Success of Long-acting Anti-inflammatories After Anterior Cruciate Ligament and Meniscal Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Success of Long-acting Anti-inflammatories After Anterior Cruciate Ligament and Meniscal Injury (NCT04331002), a randomized phase 2 study. The primary outcome is Change in Bone Shape (Baseline to 4 Months).

2. Clinical Question

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group Phase 2 study. Its title is “Success of Long-acting Anti-inflammatories After Anterior Cruciate Ligament and Meniscal Injury.” The brief summary frames the purpose as determining whether extended-release triamcinolone acetonide alters progressive bone-shape changes previously demonstrated after ACL reconstruction with partial meniscectomy or meniscal repair. The listed conditions include meniscal injury and anterior cruciate ligament tear.

The experimental arm was described as receiving a single 32 mg Zilretta injection approximately 8 weeks after meniscus surgery. The placebo arm was described as receiving a single 5 mL normal-saline injection at approximately the same postoperative timing. These are arm descriptions in the registry; the record does not report whether the enrolled participant received either injection, or the participant’s arm assignment.

The study started on 2020-08-21, and the listed primary completion date is 2022-07-11. Its status is terminated. Enrollment is reported as 1. The registry does not report why the study was terminated, whether the termination was planned, or whether the planned recruitment target changed. It also does not report the allocation sequence or how masking was implemented. The quadruple-masked label identifies the stated design, but the record does not specify which groups of people were masked or whether masking was maintained.

The small enrollment has a direct consequence for interpretation: the registry says that participant-level primary outcome data cannot be presented because the participant could reasonably be identified. Although the record lists 11 outcome measures, it reports zero analyses. Thus, the posted record describes the design and intended assessments but does not offer an estimable treatment comparison. Further details about recruitment, treatment exposure, protocol conduct, or reasons for termination are not reported in 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: One participant was enrolled in this study. Due to the possibility that the participant could reasonably be identified due to low enrollment, data cannot be presented.

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: Research cancelled and 0 participants enrolled in Arm 2

6. Primary Endpoint

The registry lists the primary outcome as Change in Bone Shape (Baseline to 4 Months), measured over Baseline, 4 months.

The registered primary endpoint is change in bone shape from baseline to 4 months, operationalized as change in medial femoral condyle volume. The registry describes manual segmentation of 3-Tesla MRI scans performed before the study injection and 4 months after it. The volume is expressed as cm3. The outcome title and description therefore focus on a structural imaging measure rather than a patient-reported symptom or functional score.

In general, a quantitative imaging measure can provide a defined way to track structural features over time. Measuring the same anatomical feature at baseline and follow-up can describe within-participant change, while a randomized comparison is intended to assess whether changes differ between assigned groups. This general rationale does not establish that a structural change predicts symptoms, function, later injury, or benefit to participants. Such relationships are not reported in the registry record.

The choice of medial femoral condyle volume aligns with the study’s stated interest in progressive bone-shape changes after ACL reconstruction and meniscus surgery. The record does not explain how manual segmentation was standardized, whether image readers were masked, how segmentation reliability was assessed, or how the change measure would be analyzed. Most importantly, it withholds the participant’s primary outcome data because of identification risk. No baseline value, follow-up value, change estimate, or treatment-group contrast is available in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Random assignment is intended to make treatment groups comparable, on average, with respect to factors that could influence outcomes. In general, when allocation is successfully implemented and outcomes are analyzed as planned, a between-group comparison can support an estimate of the treatment effect. Randomization does not guarantee balance in every realized study, and the record does not report the allocation sequence, participant assignment, or an analysis. With enrollment of 1, the registry does not provide a treatment contrast that can be evaluated.

What does masking contribute?

In general, masking can reduce the influence of expectations on treatment delivery, outcome assessment, or participant reporting. The registry labels the design quadruple-masked, but does not identify the people intended to be masked, explain how masking was maintained, or report whether it was successful. The label alone cannot establish that assessments or care were unaffected by knowledge of assignment. Manual segmentation of MRI is part of the primary outcome measurement, but reader masking and procedures for checking segmentation consistency are not reported in the registry record.

What would a change score represent?

The registered endpoint is change in medial femoral condyle volume from baseline to 4 months. In general, a change score uses measurements at multiple times for the same participant to describe movement from the initial value. A randomized analysis could compare those changes between the assigned groups, or could use another prespecified approach to account for baseline values. Which approach was planned is not reported. Since the record withholds the outcome data, no change score or comparison can be interpreted.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the data and the statistical model, and its width reflects precision. A point estimate without an interval can obscure substantial uncertainty; an interval that includes values on different sides of a null effect may remain compatible with different conclusions. These concepts cannot be applied to a treatment estimate in this record because no estimate or interval is reported. No p-value is reported either. The zero analyses listed in the record are consistent with the absence of a posted analysis, not a finding that a statistical test was nonsignificant.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. It also distinguishes total events for time-to-event planning from participants per arm for other planning. These are general planning assumptions, not evidence of the study’s own design or a record of achieved power. The registry does not report its sample-size justification, and the observed primary effect needed for such illustrations is unavailable. The illustrations cannot be interpreted as showing what this trial could detect based on an observed outcome.

In general, an observed effect is a study estimate, while power is a planning probability under specified assumptions. A post hoc calculation using an observed estimate does not establish the probability that the study detected a real effect, and it cannot replace a reported estimate with its uncertainty. Here, the lack of a disclosed primary outcome prevents readers from evaluating the magnitude or variability of the measured change. The planning assumptions do not fill that gap.

Why can over-dispersion matter?

In general, over-dispersion occurs when outcome variability exceeds what a chosen statistical model assumes. If unaccounted for, standard errors and uncertainty intervals can be too small, making results look more precise than warranted. That issue is relevant when selecting models for outcomes whose variability may not match a simple distributional assumption. The registry does not report an analysis model, outcome distribution, or evidence of over-dispersion, so it is not possible to say whether this issue arose or how it was handled.

Other method details are also absent: the planned estimand, the handling of missing observations, any covariate adjustment, assumptions about repeated measurements, and sensitivity analyses are not reported in the registry record. These omissions limit methodological appraisal independently of the withheld data. They do not justify guessing which methods investigators intended to use.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary bone-shape outcome and secondary changes in IKDC, KOOS Global, and ICOAP. Multiple outcomes and follow-up times create a general multiplicity issue: when many statistical questions are tested, the chance of obtaining an apparently notable result by chance can rise. In general, a prespecified strategy may distinguish a primary question from secondary or exploratory questions and may adjust or otherwise account for multiple comparisons. The registry does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any adjustment was planned.

Missing-data methods are not reported in the registry record. The record does not say whether all planned assessments were collected, how unavailable MRI or questionnaire measurements would be handled, or whether sensitivity analyses were planned. With the primary participant data withheld for identification reasons, readers cannot assess completeness, describe missingness, or evaluate assumptions used in an analysis.

The record also does not report analysis populations, such as whether the intended analysis would follow randomized assignment or require treatment receipt. It does not report exclusions, protocol deviations, or the population used for any analysis; zero analyses are listed. Consequently, neither an intention-to-treat comparison nor a per-protocol comparison can be attributed to this study’s posted results.

These gaps matter because outcome selection, missingness, and analysis population can affect both the estimate and its interpretation. The record does not permit an appraisal of how these issues were addressed.

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

The record establishes that investigators planned a randomized comparison of extended-release triamcinolone acetonide with saline placebo after meniscus surgery, with bone-shape change as the primary question. It also records a single enrolled participant, a terminated study, and a primary endpoint based on medial femoral condyle volume measured with MRI. Those details describe the intended study and the limited information available; they do not provide a treatment effect.

The central boundary is that the primary outcome data were not presented because the participant could reasonably be identified given low enrollment. A missing result is not a null result. It cannot show that the intervention and placebo produced equal changes, that either group changed, or that a clinically important difference was absent. No estimate or uncertainty interval is available to support those claims.

The same caution applies to secondary outcomes and safety. The registry names patient-reported outcomes but posts no analyses. Its adverse-event entries contain zero values for the listed groups, including zero at risk; without evidence of assignment or exposure, these entries do not establish the absence of adverse events among treated participants.

Nor do the planning assumptions establish observed power, the adequacy of the sample size, or the trial’s original design rationale. The record does not report a sample-size justification. The study’s termination status alone does not explain its reasons or consequences. Interpretation should therefore remain descriptive: this record documents an intended clinical question and an outcome that cannot be evaluated from the posted data.

12. Why This Trial Matters Statistically

This study illustrates an important distinction between a registered clinical question and an answerable statistical comparison. A clear endpoint and a randomized design can define what investigators intend to estimate, but an estimate still requires interpretable outcome data and information about assignment. Here, the registry describes the intended comparison and endpoint, yet reports enrollment of 1, lists zero analyses, and withholds the primary outcome data for identification reasons.

That situation matters for readers evaluating trial evidence. It prevents assessment of effect direction, effect size, precision, and consistency across imaging and patient-reported outcomes. It also shows why missing results should not be treated as proof of no effect. An absent estimate leaves uncertainty unresolved rather than locating the effect near a particular value.

The record also demonstrates the importance of distinguishing study-specific analysis plans from general planning assumptions. The stated planning assumptions do not establish the original sample-size rationale or show achieved power. When the observed effect is unavailable, effect-based planning illustrations cannot provide an independent result. This is particularly important for interpreting small or terminated studies, where estimates and their uncertainty may be difficult to assess even when reported.

Finally, the inability to present participant data because of identification risk highlights a real tension between privacy and transparency. The record communicates the reason for withholding data, but that necessary protection also leaves the primary question unanswered in the public record. For statistical interpretation, clear disclosure of what is known and what cannot be inferred is essential.

13. 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 consequential limitation is the registry’s explicit statement that primary outcome data cannot be presented because the participant could reasonably be identified due to low enrollment. The study enrolled 1 participant, so no public estimate of change or treatment comparison is available. This prevents evaluation of both the magnitude and precision of the primary outcome.

The study is listed as terminated, but the reason for termination and whether it was related to recruitment, feasibility, safety, or another issue are not reported in the registry record. The record also does not say whether the participant was assigned to an arm, received an injection, or completed the planned MRI and secondary assessments. These details should not be inferred from the arm descriptions or enrollment entry.

Although the design is labeled randomized, quadruple-masked, and parallel, the record does not report the allocation procedure, masking roles, success of masking, or treatment adherence. It does not describe the manual segmentation protocol, image-reader reliability, or statistical analysis method. Sample-size justification, handling of missing data, analysis populations, and multiplicity procedures are also not reported.

The listed adverse-event counts do not permit a meaningful safety assessment because the registry reports zero participants at risk in both groups and does not document treatment exposure. Secondary outcomes are named but no results are reported. These limitations mean that the record offers a description of intent, rather than interpretable evidence about clinical or structural outcomes.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Success of Long-acting Anti-inflammatories After Anterior Cruciate Ligament and Meniscal Injury — NCT04331002.
• Registry record last updated 2023-07-27; status last verified 2023-07.
• Results first posted 2023-07-27.
• 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.

17. Record Summary

The registry describes a randomized, quadruple-masked, parallel-group Phase 2 study of extended-release triamcinolone acetonide versus saline placebo after meniscus surgery in people with ACL and meniscal injury. The experimental arm was described as receiving a single 32 mg Zilretta injection, and the placebo arm a single 5 mL saline injection, approximately 8 weeks after surgery.

The primary endpoint was change in medial femoral condyle volume from baseline to 4 months, measured using manual segmentation of 3-Tesla MRI scans. Enrollment is reported as 1, and the study status is terminated. The record states that primary outcome data cannot be presented because the participant could reasonably be identified. It lists 11 outcome measures and zero analyses. No primary or secondary result, treatment comparison, or interpretable safety assessment is posted. The reason for termination and further analysis details are not reported in the registry record.