does not report an intention-to-treat approach, a per-protocol approach, or rules for exclusions. These are not details that can be inferred from randomization alone.

Because no analyses are listed, the registry record cannot show whether these issues affected a reported estimate. The absence of a reported result should not be interpreted as a null finding, nor does it establish equivalence between groups. It means the analysis and its handling of multiplicity and missing data are not available for assessment.

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 0% reporting threshold.

The registry lists two groups, each with 3 participants at risk. For each group, the serious adverse event count is 0, the other adverse event count is 0, and deaths are recorded as 0. These are counts reported for the participants included in each group, not estimates of risk in a wider population.

Zero recorded events in a small group does not demonstrate that the event cannot occur. With few participants, even a potentially relevant but uncommon event may not be observed. The figures also do not show how completely participants were monitored or whether all safety information was available for the same follow-up period. The registry record does not report adverse-event definitions, event collection procedures, or detailed safety analyses.

The group labelled “Arm 1” is not identified by intervention name in the adverse-event listing itself, while the other group is labelled “Placebo Control.” The record elsewhere describes an anakinra intervention and a saline placebo, but the adverse-event listing does not state the mapping for “Arm 1.” The counts should therefore be read as registry-reported group counts, not as evidence of a comparative safety difference.

These figures are descriptive. They cannot establish that either intervention is safe or unsafe, and they do not replace a larger or more complete safety assessment.

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

The registry record documents a randomized, placebo-controlled phase 2 study of anakinra versus saline in people with acute ACL tears and painful effusions. It specifies a primary endpoint of change in KOOS Symptom Score between groups at 1 year. It also records that the study was terminated because of lack of funding and that too few participants were consented to generate meaningful data.

What the record does not show is a treatment-effect estimate. There is no reported group difference in KOOS change, no uncertainty interval, and no primary-outcome analysis. Without those results, the direction, size, and precision of any difference cannot be assessed. The missing result is not evidence that the groups had identical outcomes; it leaves the comparison unresolved.

The stated interest in reducing pre-operative pain and exploring later arthritis risk should not be mistaken for evidence that either outcome changed. The registered primary endpoint concerns symptoms at 1 year, while the listed secondary outcome concerns CTX-II levels from injury to time of surgery. Neither outcome has a reported result in the registry record. No claim about a reduction in later arthritis can be drawn from the information recorded.

The adverse-event entries report no serious events, other events, or deaths among 3 participants at risk in each listed group. These counts are limited to the small enrolled groups and do not establish the absence of harms. They are not a substitute for a comparative safety analysis.

The trial can be understood as an attempt to study an early intervention using a randomized comparison, but the record does not provide the data needed to answer its primary statistical question. Conclusions should remain limited to the design, enrollment, termination explanation, intended outcomes, and recorded event counts. No conclusion about efficacy, equivalence, or long-term arthritis prevention is supported by these registry results.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a randomized design and an informative randomized result. Randomization is an important design feature, but the ability to answer a clinical question also depends on enrollment, outcome ascertainment, and reporting of the analysis. The registry reports that the trial enrolled 6 participants, was terminated for lack of funding, and did not obtain enough consented participants to generate meaningful data.

Statistically, this means the intended comparison cannot be judged from the registry record. A study can define a primary endpoint and comparator without producing an interpretable estimate of the difference. Without that estimate and its uncertainty, readers cannot assess how compatible the data are with different possible effects. In particular, an absent or unreported result is not equivalent to a result showing no difference.

The record also underscores why planning illustrations must be kept separate from study findings. A planning calculation can describe what might be required under assumptions, but it does not show that a trial reached its target or observed a treatment effect. The registry does not report the trial’s own sample-size justification or a primary effect estimate.

Finally, safety counts and efficacy outcomes answer different questions. The reported event counts are descriptive and limited to the enrolled participants, while the primary symptom comparison is not reported. Keeping these evidence types separate avoids treating small descriptive counts as proof of safety or the absence of an outcome estimate as evidence of no effect.

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 most important limitation recorded by the registry is that the trial was terminated because of lack of funding and that an insufficient number of participants were consented to generate meaningful data. Enrollment was 6. The registry reports no primary outcome estimate, group-level KOOS data, confidence interval, p-value, or analysis, leaving the primary comparison unresolved.

Several design and analysis details are not reported in the registry record. These include the randomization procedure, allocation concealment, the analysis population, the statistical model, missing-data methods, and any multiplicity strategy. The record does not give a sample-size justification for the trial. It also does not report participant characteristics or baseline outcome values, so group comparability cannot be examined.

The title describes the study as triple-blinded, but the masking classification is double. The record does not clarify this difference or identify which roles were masked. The adverse-event listing names “Arm 1” without identifying its intervention in that listing, limiting interpretation of group-specific safety counts.

The registry lists the primary endpoint at 1 year but does not report completion of that assessment. Follow-up completeness and reasons for missing outcome data are not reported. Although a secondary CTX-II outcome is listed, no results are provided. The stated interest in later arthritis is not accompanied by a reported arthritis outcome result in this record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: IL-1RA Treatment in Patients With Acute ACL Tear and Painful Effusions — NCT02930122.
• Registry record last updated 2021-11-24; status last verified 2021-10.
• Results first posted 2021-10-27.
• 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

NCT02930122 is a phase 2, randomized, parallel, placebo-controlled study of anakinra (150mg) versus intra-articular saline for people with acute ACL tears and painful effusions. Treatment was described as occurring within 28 days of injury. The primary endpoint was change in KOOS Symptom Score between groups at 1 year.

The registry reports enrollment of 6 and status as terminated. It attributes termination to lack of funding and states that too few participants were consented to generate meaningful data. No primary outcome analysis or comparative effect estimate is reported. The record lists four outcome measures and no analyses.

For each of the two listed groups, the registry records 0 serious adverse events, 0 other adverse events, and 0 deaths among 3 participants at risk. These descriptive counts do not establish comparative safety. Overall, the record documents the study’s intended design and outcomes but does not provide results that answer the primary clinical question.