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 The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK) (NCT04573881), a na na study. The primary outcome is Primary Efficacy: Technical Success.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04573881 |
| Phase | NA |
| Condition | Liver Neoplasms, Hepatocellular Carcinoma, Liver Metastases |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | HistoSonics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with primary or metastatic tumors located in the liver. The registry lists liver neoplasms, hepatocellular carcinoma and liver metastases as conditions.
Intervention
Treatment with the HistoSonics System, a device.
Comparator
There is no comparator group. The trial is described as single-arm and non-randomized.
Primary question
Does treatment achieve technical success, defined by treatment dimensions that cover the targeted tumor on CT or MR imaging? The trial also evaluates efficacy and safety, with technique efficacy and all adverse events listed as secondary outcomes.
The clinical question is about whether treatment reaches the intended imaging-defined coverage, rather than whether outcomes differ from another treatment. Technical success is assessed within 36 hours after the index procedure and is adjudicated by a core laboratory. Four tumors had insufficient imaging data for that laboratory to evaluate technical success.
The registry states that the trial’s objective is to evaluate the efficacy and safety of the device for primary or metastatic liver tumors. It does not report a comparative question, a control treatment, or random allocation. Consequently, the record can describe observations after treatment but cannot by itself establish how those observations compare with outcomes under another approach.
3. Trial Design
This is a prospective, single-group, non-randomized trial of the HistoSonics System for primary or metastatic liver tumors. The registry lists an enrollment of 24 and identifies the device as the intervention. No separate control arm is described. Allocation is listed as NA, and masking is listed as none. The phase is listed as NA.
The study began on 2021-06-04, and the primary completion date is 2022-09-29. Its current registry status is active, not recruiting. These registry fields describe study conduct and status; they do not establish that all analyses or follow-up are complete.
The primary outcome is technical success, expressed as a percentage of tumors. It is assessed within 36 hours after the index procedure. The definition requires the treatment volume or dimensions to be at least as large as the targeted tumor, with complete tumor coverage, as evaluated using CT or MR imaging and adjudicated by a core laboratory. The registry notes that imaging was insufficient to evaluate technical success for four tumors.
Secondary outcomes are technique efficacy and all adverse events. The record identifies four outcome measures but lists zero analyses. The primary endpoint’s numerical estimate and confidence interval are not reported in the registry record. Numerical results for the secondary efficacy outcome are also not reported in the registry record.
Because there is no randomized comparator, the design is descriptive rather than a direct test of comparative effectiveness. A single-group trial can characterize observed technical and safety outcomes in the studied participants, but it cannot separate the intervention’s effects from other influences as a controlled comparison would. The registry record does not report details of the protocol, sample-size justification, interim analyses, or a statistical analysis plan.
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
| Stage | HistoSonics System |
|---|---|
| STARTED | 24 |
| COMPLETED | 0 |
| NOT COMPLETED | 24 |
Reasons for not completing this period:
| Reason | HistoSonics System |
|---|---|
| Participant in active follow-up at 30 days | 24 |
Analysis population for the primary outcome, as defined in the registry: Four tumors had insufficient imaging data for the core laboratory to evaluate technical success.
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 | HistoSonics System |
|---|---|---|
| Participants analysed | 24 | |
| Age, Continuous | years | 62.9 (SD 10.0) |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 10 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 20 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race/Ethnicity, Customized: White | Participants | 23 |
| Race/Ethnicity, Customized: Other | Participants | 1 |
| Type of tumor: Hepatocellular carcinoma | Participants | 7 |
| Type of tumor: Liver metastasis | Participants | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Primary Efficacy: Technical Success, measured over ≤36 hours post-index procedure.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of tumors |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is technical success, reported as a percentage of tumors. The registry defines success by imaging evidence that the treatment volume or dimensions are at least as large as the targeted tumor and provide complete tumor coverage. CT or MR imaging is used, and a core laboratory adjudicates the assessment. The evaluation is scheduled within 36 hours after the index procedure.
This endpoint focuses on whether the intended treatment coverage was achieved, rather than on a later clinical outcome. As a general statistical principle, an imaging-based technical endpoint can provide a structured way to assess whether a procedure reached its immediate target. It does not, by itself, establish longer-term tumor control or a patient-level clinical benefit.
The measure is defined per tumor, while enrollment is recorded for the trial. The record does not report the number of tumors with evaluable imaging or the numerical percentage meeting the technical-success definition. It does state that four tumors had insufficient imaging data for core-laboratory assessment. The planned 95% confidence interval is named as the measure of dispersion, but its numerical limits are not reported in the registry record.
Without the endpoint estimate and its interval, readers cannot assess the observed level of technical success or its precision from the registry record. The imaging definition and timing clarify what the endpoint was intended to measure, but they do not substitute for the missing outcome result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a prospective evaluation of a device in a single group, with technical success as the primary endpoint. The endpoint is clearly defined in terms of tumor coverage on CT or MR imaging, with core-laboratory adjudication within 36 hours after the index procedure. However, the numerical technical-success result and its planned 95% confidence interval are not reported in the registry record. Therefore, the primary endpoint cannot be quantitatively interpreted from this record.
The record says imaging was insufficient for technical-success evaluation for four tumors. This is important because an endpoint expressed as a percentage of tumors depends on which tumors can be assessed and how missing assessments are handled. The record does not state the evaluable denominator, whether unavailable imaging was excluded from the calculation, or whether any alternative missing-data approach was used. These details are not reported in the registry record.
Technique efficacy and all adverse events are listed as secondary outcomes, but numerical efficacy results are not reported in the registry record. The adverse-event information records serious adverse events affecting 7 participants among 24 at risk, and other adverse events affecting 14 participants among 24 at risk. The record lists 0 deaths. These are descriptive counts; they are not evidence of a comparative treatment effect, and the single-group design offers no control group for comparison.
Six serious adverse-event terms are each listed at 4.2%: hepatic failure, postoperative thrombosis, procedural pain, splenic haematoma, melaena/melena and chest pain. The registry record does not provide further information about event timing, severity grading, recurrence, duration, or attribution. The listed percentage should therefore be read as a registry-reported value for each term, not as an independently interpretable risk estimate without its counting and denominator details.
The design does not use random allocation and does not include a like-for-like control group. Observed outcomes can describe what was recorded in this treated group, but they cannot show how outcomes would have differed under an alternative treatment or no treatment. The record does not report the statistical analysis plan, planned handling of multiple outcomes, or details of the analysis population.
Planning illustrations based on an observed effect are hypothetical calculations, not evidence of observed power and not a substitute for the trial’s own design justification. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. Those assumptions do not turn this single-group trial into a randomized comparison, and the sample-size justification for the trial itself is not reported in the registry record.
9. Statistical Methods Explained
The registry identifies the primary outcome as a percentage of tumors and names a 95% confidence interval as its dispersion measure. A percentage describes the share of assessed units meeting a definition. Here, the unit named is the tumor, not the participant. The registry does not report the numerical percentage, the confidence limits, or the evaluable denominator, so the precision of the primary estimate cannot be examined from the record.
In general, a confidence interval gives a range of values compatible with an estimate under the statistical method used. Its width reflects uncertainty: wider intervals indicate less precision, while narrower intervals indicate greater precision. A confidence interval is not a guarantee that the true value lies within its limits, and it does not by itself show whether a result is clinically meaningful. The registry specifies the intended confidence level but gives no numerical interval. The method used to calculate it is not reported in the registry record.
The endpoint depends on imaging and core-laboratory review. Core-laboratory adjudication can apply a consistent assessment process, but interpretation still depends on image availability and the endpoint rules. The record notes insufficient imaging for four tumors. It does not report whether those tumors were excluded from the primary calculation, counted as failures, or handled in another way. That uncertainty matters because different missing-data rules can change the estimate and its precision.
The distinction between tumors and participants is relevant to statistical interpretation. A percentage per tumor is not automatically equivalent to a percentage per participant. The record does not report how many tumors were assessed overall or whether participants contributed more than one tumor to the endpoint. If multiple tumors from a participant are included, their outcomes may be related. As a general statistical principle, analyses that treat related observations as independent can understate uncertainty; appropriate methods may account for clustering. The analysis method and the handling of any such relationship are not reported in the registry record.
What does the single-group design permit?
A single-group design describes outcomes among people who received the intervention. It can provide a record of technical outcomes and adverse events in the study group. Without a concurrent control group, it cannot estimate a direct treatment contrast. Random allocation is not used, and the registry lists no comparator. Differences that might arise in a controlled comparison cannot be separated from changes over time, participant characteristics, or other influences using this design alone. The registry’s allocation field is listed as NA, and the study is described as non-randomized.
The posted planning assumptions refer to two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power. They do not report the power actually achieved, and they should not be interpreted as the trial’s sample-size justification. The sample-size justification and statistical plan are not reported in the registry record. A two-arm planning framework also does not change the design of this single-group trial.
How should event counts be interpreted?
The safety record distinguishes serious adverse events from other adverse events and records participants at risk and participants affected. These counts describe the registry’s safety reporting; they do not establish that an event was caused by the device. General interpretation of adverse-event data depends on definitions, surveillance duration, ascertainment, and attribution. Further detail on these aspects is not reported in the registry record.
The registry also lists serious-event terms with percentages. Without the term-level counts and explanation of the denominator or counting convention, those percentages cannot be reconstructed or compared reliably with the participant-level affected counts. No additional rate, risk difference, or relative measure should be inferred from the listed values.
What is known about multiplicity and analysis?
The record names a primary outcome and secondary outcomes, but does not report how statistical testing across these outcomes was controlled or interpreted. In general, testing several outcomes can increase the chance of observing a nominally unusual result by chance. Methods such as hierarchical testing or adjusted thresholds can address this issue, but a particular approach cannot be attributed to this trial because the statistical plan is not reported in the registry record. The registry lists zero analyses, and it does not provide numerical outcome analyses for the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry names technical success as the primary outcome and lists technique efficacy and all adverse events as secondary outcomes. It does not report a multiplicity strategy, such as a testing hierarchy or adjustment for multiple statistical comparisons. In general, when several outcomes are tested, the chance of at least one apparently unusual finding can increase. Whether that concern applied to the trial’s analysis, and how it was handled, is not reported in the registry record.
The registry identifies four outcome measures and zero analyses. The primary outcome’s numerical estimate and 95% confidence interval are not reported in the registry record. Numerical secondary efficacy results are also not reported. The record’s adverse-event counts and terms are descriptive entries, rather than a full account of an inferential analysis.
Missing imaging is specifically noted: four tumors had insufficient data for core-laboratory assessment of technical success. The record does not report the primary endpoint’s evaluable denominator, the treatment of those unavailable assessments in the estimate, or any sensitivity analysis. These omissions prevent readers from determining how missing imaging influenced the reported endpoint, and no numerical estimate is available to evaluate in any case.
The analysis populations are not described in detail. The record does not say whether the endpoint analysis used all enrolled participants, only participants with evaluable imaging, or another defined population. The statistical analysis plan and the handling of protocol deviations are not reported in the registry record. These gaps limit reproducibility and make it difficult to assess whether the endpoint definition, analysis set and missing-data handling align.
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 |
|---|---|---|---|
| HistoSonics System | 7 | 24 | 29.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| HistoSonics System | 0 of 24 |
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 |
|---|---|
| HistoSonics System | 14 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | HistoSonics System |
|---|---|---|
| Hepatic failure | Hepatobiliary disorders | 1 of 24 |
| Postoperative thrombosis | Injury, poisoning and procedural complications | 1 of 24 |
| Procedural pain | Injury, poisoning and procedural complications | 1 of 24 |
| Splenic haematoma | Blood and lymphatic system disorders | 1 of 24 |
| Melaena/Melena | Gastrointestinal disorders | 1 of 24 |
| Chest pain | General disorders | 1 of 24 |
| Sepsis | Infections and infestations | 1 of 24 |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HistoSonics System |
|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | 6 of 24 |
| Pyrexia | General disorders | 4 of 24 |
| Abdominal pain | Gastrointestinal disorders | 3 of 24 |
| Anaemia/Anemia | Blood and lymphatic system disorders | 2 of 24 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 24 |
| Constipation | Gastrointestinal disorders | 1 of 24 |
| Asthenia | General disorders | 1 of 24 |
| Discomfort | General disorders | 1 of 24 |
| Localized oedema | General disorders | 1 of 24 |
| Procedural nausea | Injury, poisoning and procedural complications | 1 of 24 |
Serious events with the highest arm-level rate: hepatic failure (4.2%), postoperative thrombosis (4.2%), procedural pain (4.2%), splenic haematoma (4.2%), melaena/melena (4.2%).
The safety record lists 24 participants at risk for serious adverse events, with serious events affecting 7. It also lists 24 at risk for other adverse events, with other events affecting 14. The registry lists 0 deaths. These are descriptive counts from the single-group study, not comparisons with another group.
The serious-event terms listed are hepatic failure, postoperative thrombosis, procedural pain, splenic haematoma, melaena/melena and chest pain. Each is shown at 4.2%. The record does not provide further term-level counts or explain the denominator and counting convention for these percentages. They should be read as registry-reported percentages, not recalculated into a rate or used to infer how events were distributed among participants.
Adverse events recorded during a trial are not necessarily caused by the intervention. The record does not report event attribution, timing, duration, recurrence, or severity grading. It also does not provide enough detail to judge the intensity or completeness of safety surveillance. As a result, the counts describe what the registry records, while causal interpretation and comparison with other settings remain unsupported.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the trial was designed to evaluate technical success and safety after use of the HistoSonics System for primary or metastatic liver tumors. It defines technical success using imaging-based tumor coverage and identifies the timing and core-laboratory assessment. It also records adverse-event counts and a list of serious-event terms.
It does not report the numerical primary endpoint result or its 95% confidence interval. Therefore, the record does not support a quantitative statement about the observed percentage of tumors meeting the technical-success definition, or how precise that percentage was. The note that four tumors lacked sufficient imaging for core-laboratory assessment further highlights an unresolved missing-data issue; the registry does not describe how those assessments were treated.
The safety counts indicate what was recorded among participants at risk, including serious adverse events affecting 7 participants and other adverse events affecting 14 participants; the record lists 0 deaths. These are not comparative estimates and do not establish whether events were caused by treatment. The term-level percentages are listed, but supporting counting details are not reported.
The design also limits what can be concluded. A non-randomized, single-group evaluation has no comparator with which to estimate differences in outcomes. It can describe the study group, but cannot show what would have happened to comparable participants under a different approach. The registry record does not report a statistical analysis plan, sample-size justification, or a detailed account of analysis populations and missing-data handling.
Accordingly, the record documents the trial’s question, design and some safety observations, but it does not provide enough outcome information for a statistical assessment of the primary efficacy endpoint. It should not be read as evidence for a treatment effect or as a comparison against another therapy.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition and an endpoint result are both essential. Technical success is specified in concrete imaging terms, with a stated assessment window and core-laboratory adjudication. That makes the intended measure understandable. Yet, without its numerical estimate, confidence interval and evaluable denominator, readers cannot assess the observed result or its precision.
It also highlights the difference between tumor-level and participant-level outcomes. The primary endpoint is expressed as a percentage of tumors, while enrollment and safety counts are presented for participants. Those units answer different questions. Where more than one tumor may contribute to a participant-level record, dependence between observations can matter statistically; whether that applies and how it was handled are not reported in the registry record.
The note about insufficient imaging makes missingness part of the endpoint interpretation, not merely a reporting detail. The effect of unavailable assessments depends on how the analysis handles them. Because the record does not state the denominator or the missing-data rule, readers cannot evaluate the potential influence on the technical-success estimate.
The single-group design is another important statistical feature. It can describe recorded outcomes, including adverse events, but cannot supply a randomized treatment contrast. This distinction helps prevent descriptive counts from being interpreted as proof of comparative benefit or harm. Finally, the safety record demonstrates that event counts and term-level percentages need clear denominators, definitions and attribution information to support interpretation. Those details are not reported in the registry record.
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 interpretation is that the primary endpoint’s numerical result and confidence interval are not reported in the registry record. Although technical success is defined, the result cannot be evaluated for magnitude or precision. The record also notes insufficient imaging for four tumors and does not describe how those cases were handled or give the endpoint’s evaluable denominator.
The study is single-group and non-randomized, with no comparator. Its observations cannot estimate a controlled difference between treatments. The record does not report details of participant selection, baseline characteristics, follow-up beyond the stated primary endpoint timing, or the treatment of protocol deviations.
The registry lists technique efficacy and all adverse events as secondary outcomes, but does not provide numerical efficacy results. Safety reporting lacks details on event timing, duration, severity grading, attribution and surveillance. The serious-event percentages are listed without term-level counts or a clear counting convention in the record.
Statistical limitations include the absence of a reported analysis plan, multiplicity approach, analysis populations, and missing-data methods. The record does not report how tumor-level observations were handled if they were related within participants. It also does not report the trial’s sample-size justification or interim-analysis plans. These gaps constrain independent evaluation of the analysis and interpretation of the recorded findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK) — NCT04573881.
- Registry record last updated 2026-01-12; status last verified 2025-12.
- Results first posted 2024-08-19.
- 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
The registry describes NCT04573881, a prospective, non-randomized, single-group study of the HistoSonics System for primary or metastatic liver tumors. Enrollment is listed as 24. The study began on 2021-06-04, its primary completion date is 2022-09-29, and its status is active, not recruiting.
The primary outcome is technical success, defined by imaging-confirmed complete coverage of the targeted tumor, assessed within 36 hours after the index procedure and adjudicated by a core laboratory. Four tumors had insufficient imaging for assessment. The numerical primary result and confidence interval are not reported in the registry record.
Secondary outcomes are technique efficacy and all adverse events. The record lists serious adverse events affecting 7 participants, other adverse events affecting 14 participants, and 0 deaths. It does not provide a randomized comparison or enough analysis detail to support comparative conclusions.