Efficacy and Safety of HSK3486 Compared to Propofol for Adults Undergoing Elective Surgery With General Anesthesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of HSK3486 Compared to Propofol for Adults Undergoing Elective Surgery With General Anesthesia (NCT05478174), a randomized phase 3 study. The primary outcome is Success Rate of General Anesthesia Induction.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group Phase 3 study of HSK3486 versus propofol. Its official title characterizes the study as multicenter and double-blinded, while the masking field records quadruple masking. The record does not explain which people were included in the masking designation. The trial status is completed, and the registry lists Haisco-USA Pharmaceuticals, Inc. as sponsor.

The record gives an enrollment of 400. The primary outcome results list 255 participants in the HSK3486 group and 128 in the propofol group. These outcome denominators should be read as posted for that endpoint; the record does not explain the relationship between the enrollment figure and the endpoint-specific denominators. The adverse-event results use a different propofol denominator, which is discussed with the safety data.

The study began on 2022-07-26, and primary completion is recorded as 2023-11-07. The registry describes the study purpose as evaluating the efficacy and safety of HSK3486 injectable emulsion for induction of general anesthesia in adults undergoing elective surgery. Further information about sites, the randomization procedure, stratification, or the allocation sequence is 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

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 Success Rate of General Anesthesia Induction, measured over From the time of study drug administration to desired depth of anesthesia to MOAA/S≤1 ( up to 5 minutes).

The primary endpoint counts participants who achieved successful induction of general anesthesia. Success required reaching the stated depth of anesthesia, MOAA/S ≤1, after study-drug administration and requiring one or less top-up doses without rescue drugs. The registry timeframe runs from administration until the desired depth was reached, up to 5 minutes.

This is a binary outcome: each participant either met the composite success definition or did not. Combining the depth-of-anesthesia criterion with limits on top-up dosing and rescue-drug use makes the endpoint a measure of induction success under the trial’s stated conditions, rather than a measure of just reaching a sedation score. The record does not provide separate primary results for each component of the composite.

For a non-inferiority question, the key issue is whether the treatment difference is sufficiently small relative to a prespecified margin. The registry record does not report that margin, so readers cannot independently assess the clinical threshold used for the sponsor’s non-inferiority conclusion from this record alone. The posted sponsor analysis and the unadjusted recalculation also differ; the sponsor’s analysis takes precedence for interpretation of the trial’s own primary result.

7. Results Posted in the Registry

• Propofol: 100.0% (128/128) versus 99.2% (253/255) on control; risk difference 0.8 percentage points (95% CI -0.3 to 1.9), risk ratio 1.01 (1.00–1.02); unadjusted two-proportion z-test p = 0.315.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Propofol: 41.4% (53/128) versus 34.5% (88/255) on control; risk difference 6.9 percentage points (95% CI -3.4 to 17.2), risk ratio 1.20 (0.92–1.57); unadjusted two-proportion z-test p = 0.187.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Propofol and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects With Any Injection-site Pain on Numeric Rating Scale ≥1

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Propofol: 45.3% (58/128) versus 16.5% (42/255) on control; risk difference 28.8 percentage points (95% CI 19.1 to 38.6), risk ratio 2.75 (1.97–3.85); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Propofol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary endpoints address different aspects of the induction experience: maintaining the desired depth of anesthesia without significant cardiac and respiratory depression, and injection-site pain. Together, these outcomes broaden the description beyond the primary induction-success definition. They should not be treated as interchangeable with the primary endpoint, because they represent different event definitions and timeframes.

The registry also reports sponsor analyses for these outcomes, but the secondary results have less inferential weight than the primary result when considered without a stated multiplicity plan. Testing several outcomes increases the chance that at least one result may appear notable by chance. The registry record does not report whether the analyses were adjusted for multiple comparisons, or whether the secondary outcomes were ranked in a prespecified testing sequence. Their p-values should therefore be read as unadjusted unless the record states otherwise.

The secondary summaries can help describe patterns across efficacy and tolerability-related measures, but they do not resolve the primary-analysis discrepancy or establish the non-inferiority margin. The secondary endpoint concerning maintenance of anesthesia is related to the overall conduct of induction, yet it is not the same as the primary composite success outcome. Injection-site pain is a distinct reported outcome and should be interpreted on its own definition rather than as confirmation of the primary endpoint.

Planning illustrations based on observed secondary effects are hypothetical. They show how sample-size requirements would vary under stated planning assumptions and different fractions of an observed effect; they are not observed power, nor do they show what the original trial was designed to detect. The trial’s own sample-size assumptions are not reported in the registry record. Accordingly, the secondary endpoints add context, but their unadjusted results should remain supportive and exploratory in interpretation rather than carrying the same weight as the designated primary analysis.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression
• Percentage of Subjects With Any Injection-site Pain on Numeric Rating Scale ≥1

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary, so the basic descriptive quantities are counts of participants meeting the success definition and the corresponding endpoint denominators. A risk difference expresses the difference between the two groups’ event proportions. It is an absolute contrast, unlike a risk ratio, which compares proportions as a relative quantity. General statistical interpretation: an estimate near zero indicates little observed absolute separation in the sample, but its uncertainty and the prespecified decision rule are also important.

What does the unadjusted recalculation represent?

The recalculation uses the posted summary counts without adjustment. Its estimate is 0.008, with an interval from -0.003 to 0.019 and an unadjusted p-value of 0.315. The calculation is a simple check based on the outcome summaries, not a reconstruction of the sponsor’s full analysis. It does not account for information or modeling choices that may have been used in that analysis, and the registry record does not describe such details.

A confidence interval describes a range of values compatible with the data and the method under its assumptions. It is not a range containing a known fixed proportion of future study results, nor does it show the probability that a particular treatment effect is true. When an interval includes zero, the summary alone does not establish a directional difference under a conventional two-sided test. For non-inferiority, however, the relevant decision is based on whether the interval satisfies the prespecified margin, not simply whether it includes zero.

How does non-inferiority testing differ?

In general, a non-inferiority analysis asks whether an intervention is not worse than a comparator by more than a defined, prespecified amount. That amount is the non-inferiority margin. The margin is essential to interpret a non-inferiority result because it sets the boundary for an acceptable difference. It is not reported in the registry record. The sponsor’s reported primary analysis uses the Farrington-Manning method, gives a 95% confidence interval from -0.041 to 0.025, and reports p < 0.001 for non-inferiority. Without the margin and further analysis details, the registry record does not allow an independent check of the decision threshold.

The sponsor’s result and the unadjusted recalculation are not interchangeable. The discrepancy flag indicates that the posted sponsor analysis differs from the simple recalculation. The record does not explain whether the difference reflects analysis populations, missing data, model choices, or another reason; each is not reported in the registry record. Accordingly, the formal sponsor result is the relevant reported trial analysis, while the recalculation is best read as a separate, unadjusted description of the summary counts.

Why can over-dispersion matter?

General explanation: for count outcomes, a model may assume a particular relationship between the average and variability. If the observed variability is greater than that assumption allows, the data are over-dispersed. Standard errors and confidence intervals can then be too narrow if the extra variability is ignored. This primary endpoint is reported as a binary participant count, not as a rate of events over person-time, and the registry record does not report an over-dispersion analysis for it. Over-dispersion should not be presumed to be a feature of this result.

What do the sample-size illustrations mean?

The secondary-outcome planning illustrations are calculated from observed effects, with two-sided significance level 0.05, equal allocation, and a normal approximation. They show participants per arm for 80% or 90% power when planning around 100%, 75%, or 50% of the observed effect. Such illustrations are hypothetical planning aids, not observed power and not evidence that the trial was designed around those effects. The record does not report the trial’s own sample-size justification or assumptions, so the illustrations should not be mistaken for the design rationale.

The registry record does not report a full statistical analysis plan, analysis populations, missing-data procedures, interim analyses, or multiplicity adjustment. Those details would help readers understand how endpoints and participants were handled, but their absence does not authorize assumptions about the methods used. The reported quantities should therefore be interpreted at the level of detail available in the registry record.

11. Confidence Intervals and Precision

The unadjusted primary risk-difference estimate is 0.008, and its interval extends from -0.003 to 0.019. The interval spans zero, so the recalculated summary is compatible with small differences in either direction under the calculation’s assumptions. Its width also indicates uncertainty around the estimate; the point estimate alone should not be treated as a precise measure of the underlying contrast.

The sponsor’s reported primary 95% confidence interval is -0.041 to 0.025 around a risk difference of -0.008. This is a different analysis from the unadjusted recalculation, and the interval is not interchangeable with the recalculated interval. The discrepancy is flagged in the registry record, which does not provide enough information to reconcile the two. The sponsor’s own analysis takes precedence for the trial’s reported non-inferiority inference.

For non-inferiority, precision must be considered against the margin chosen before analysis. The registry record does not report that margin. As a result, readers cannot judge from the interval alone how close its bounds are to the non-inferiority boundary. A p-value below a threshold does not convey the size or practical importance of the effect, and it cannot substitute for the missing margin.

General explanation: intervals quantify uncertainty under a specified method and its assumptions. They do not address potential bias from missing data, selection of an analysis population, or other design and conduct issues. Those matters are not reported in the registry record, limiting what can be concluded about precision beyond the uncertainty represented by the posted intervals.

12. Analyses Reported by the Sponsor

The sponsor’s primary result is a Farrington-Manning non-inferiority analysis: risk difference -0.008, 95% confidence interval -0.041 to 0.025, and p < 0.001. The registry classifies it as a non-inferiority analysis. The sponsor’s result is the trial’s own reported inferential analysis and takes precedence over the unadjusted recalculation when describing the primary finding.

The recalculation from the posted summary counts gives an estimate of 0.008, an interval from -0.003 to 0.019, and an unadjusted p-value of 0.315. Its estimate has the opposite sign, consistent with reversing the order of the group contrast. The intervals and p-values differ as well, so the discrepancy is not explained simply by reversing the sign. The registry record does not report why the analyses differ.

The non-inferiority margin and detailed analysis-population and missing-data procedures are not reported in the registry record. Without the margin, the sponsor’s p-value cannot be evaluated against the decision boundary from the registry information alone. The recalculation should be treated as an unadjusted check of the posted counts, not as a replacement for the sponsor’s analysis or as evidence that the two analyses agree.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and two secondary outcomes. It does not report a multiplicity adjustment, a hierarchical testing procedure, or another strategy for controlling the chance of false-positive findings across outcomes. Those procedures are not reported in the registry record. Without them, secondary p-values are best understood as unadjusted analyses rather than as results protected by a stated family-wise testing plan.

Analysis populations are also not described. The record does not say whether the primary analysis used an intention-to-treat, per-protocol, modified intention-to-treat, or other population. This is particularly relevant to non-inferiority studies, for which population definitions and handling of protocol deviations can affect interpretation. These details are not reported in the registry record, so no specific population or analysis approach should be assumed.

Missing-data methods are not reported in the registry record. The posted primary results give outcome denominators for each arm, but the record does not explain whether any participants lacked endpoint data, how such cases were handled, or whether sensitivity analyses were conducted. The same limitation applies to the secondary outcomes. A posted denominator alone does not establish the missing-data method or show that data were complete.

The registry record does not report interim analyses, stopping rules, or a complete statistical analysis plan. It also does not report the non-inferiority margin or the rationale for the enrollment target. These omissions make it difficult to assess how the analysis was planned in advance and how robust the reported inference is to alternative assumptions. The discrepancy between the sponsor’s primary result and the unadjusted recalculation is flagged, but its cause is not reported in the registry record.

These omissions do not invalidate the posted results, but they limit independent assessment. The sponsor’s formal primary analysis remains the reported analysis for the non-inferiority question, while the secondary findings require caution because no multiplicity procedure is reported. Neither missing-data handling nor the analysis population can be inferred from the outcome counts.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: post-procedural hemorrhage (0.8%), ischemic stroke (0.8%), hiatus hernia (0.8%), hypotension (0.4%), confusional state (0.4%).

The serious adverse event summary reports 6 affected participants among 255 at risk in the HSK3486 group and 2 among 129 at risk in the propofol group. No deaths are listed in either group. The adverse-event denominators differ from the propofol denominator in the primary endpoint results; the registry record does not explain the difference. Safety counts should therefore be read using their own posted denominators, not substituted with the efficacy denominators.

The record lists post-procedural hemorrhage, ischemic stroke, and hiatus hernia at 0.8% each, and hypotension, confusional state, and urinary tract infection at 0.4% each among the top serious terms. Such listings identify reported event terms; they do not establish that study treatment caused an event. The registry summary does not provide enough detail to assess event timing, severity beyond the serious designation, attribution, or comparative risk. These counts describe reported safety data and do not support a causal conclusion on their own.

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

The registry record describes a randomized comparison of HSK3486 and propofol for induction of general anesthesia in adults undergoing elective surgery. Its primary endpoint is a defined induction-success composite, and the sponsor reports a non-inferiority analysis. The posted result should be understood as an analysis of that specific endpoint under the trial’s stated conditions, rather than as a broad measure of all aspects of anesthesia or surgery.

The primary result does not establish that the treatments are identical. Non-inferiority asks whether a difference falls within a prespecified boundary, and the boundary is not reported in the registry record. The sponsor’s own analysis takes precedence over the unadjusted recalculation, but the missing margin and analysis details prevent independent assessment of the decision threshold from the registry record alone.

Nor do the results establish an effect on outcomes not reported in the record. The endpoint focuses on reaching a target depth and limiting top-up doses and rescue drugs. It does not, by itself, summarize all subsequent anesthetic management, recovery, or surgical outcomes. The secondary endpoints and adverse-event summaries add information on selected outcomes, but they have their own definitions, denominators, and limitations.

The findings also do not resolve how the results apply outside the studied adults undergoing elective surgery with general anesthesia. Further information about participant characteristics, sites, analysis populations, missing data, and the non-inferiority margin is not reported in the registry record. Statistical significance, whether from a p-value or a confidence interval, does not by itself determine clinical importance or generalizability.

In short, the record presents a sponsor-reported non-inferiority result alongside an unadjusted recalculation that differs. The sponsor result is the relevant reported trial analysis, while its interpretation is constrained by the absent margin and by incomplete methods information. The posted counts and intervals describe the trial record; they are not a general guarantee about outcomes for every patient or setting.

16. Why This Trial Matters Statistically

This trial illustrates why the direction and definition of a treatment contrast matter. The unadjusted recalculation and sponsor analysis report risk differences with opposite signs, and their intervals and p-values differ. A reader who focuses only on the point estimate could miss that the estimates are from different analyses. The registry flags the discrepancy, making it important to distinguish the sponsor’s formal primary inference from a simple recalculation of posted counts.

It also highlights the special role of the non-inferiority margin. Unlike a basic test of whether a difference is zero, non-inferiority depends on a prespecified boundary for an acceptable loss. The sponsor reports a non-inferiority analysis, but the margin is not reported in the registry record. The statistical conclusion therefore cannot be independently checked against its defining threshold using the registry information alone.

The endpoint definition is another key statistical issue. Success requires both a target depth of anesthesia and limits on top-up dosing and rescue drugs. That composite definition creates a clinically interpretable summary of induction, but the registry does not report component-specific primary results. A single overall count cannot show which part of the definition accounts for unsuccessful outcomes.

Finally, the record distinguishes a designated primary outcome from secondary outcomes, while not reporting a multiplicity strategy or full analysis plan. This matters because multiple unadjusted comparisons should not be read as though each had the same confirmatory status. Together, these features make the trial a useful example of how study question, estimand, margin, analysis method, and reporting completeness all shape statistical interpretation.

17. 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 record does not report the non-inferiority margin, despite classifying the sponsor’s primary analysis as non-inferiority. Without that boundary, the reported interval cannot be assessed against the trial’s decision criterion. The discrepancy between the sponsor’s analysis and the simple unadjusted recalculation is also not explained, limiting independent reconciliation of the primary result.

Further analysis details are not reported in the registry record, including the primary analysis population, missing-data handling, sensitivity analyses, and a complete statistical analysis plan. The record also does not state whether multiplicity was controlled for the secondary outcomes. These gaps limit assessment of prespecification and robustness, and the secondary results should be interpreted accordingly.

The registry provides overall primary endpoint counts but no component-level results for the composite definition. It therefore does not show separately whether participants failed to reach MOAA/S ≤1, required additional top-up dosing beyond the allowed amount, or used rescue drugs. Participant characteristics and detailed site information are not reported in the registry record, restricting assessment of how representative the enrolled population may be.

The safety summary lists serious events and selected terms but does not provide event-level timing, attribution, or other detail needed to assess causal relationships. The adverse-event propofol denominator also differs from the primary outcome denominator, and the reason is not reported in the registry record. These are limitations of the information available in the record, not proof that the underlying trial did not collect further data.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety of HSK3486 Compared to Propofol for Adults Undergoing Elective Surgery With General Anesthesia — NCT05478174.
• Registry record last updated 2025-10-10; status last verified 2025-09.
• Results first posted 2024-10-29.
• 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.

21. Record Summary

The registry records a completed, randomized, parallel-group Phase 3 study comparing HSK3486 with propofol for induction of general anesthesia in adults undergoing elective surgery. Enrollment is listed as 400. The primary endpoint counts successful induction, defined by reaching MOAA/S ≤1 within the stated timeframe and requiring one or less top-up doses without rescue drugs.

The sponsor reports a Farrington-Manning non-inferiority analysis, while the registry flags a discrepancy with an unadjusted recalculation from posted counts. The sponsor analysis takes precedence for the trial’s reported primary inference. The non-inferiority margin, analysis populations, missing-data methods, and multiplicity strategy are not reported in the registry record, limiting independent assessment of the result and secondary findings.