This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for nSTRIDE APS Versus Hyaluronic Acid for Knee Osteoarthritis (NCT03182374), a randomized na study. The primary outcome is Change From Baseline to 12 Months Post-injection in Mean WOMAC LK3.1 Pain Score in Both Arms of the Study (nSTRIDE APS and Synvisc One).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03182374 |
| Phase | NA |
| Condition | Osteoarthritis, Knee |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 252 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Zimmer Biomet |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with painful knee osteoarthritis. Its brief summary describes participants with painful unilateral knee osteoarthritis who had not achieved satisfactory pain relief with previous conservative osteoarthritis treatment. The registry record says that eligibility also depended on specific inclusion and exclusion criteria, but does not report those criteria in the information available for this analysis.
Intervention
One intervention was nSTRIDE APS, an autologous protein solution prepared from a small blood sample using a point-of-care kit and injected into the knee joint. The registry describes the kit as intended for rapid preparation of APS. Details of the injection schedule are not reported in the registry record.
Comparator
The comparator was Synvisc-One, a hyaluronic acid product intended for injection into the knee joint. The study description refers to comparing APS with intra-articular hyaluronic acid injections. The registry record does not provide further details about the treatment sequence or the timing of injections in each phase.
Primary question
The stated primary outcome was change from baseline to 12 months in mean WOMAC LK3.1 pain score in both treatment arms. The clinical question is whether the recorded pain-score changes differ between the APS and Synvisc-One treatment conditions. The numerical arm results and a between-treatment estimate are not reported in the registry record, so the direction and size of any contrast cannot be described.
3. Trial Design
NCT03182374 is listed as a completed, randomized, multicenter study with a crossover model. The official title describes a two-phase comparison of autologous protein solution and hyaluronic acid injections in people with knee osteoarthritis. The registry lists nSTRIDE APS and Synvisc-One as the interventions. Although the crossover designation indicates that the study was organized around more than one treatment phase, the sequence assigned to participants, the length of each phase, and any washout procedures are not reported in the registry record. Those details matter when interpreting crossover outcomes because observations may depend on treatment order, time, or carryover from an earlier phase.
The registry record lists quadruple masking, while the brief summary describes the study as double-blind. These descriptions are not identical, and the record does not explain the distinction or identify which roles were masked. The record lists enrollment as 252, whereas the brief summary states that a total of 246 patients will be enrolled. Both figures are reported in the registry, but their relationship is not explained. The study start date is 2017-07-14, and the primary completion date is 2019-09-30. The registry lists a maximum study duration of 50 months for each subject, including 48 months from treatment to last follow-up and two additional months if the maximum visit window is realized. These planned duration details do not establish how long participants were actually followed.
The study description says that the primary outcome used an intention-to-treat population with imputations for missing data. Further details of the analysis, including how the crossover structure was handled, are not reported in the registry record. No conclusion about the actual treatment comparison follows from the design description alone.
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: Subjects giving written informed consent underwent screening assessments including demographics, medical history, physical examination, knee examination, a urine pregnancy test (if applicable) and the WOMAC LK 3.1. Upon confirmation of eligibility, subjects were scheduled for a treatment visit, and a baseline X-ray and MRI were performed.
Overall Study
| Stage | nSTRIDE APS | Synvisc-One |
|---|---|---|
| STARTED | 125 | 127 |
| Treated | 124 | 127 |
| 12-month Follow-up | 111 | 106 |
| COMPLETED | 111 | 106 |
| NOT COMPLETED | 14 | 21 |
Reasons for not completing this period:
| Reason | nSTRIDE APS | Synvisc-One |
|---|---|---|
| Lost to Follow-up | 3 | 2 |
| Lack of Efficacy | 8 | 14 |
| Withdrawal by Subject | 1 | 1 |
| exit for non-compliance | 1 | 1 |
| one subject was randomized but not treated | 1 | 0 |
| Other reasons | 0 | 3 |
Analysis population for the primary outcome, as defined in the registry: ITT population, with imputations for missing 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.
| Characteristic | Unit | nSTRIDE APS | Synvisc-One | Total |
|---|---|---|---|---|
| Participants analysed | 125 | 127 | 252 | |
| Age, Continuous | years | 58.9 (SD 10.52) | 57.9 (SD 10.82) | 58.9 (SD 10.5) |
| Sex: Female, Male: Female | Participants | 75 | 78 | 153 |
| Sex: Female, Male: Male | Participants | 50 | 49 | 99 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| BMI | kg/m^2 | 28.20 (SD 4.211) | 27.53 (SD 4.217) | 27.86 (SD 4.214) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to 12 Months Post-injection in Mean WOMAC LK3.1 Pain Score in Both Arms of the Study (nSTRIDE APS and Synvisc One), measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline to 12 months in the mean WOMAC LK3.1 pain score for the nSTRIDE APS and Synvisc-One arms. WOMAC is a self-administered questionnaire used to evaluate hip and knee osteoarthritis. It contains separate pain, stiffness, and physical-function subscales; this endpoint concerns only the pain subscale. The pain subscale has a possible score range of 0-20, with higher scores indicating worse pain. The registry describes the measure as a score on a scale and reports the mean and standard deviation as the summary measures.
Using a change score focuses on how a participant’s recorded pain score differs from their own baseline value over the specified follow-up period. Comparing the arm-level changes can help describe how the two treatment conditions differ on the chosen measure. The mean conveys the average score change, while the standard deviation describes variability among observations; it is not itself a measure of uncertainty in the mean or in the treatment contrast.
The registry record does not report the mean change in either arm, the standard deviations, or a direct estimate of the difference between treatment conditions. It also does not report a confidence interval or p-value for this endpoint. Therefore, the endpoint’s definition is available, but the magnitude and precision of the observed result are not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically interpretable outcome: change in WOMAC pain score from baseline to 12 months. However, it does not report the numerical results needed to describe the observed change in either treatment arm or the contrast between APS and Synvisc-One. Without those values, it is not possible to say which arm had a larger mean change, how large a difference was observed, or how uncertain that difference was. No conclusion about the direction or size of the treatment comparison should be drawn from the endpoint description alone.
The endpoint is a continuous measure. A mean change would describe the average change in score, and a standard deviation would describe how spread out individual changes were around that average. To assess the comparison, readers would also need a direct between-treatment estimate and a measure of its uncertainty, such as a confidence interval. A confidence interval expresses a range of estimates compatible with the data and the statistical model; its width helps show the precision of the estimate. Neither an interval nor another numerical measure of precision is reported for the primary outcome in the registry record.
The crossover model is relevant to interpretation because outcomes may depend on treatment order, phase, or effects carried forward from an earlier treatment period. A crossover analysis should account for the design when estimating treatment differences. The registry record does not describe the treatment sequences, washout arrangements, or statistical handling of period and sequence effects. It is therefore not possible to assess from the record whether those features were incorporated into the primary analysis.
The record says that the primary analysis population was intention-to-treat, with imputations for missing data. This identifies a broad analysis approach, but does not specify how missing observations were imputed or how the analysis retained participants in their assigned groups. The numerical outcome estimates are not reported, so the influence of missing data on the result cannot be evaluated.
The registry lists six outcome measures and six analyses, but does not report how the analyses were prioritized or whether multiplicity was addressed. Multiple outcomes or analyses can increase the chance of at least one apparently noteworthy result if each is interpreted independently. Without an analysis plan or reported adjustment approach, the statistical interpretation of findings across outcomes would require caution. In this record, however, the more basic limitation is that the primary numerical comparison itself is not reported.
Safety summaries are available separately, including counts of participants affected by serious and other adverse events. Those counts describe reported safety experience in the listed groups, but do not substitute for the missing primary efficacy estimates. Taken together, the registry supports a description of the study question, design, endpoint, and some safety counts, but not an estimate of the primary treatment effect.
9. Statistical Methods Explained
The endpoint is continuous because it is a score that can take values across a defined scale. The registry specifies the mean as the summary measure and standard deviation as the measure of dispersion. The mean is the arithmetic average of the observations in an analysis group. The standard deviation describes how much individual values vary around that average. It is important not to interpret the standard deviation as the precision of the average or of a difference between groups. Precision is usually assessed using a standard error, confidence interval, or another inferential quantity.
The primary endpoint is a change score: the score at follow-up is considered relative to baseline. This can make a result easier to interpret as change over time, but a change score still needs a clear comparison. Arm-specific changes describe what happened within each treatment condition; a between-treatment contrast describes how those changes differ. The registry record names the outcome in both arms but does not report the arm-specific estimates or the between-treatment contrast. It also does not report an inferential test or confidence interval for this endpoint.
What does randomization contribute?
Randomization is intended to create treatment groups that are comparable on average before treatment, including with respect to factors that may not have been measured. It supports a causal comparison when the study is conducted and analyzed in line with its randomized design. The registry lists randomized allocation, but does not report the randomization procedure, allocation concealment details, or the sequence in which crossover treatments were assigned. Those details are not reported in the registry record and should not be assumed.
Masking can reduce the influence of expectations or knowledge of treatment assignment on care, reporting, and outcome assessment. The registry lists quadruple masking, while its brief summary calls the study double-blind. The record does not clarify who was masked or why the descriptions differ. Consequently, the masking description can be reported, but its implementation cannot be evaluated from the record.
Why does the crossover model matter?
In a crossover study, participants may receive more than one treatment across distinct phases. Each participant can therefore contribute information under more than one treatment condition, and within-participant comparisons may be part of the analysis. Such designs require attention to the assigned sequence, time or period effects, and possible carryover from an earlier treatment. The registry record does not report the sequences, phase timing, washout procedures, or model used to account for these features. It is not possible to determine how the analysis handled the crossover structure.
The record gives the primary analysis population as intention-to-treat, with imputations for missing data. In general, intention-to-treat analysis aims to preserve participants in the groups to which they were assigned, rather than basing the comparison only on treatment received or adherence. The record does not explain how this principle was applied to the crossover phases. Imputation replaces missing outcome values with estimates under a specified method. Different methods rely on different assumptions, so the method and assumptions matter when assessing the robustness of results. Neither is reported in the registry record.
How should uncertainty be assessed?
A point estimate gives a single summary of an observed contrast. A confidence interval adds information about uncertainty by showing a range of values compatible with the data and the analysis assumptions. A narrow interval indicates greater precision than a wide interval, while the interval’s position relative to a value of no difference helps readers assess the range of plausible contrasts. These are general statistical concepts. The registry record does not report a primary treatment estimate or its confidence interval, so uncertainty about the primary comparison cannot be quantified from the record.
Statistical significance and clinical importance are different questions. A p-value, when reported, describes how compatible the data are with a specified null hypothesis under the statistical model; it does not measure the size or importance of an effect. Clinical interpretation also requires the scale, the direction of scoring, the estimated contrast, its precision, and an appropriate basis for judging meaningful change. The record defines the WOMAC pain scale and its direction, but does not report the primary numerical estimate or a threshold for meaningful change.
What do the planning assumptions mean?
The registry’s sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design calculation. The stated illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These assumptions do not establish that the trial was designed using that approach. The registry record does not report the trial’s sample-size justification. Planning sample sizes are illustrations of what might be needed under specified assumptions, not observed power and not evidence that a study did or did not have adequate power.
For continuous outcomes, a normal approximation can be used for planning or inference under suitable conditions. The registry record does not provide enough detail to determine whether assumptions about the outcome distribution were checked or how any departures were handled. Over-dispersion, in general, means that observed variation is larger than a model expects; if a model understates variability, uncertainty estimates may be too optimistic. No claim about over-dispersion or the distribution of this trial’s outcome can be made from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures and six analyses. It describes WOMAC LK3.1 pain change at 12 months as the primary outcome, with secondary outcomes involving pain, clinical success, function, and EQ-5D measures. The record does not report a statistical plan explaining how conclusions across outcomes were prioritized, whether formal multiplicity adjustment was used, or how any adjustment was performed. When multiple outcomes or analyses are examined, interpreting each result as though it were the only analysis can overstate the strength of evidence. The absence of a reported approach means the handling of multiplicity cannot be evaluated from the registry record.
For the primary outcome, the record identifies an intention-to-treat population and says that missing data were imputed. It does not report the imputation method, the assumptions about why data were missing, the amount of missing outcome data, or sensitivity analyses testing alternative assumptions. These details are important because imputed values are estimates, not observed participant scores, and the results can depend on how missingness is modeled.
The registry does not describe the specific analysis population for each secondary outcome, nor does it provide enough detail to assess whether all randomized participants were included in each analysis. It also does not report how the crossover design was represented in the analysis of the primary endpoint. No additional analysis populations or missing-data procedures should be inferred. The posted record therefore gives a broad statement about the primary population and imputation, but not the detail needed to assess robustness or reproduce the analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| nSTRIDE APS | 8 | 124 | 6.5% |
| Synvisc-One | 9 | 127 | 7.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| nSTRIDE APS | 0 of 124 |
| Synvisc-One | 0 of 127 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| nSTRIDE APS | 34 of 124 |
| Synvisc-One | 21 of 127 |
Most frequent serious adverse event terms
| Event term | Organ system | nSTRIDE APS | Synvisc-One |
|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 124 | 2 of 127 |
| Biliary colic | Hepatobiliary disorders | 0 of 124 | 1 of 127 |
| Medial Meniscus Lesion+Cartilage Lesion at Medial Femoral Condyle Left Knee | Musculoskeletal and connective tissue disorders | 1 of 124 | 0 of 127 |
| Uterine prolapse | Reproductive system and breast disorders | 1 of 124 | 0 of 127 |
| Wrist affected | Musculoskeletal and connective tissue disorders | 1 of 124 | 0 of 127 |
| Biceps tendon rupture right arm | Musculoskeletal and connective tissue disorders | 0 of 124 | 1 of 127 |
| Accute appendicitis | Gastrointestinal disorders | 1 of 124 | 0 of 127 |
| Infection index knee | Musculoskeletal and connective tissue disorders | 0 of 124 | 1 of 127 |
| Excessive swelling of Index Knee | Musculoskeletal and connective tissue disorders | 1 of 124 | 0 of 127 |
| Hypercalcemia | Blood and lymphatic system disorders | 0 of 124 | 1 of 127 |
Most frequent non-serious adverse event terms
| Event term | Organ system | nSTRIDE APS | Synvisc-One |
|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | 9 of 124 | 11 of 127 |
| Joint swelling | Musculoskeletal and connective tissue disorders | 10 of 124 | 4 of 127 |
| Injection site pain | Injury, poisoning and procedural complications | 8 of 124 | 4 of 127 |
| Joint stiffness | Musculoskeletal and connective tissue disorders | 4 of 124 | 0 of 127 |
| Injection site swelling | General disorders | 1 of 124 | 0 of 127 |
| Vessel puncture site bruise | General disorders | 1 of 124 | 0 of 127 |
| Arthritis bacterial | Infections and infestations | 0 of 124 | 1 of 127 |
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | 1 of 124 | 0 of 127 |
| Venipuncture | Surgical and medical procedures | 0 of 124 | 1 of 127 |
Serious events with the highest arm-level rate: arthralgia (1.6%), medial meniscus lesion+cartilage lesion at medial femoral condyle left knee (0.8%), uterine prolapse (0.8%), wrist affected (0.8%), accute appendicitis (0.8%).
The registry lists 124 participants at risk in the nSTRIDE APS group, with 8 affected by serious adverse events and 34 affected by other adverse events. In the Synvisc-One group, 127 participants were at risk, with 9 affected by serious adverse events and 21 affected by other adverse events. The record reports 0 deaths in each group. These are counts of participants listed as affected, not estimates of a comparative safety effect. The groups have different numbers at risk, and no adjusted comparison or uncertainty interval is reported.
The registry also lists serious adverse-event terms and percentages: Arthralgia, 1.6%; Medial Meniscus Lesion+Cartilage Lesion at Medial Femoral Condyle Left Knee, 0.8%; Uterine prolapse, 0.8%; Wrist affected, 0.8%; Accute appendicitis, 0.8%; and Excessive swelling of Index Knee, 0.8%. These entries describe reported terms and percentages in the record. They do not, by themselves, establish that an event was caused by a treatment. The record does not provide enough detail to assess event timing, relatedness, duration, or the basis for attributing an event to either treatment.
Serious and other adverse-event summaries should be interpreted as descriptive safety information. They do not establish that one treatment is safer than the other, particularly without a defined comparative analysis and precision estimates.
12. What the Result Does, and Does Not, Mean
The registry record establishes that NCT03182374 was a randomized, crossover study comparing nSTRIDE APS with Synvisc-One in knee osteoarthritis. It identifies a primary outcome based on change in WOMAC pain score from baseline to 12 months, and it describes the general study population and interventions. It also reports safety counts for the listed groups. These registry entries help explain what the study was designed to examine and what some of its recorded outcomes represent.
The record does not report the numerical primary outcome results. No arm-specific mean changes, standard deviations, between-treatment estimate, confidence interval, or p-value for the primary outcome are reported. As a result, the direction, magnitude, and precision of the primary comparison cannot be determined from the registry record. The endpoint definition is not a substitute for an outcome estimate, and the study design alone does not show what the results were.
The safety counts provide a descriptive account of participants recorded as affected by serious or other adverse events. Without a comparative safety analysis, event-level context, and uncertainty estimates, these counts cannot establish a difference in risk or a causal relationship between an event and treatment. The reported zero deaths in each group is a registry count, not a complete characterization of safety.
Important analytical details are also absent, including the crossover sequences and statistical handling of phase effects, the imputation method, and a multiplicity strategy. These omissions limit assessment of how the analyses were conducted and how robust a reported result might be. The registry record states that the study is completed, but completion status does not supply the missing numerical primary results. The sound interpretation is therefore limited: the study question and some design and safety details are described, while the principal treatment-effect estimate and its uncertainty are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable for its crossover design and its continuous patient-reported primary outcome. A crossover study can make within-participant comparisons possible, but it also makes treatment order and period effects important to analysis. If an earlier treatment influences later measurements, the contrast may be difficult to interpret without an appropriate design and analysis. Because the registry record does not describe treatment sequence, washout, or the analysis model, readers cannot assess how those issues were addressed.
The WOMAC pain score is defined in terms that make its direction clear: higher scores indicate worse pain, and the pain subscale ranges from 0-20. This helps readers understand what a reported change would mean. Yet an endpoint definition alone cannot show the size or precision of an observed difference. The primary numerical results are not reported in the registry record, so no treatment contrast can be evaluated against the scale or interpreted for importance.
The record also illustrates why analysis details matter beyond the headline design. It names an intention-to-treat population with imputation, but leaves the imputation method and assumptions unspecified. It lists multiple outcome measures and analyses without reporting how multiplicity was handled. It also contains differing descriptions of masking and enrollment: quadruple masking versus double-blind, and enrollment of 252 versus a planned total of 246 in the brief summary. The record does not explain these differences.
These gaps do not show that the trial’s analysis was inadequate; they limit what can be independently assessed from the registry record. Clear outcome estimates, uncertainty measures, and analysis details are essential for distinguishing a treatment contrast from the uncertainty around it and for judging how the study design shaped the result.
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 direct limitation for interpreting the primary endpoint is that the registry record does not report its numerical results. It defines a 12-month change in WOMAC pain score and identifies the analysis population, but gives no arm means, standard deviations, treatment contrast, confidence interval, or p-value. Thus, the primary treatment effect and its precision cannot be evaluated from this record.
Details needed to assess the crossover design are also not reported: treatment sequence, phase timing, washout arrangements, and the statistical method for handling period, sequence, or carryover effects. The record’s masking descriptions differ, with quadruple masking in the design information and double-blind wording in the brief summary. It does not explain who was masked or how masking was implemented. Enrollment is listed as 252, while the brief summary says a total of 246 patients will be enrolled; the relationship between those figures is not reported.
Missing-data methods are only described broadly. The record states that the primary analysis used an intention-to-treat population with imputations, but does not report the imputation approach, missingness assumptions, amount of missing data, or sensitivity analyses. It lists six outcome measures and six analyses without describing a multiplicity strategy. The protocol’s sample-size justification is not reported in the registry record; the stated sample-size assumptions describe a planning illustration rather than the trial’s own design calculation.
Safety information is presented as counts and selected event terms, without a comparative analysis or detail on event timing and relatedness. These limitations concern what can be assessed from the registry record and do not establish that the unreported methods or results were absent from other study materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: nSTRIDE APS Versus Hyaluronic Acid for Knee Osteoarthritis — NCT03182374.
- Registry record last updated 2024-09-19; status last verified 2024-04.
- Results first posted 2024-09-19.
- 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.
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18. Record Summary
NCT03182374 is listed as a completed, randomized, multicenter crossover study of nSTRIDE APS versus Synvisc-One for knee osteoarthritis. The registry record lists quadruple masking, while the brief summary calls the study double-blind. Enrollment is listed as 252; the brief summary states that 246 patients will be enrolled. The study start date is 2017-07-14, and primary completion is listed as 2019-09-30.
The primary outcome is change from baseline to 12 months in mean WOMAC LK3.1 pain score in both arms. The stated population is intention-to-treat, with imputations for missing data. Numerical primary results and key analysis details are not reported in the registry record. Serious adverse events affected 8 of 124 participants in the nSTRIDE APS group and 9 of 127 in the Synvisc-One group; other adverse events affected 34 and 21 participants, respectively. The record reports 0 deaths in each group.