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 Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects (NCT03393000), a randomized phase 3 study. The primary outcome is Overall Survival (OS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03393000 |
| Phase | Phase 3 |
| Condition | Glioblastoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Diffusion Pharmaceuticals Inc |
| Results posted | Yes |
2. Clinical Question
Population
People with newly diagnosed glioblastoma who were biopsy-only subjects. The registry record reports enrollment of 19 participants. Further eligibility criteria and a fuller description of the population are not reported in the registry record.
Intervention
Trans Sodium Crocetinate (TSC) given with standard of care. The standard-of-care regimen is radiation therapy and temozolomide, followed by a rest period and post-radiation temozolomide cycles.
Comparator
Standard of care without TSC, consisting of radiation therapy and temozolomide, followed by a rest period and post-radiation temozolomide cycles.
Primary question
Does adding TSC to standard care change overall survival, measured from randomization until death from any cause? The registry record does not report a comparative primary-outcome result.
The clinical question is framed as a comparison between two treatment strategies, not as an evaluation of TSC in isolation. Both groups were intended to receive the same standard-care backbone; the planned difference was the addition of TSC in the intervention group. The study is described as randomized, controlled, open-label, and parallel-group.
Overall survival is the primary outcome named in the registry record. It is a time-to-event measure: the event is death from any cause, and the stated origin for measuring time is randomization. The record describes follow-up for 24 months. It does not give an estimate of the difference between groups, an estimate for either group’s median survival, or a confidence interval for a comparative effect. It also does not report a primary-outcome analysis. Consequently, the clinical question can be described, but the posted information does not answer it.
3. Trial Design
NCT03393000 is described as an open-label, randomized, controlled, phase 3 study with a parallel-group model. Participants were to be assigned at baseline to TSC plus standard care or standard care alone. The record lists Glioblastoma as the condition and gives the title as a safety and efficacy study in newly diagnosed glioblastoma biopsy-only subjects. Enrollment is recorded as 19.
The standard-care regimen is described as radiation therapy with temozolomide for 6 weeks, followed by a rest period, then post-radiation temozolomide. The brief summary describes 28 days of rest and six cycles of post-radiation treatment. The arm descriptions specify 4 weeks of rest and six 28-day cycles. Those descriptions identify the intended treatment sequence; they do not establish how much treatment each participant received or whether the regimens were completed.
Open-label means the registry does not describe masking of treatment assignment; masking is listed as none. The method used to generate the random allocation sequence, conceal assignment before enrollment, or manage departures from assigned treatment is not reported in the registry record. The record identifies Diffusion Pharmaceuticals Inc as the sponsor.
The study is marked terminated. The start date is 2018-01-16, and the primary completion date is 2020-11-06. The reason for termination and the timing or circumstances of the decision are not reported in the registry record. Although the study is described as phase 3, its recorded enrollment is 19, and the registry record does not contain a comparative overall-survival result. The designation and planned design should therefore be distinguished from the evidence available in the posted results.
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 | Trans Sodium Crocetinate Plus SOC |
|---|---|
| STARTED | 19 |
| COMPLETED | 5 |
| NOT COMPLETED | 14 |
Reasons for not completing this period:
| Reason | Trans Sodium Crocetinate Plus SOC |
|---|---|
| Death | 11 |
| Withdrawal by Subject | 2 |
| Physician Decision | 1 |
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 | Trans Sodium Crocetinate Plus SOC |
|---|---|---|
| Participants analysed | 19 | |
| Age, Continuous | years | 61 (22 to 70) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 10 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 14 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 17 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | Participants | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival (OS), measured over All subjects will be followed for 24 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is overall survival, expressed as a median in months. The registry defines overall survival as the time from randomization to death from any cause and states that all subjects will be followed for 24 months. The planned summary includes a 95% confidence interval.
As a general statistical concept, a time-to-event endpoint incorporates both whether an event occurs and how long it takes to occur. Overall survival uses death from any cause as the event, so it does not require deciding whether a death was caused by the cancer or treatment. A median survival time is the point at which the estimated survival distribution reaches its midpoint. A confidence interval describes uncertainty around an estimate; it is not a range containing a known individual participant’s survival time.
Overall survival is commonly used in clinical trials because the event is clearly defined and directly observable, whereas other outcomes may depend on assessments or rules for classifying disease status. That general rationale does not establish that the endpoint was fully observed or analyzed in this trial. The registry record does not report a median, confidence interval, group-specific survival estimate, or comparative effect. It also does not describe censoring rules, the analysis method, or how participants lost to follow-up were handled. The endpoint is specified, but its result cannot be evaluated from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies overall survival as the primary endpoint and defines it as time from randomization to death from any cause. It does not post an estimate of median overall survival, a confidence interval, a hazard ratio, or a statistical test comparing the treatment groups. The record also indicates that no analyses are listed and that the primary-outcome entry was skipped because fewer than two arms were present for that outcome. Accordingly, there is no posted comparative primary-outcome finding to interpret.
Enrollment was 19, and the study status is terminated. These registry entries describe the size and status of the trial, but they do not explain why enrollment ended or whether the planned follow-up was completed. The registry gives no termination reason. It also does not report how many participants were assigned to each group, how many contributed survival follow-up, how many were censored, or whether the planned 24-month follow-up was achieved.
The record’s safety information is separate from a comparative survival analysis. It lists a safety group titled Trans Sodium Crocetinate Plus SOC, with 19 participants at risk for serious adverse events and 11 affected, and 19 at risk for other adverse events and 19 affected. It also lists 14 deaths. These are descriptive safety counts in the registry entry; they do not supply a treatment-group comparison for overall survival or establish the timing or cause of deaths.
A confidence interval would ordinarily help readers assess the precision of an estimated survival quantity or treatment effect. No such interval is posted for the primary outcome, so the precision of a comparative estimate cannot be judged. Likewise, the absence of a reported p-value or hazard ratio is not evidence of equivalence, benefit, or harm. The available record simply does not provide those results.
Any numerical planning illustrations based on an observed effect require an effect estimate to serve as their input. Because no primary-outcome effect is reported, such illustrations should not be treated as evidence about the trial’s findings or as observed statistical power. They are planning calculations, not a substitute for the sponsor’s primary analysis. No sponsor-reported primary-outcome analysis is available in the registry record.
The main statistical conclusion is therefore about reporting, not treatment: the design posed a randomized comparison, but the posted record does not report the primary survival result needed to quantify that comparison. The safety figures can be described as recorded, with appropriate caution about their context, but they cannot fill that gap.
9. Statistical Methods Explained
The registry record describes a randomized, open-label, parallel-group phase 3 trial. The named primary outcome is a time-to-event measure, and the intended summary is median overall survival with a 95% confidence interval. The record does not describe the analysis used to produce those quantities, and no primary-outcome result is posted.
What does randomization contribute?
In general, randomization assigns participants to treatment strategies using a chance-based process. Its purpose is to make the groups comparable, on average, with respect to both known and unknown participant characteristics. This supports interpretation of a between-group contrast, provided the allocation process is implemented as intended and the analysis respects the randomized groups. Random assignment does not guarantee identical groups, especially in a small trial. The registry record does not state the sequence-generation method, allocation concealment procedures, or the number assigned to each group.
In an open-label study, participants and study personnel are not described as masked to assigned treatment. This can matter for outcomes that involve judgment, treatment decisions, reporting, or follow-up behavior. Death from any cause is a comparatively direct event, but open-label conduct can still affect study procedures and the collection of other outcomes. The record does not describe steps used to limit such effects.
How is overall survival analyzed in general?
For time-to-event outcomes, follow-up begins at a defined starting point and continues until the event or the end of usable observation. The registry specifies randomization as the starting point and death from any cause as the event. If a participant’s event time is not observed during follow-up, the participant’s information is generally treated as censored at the last known observation time. Censoring does not mean the participant had the event at that time; it means the event time is not known beyond the recorded follow-up. The actual censoring definition and handling in this trial are not reported in the registry record.
A median survival estimate describes the midpoint of the estimated time-to-event distribution. A confidence interval communicates the statistical uncertainty around an estimate under the method used to calculate it. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry specifies a 95% confidence interval as the planned dispersion measure, but does not post the estimate or interval, nor identify the calculation method.
Some time-to-event analyses compare groups using a hazard ratio. In general, a hazard ratio summarizes a relative contrast between event rates over follow-up under a specified model. Its interpretation depends on the analysis assumptions and on what the reported estimate represents. No hazard ratio is reported for this primary outcome. The registry’s general note says that only sponsor-reported hazard ratios are used, but the posted record contains no such primary-outcome estimate.
What can a significance test establish?
A significance test assesses how compatible the observed data are with a specified null hypothesis under the test’s assumptions. A p-value is not the probability that a treatment works, nor does it describe the size or clinical importance of an effect. A confidence interval adds information about the range of values compatible with the data and analysis. Neither a p-value nor an interval is reported for the primary outcome in this record. There is therefore no basis for describing the survival comparison as statistically significant or nonsignificant.
The registry’s planning note describes a two-sided significance level of 0.05, equal allocation, and a normal approximation for sample-size illustrations. It also says that the effect to detect is expressed as a stated fraction of the observed effect, and that time-to-event planning uses a total event count. These are planning assumptions, not results from the trial. The record does not report the effect estimate needed to interpret an illustration based on an observed effect. It does not report the original design’s sample-size justification, and the planning illustration should not be called observed power.
Why do analysis details matter?
Interpretation depends not only on the endpoint but also on the analysis population and rules for handling participants’ data. An intention-to-treat analysis generally retains participants in their assigned groups, while other approaches may require different eligibility or adherence rules. The registry record does not identify the primary analysis population, describe exclusions, or state how treatment discontinuation or crossover would be handled. These choices cannot be reconstructed from the enrollment figure alone.
For survival outcomes, the number and timing of observed events influence the information available to estimate group differences. Follow-up duration, censoring, and completeness of outcome ascertainment also affect precision. The record states a follow-up timeframe of 24 months but does not report follow-up completeness, event timing, or group-specific event counts for the primary analysis. The listed deaths in the safety information do not substitute for those details: they are not presented as a comparative survival analysis.
The registry record reports one outcome measure and zero analyses. This distinction is important: naming an endpoint describes what was intended to be measured, whereas an analysis result gives an estimate from observed data under stated methods. Here, the endpoint is defined, but the comparative analysis and its uncertainty are not posted. Statistical interpretation should stop at that reporting boundary rather than infer a result from design details or descriptive safety counts.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity concerns arise when a study conducts several statistical tests or examines multiple endpoints, subgroups, time points, or analysis choices. In general, conducting many tests without an appropriate plan can increase the chance of finding an apparently notable result by chance. A prespecified strategy may identify a primary endpoint, order the tests, or adjust the interpretation. The registry names overall survival as the primary outcome and reports one outcome measure, but does not describe a multiplicity strategy. Whether additional analyses were planned outside the posted record is not reported in the registry record.
The registry reports zero analyses, so it does not provide a set of primary or secondary outcome estimates to assess for multiplicity. It also does not report interim analyses, stopping boundaries, subgroup analyses, or an analysis plan. Those details should not be inferred from the phase designation or from the fact that the trial was terminated. The reason for termination and whether any formal interim review informed it are not reported in the registry record.
Missing-data interpretation is also limited. The record does not describe loss to follow-up, censoring rules, missing outcome information, or sensitivity analyses. For a time-to-event endpoint, participants may have incomplete event-time information if follow-up ends before death is observed. Appropriate interpretation then depends on how observation ends and on assumptions about censoring. The registry gives a follow-up timeframe of 24 months but does not report how completely that follow-up was obtained.
The analysis populations are not specified. The record does not say whether the primary analysis was intended to include all randomized participants, only participants who received assigned treatment, or another defined population. Nor does it state how protocol deviations or treatment discontinuation were handled. These omissions prevent readers from assessing whether the reported enrollment corresponds to the population used for any analysis. Since no comparative primary-outcome analysis is posted, the registry record does not allow evaluation of these issues against actual analysis results.
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 |
|---|---|---|---|
| Trans Sodium Crocetinate Plus SOC | 11 | 19 | 57.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Trans Sodium Crocetinate Plus SOC | 14 of 19 |
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 |
|---|---|
| Trans Sodium Crocetinate Plus SOC | 19 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Trans Sodium Crocetinate Plus SOC |
|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 4 of 19 |
| Deep vein thrombosis | Vascular disorders | 3 of 19 |
| Depressed level of consciousness | Nervous system disorders | 2 of 19 |
| Seizure | Nervous system disorders | 2 of 19 |
| Vasogenic cerebral oedema | Nervous system disorders | 2 of 19 |
| Cognitive disorder | Nervous system disorders | 1 of 19 |
| Gait disturbance | General disorders | 1 of 19 |
| Pancytopenia | Blood and lymphatic system disorders | 1 of 19 |
| Steroid withdrawal syndrome | Endocrine disorders | 1 of 19 |
| Diarrhoea | Gastrointestinal disorders | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Trans Sodium Crocetinate Plus SOC |
|---|---|---|
| Fatigue | General disorders | 10 of 19 |
| Constipation | Gastrointestinal disorders | 8 of 19 |
| Thrombocytopenia | Blood and lymphatic system disorders | 7 of 19 |
| Headache | Nervous system disorders | 7 of 19 |
| Oedema peripheral | General disorders | 6 of 19 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 6 of 19 |
| Nausea | Gastrointestinal disorders | 5 of 19 |
| Vomiting | Gastrointestinal disorders | 5 of 19 |
| Aphasia | Nervous system disorders | 5 of 19 |
| Confusional state | Psychiatric disorders | 5 of 19 |
Serious events with the highest arm-level rate: pulmonary embolism (21.1%), deep vein thrombosis (15.8%), depressed level of consciousness (10.5%), seizure (10.5%), vasogenic cerebral oedema (10.5%).
The registry lists a safety group titled Trans Sodium Crocetinate Plus SOC. It records 19 participants at risk for serious adverse events, with 11 affected. For other adverse events, it records 19 at risk and 19 affected. The entry also lists 14 deaths. These are descriptive registry figures and should be read as recorded, not as estimates of comparative risk between treatment strategies.
The listed serious adverse-event terms and percentages are pulmonary embolism, 21.1%; deep vein thrombosis, 15.8%; depressed level of consciousness, 10.5%; seizure, 10.5%; vasogenic cerebral oedema, 10.5%; and cognitive disorder, 5.3%. The registry presents these as the top serious terms. It does not give event-specific counts, timing, duration, severity grades, or attribution to treatment for these terms.
The safety entry does not present a separate comparable adverse-event group for standard care alone. Although the trial design includes a standard-care comparator, the posted safety figures do not establish whether an event was more or less frequent in one assigned group than the other. An event occurring during a trial is not, by itself, evidence that the intervention caused it. The registry record does not report investigator attribution or a comparative safety analysis. The counts also do not explain whether participants experienced more than one event.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, open-label, parallel-group phase 3 trial was registered to compare TSC plus standard care with standard care alone in newly diagnosed glioblastoma biopsy-only subjects. It specifies overall survival as the primary outcome and defines the measure as time from randomization to death from any cause. The record also states a follow-up timeframe of 24 months, reports enrollment of 19, and marks the study terminated.
Those design and status details do not provide an estimate of treatment effect. The registry does not report median overall survival by group, a comparative estimate, a confidence interval, a hazard ratio, or a test result. It also lists no analyses. Therefore, the posted record does not establish whether the treatment strategies differed in overall survival or how precise any such difference might be. The absence of a reported result should not be interpreted as evidence that the strategies were equivalent or that one was superior.
The safety entry provides descriptive figures for the group titled Trans Sodium Crocetinate Plus SOC, including serious adverse-event and other adverse-event counts, selected serious terms, and deaths. These figures do not constitute a controlled comparison, establish causality, or resolve the missing survival analysis. The registry does not report event attribution or the context needed to compare safety between assigned groups.
The trial’s termination is relevant to how readers assess the completeness of the record, but the reason for termination is not reported. The record does not say whether follow-up continued as planned, whether a formal analysis was performed outside the registry, or why no primary-outcome analysis is posted. No conclusion about those circumstances can be drawn from the status alone.
The appropriate interpretation is limited: the registry describes a planned clinical question and reports some enrollment and safety information, but it does not provide the primary outcome result. Any claim about efficacy, lack of efficacy, or the comparative balance of benefits and risks would go beyond the information recorded.
13. Why This Trial Matters Statistically
This trial illustrates the distinction between a registered design and an interpretable treatment-effect result. The registry identifies a randomized comparison, a primary endpoint, treatment strategies, and a follow-up timeframe. Those elements show what the study was intended to assess. They do not by themselves show what the observed survival data indicated.
For biostatisticians and clinical researchers, the missing comparative result is especially consequential because overall survival is the designated primary endpoint. A median and confidence interval, together with a clearly defined group comparison and analysis population, would allow readers to assess both the estimated outcome and its precision. The registry does not post those quantities. Without them, the primary clinical question remains unanswered in the public record.
The enrollment of 19 and the terminated status also make transparent reporting important. Neither fact explains the absence of a primary analysis, and neither should be used to infer the study’s result. A complete account would need to clarify the analysis performed, the follow-up obtained, the reasons for termination, and the handling of participant data. Those details are not reported in the registry record.
The safety entry offers a further statistical lesson: descriptive counts from one listed safety group are not a substitute for a comparative analysis. Counts and percentages require clear denominators, group definitions, event definitions, and context about attribution and overlap. The registry gives some denominators and selected terms, but does not post an equivalent comparative safety result.
The statistical importance of this record is therefore methodological and reporting-focused. It demonstrates why readers need results, uncertainty measures, and analysis details—not only a trial title, design label, endpoint definition, or safety listing—to judge what evidence a trial contributes.
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 principal limitation for interpretation is that the registry record does not report a comparative result for the primary endpoint. It names overall survival and its intended summary but gives no group-specific medians, confidence intervals, hazard ratio, or analysis result. The record lists zero analyses and indicates that the primary-outcome entry was skipped because fewer than two arms were present for that outcome.
Enrollment is recorded as 19, but group-specific enrollment and the number included in any survival analysis are not reported. Follow-up is described as lasting 24 months, but completeness of follow-up, censoring, missing outcome data, and event timing are not reported. The reason for study termination is also not reported. These gaps prevent assessment of the maturity and completeness of the survival data.
Several design and analysis details are absent. The randomization procedure and allocation concealment are not reported in the registry record. The primary analysis population, statistical method, treatment of protocol deviations, and handling of treatment discontinuation are not reported. The record does not describe interim analyses or a multiplicity plan. The sample-size justification for the trial is not reported; planning illustrations based on an observed effect do not supply that justification or the missing outcome result.
The safety information is limited to the posted group entry and selected serious adverse-event terms. It does not give a comparable safety summary for the standard-care group, event attribution, timing, severity grading, or information on repeated events. As a result, the figures cannot support a comparative safety interpretation.
The registered status, phase, and planned endpoint describe the study, but do not resolve these missing-result limitations. Additional details may exist outside the registry record, but they are not reported in the registry record and cannot be assumed in interpreting the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects — NCT03393000.
- Registry record last updated 2021-07-22; status last verified 2021-07.
- Results first posted 2021-07-22.
- 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
NCT03393000 is a randomized, open-label, controlled, parallel-group phase 3 study sponsored by Diffusion Pharmaceuticals Inc. It concerns newly diagnosed glioblastoma biopsy-only subjects and compares Trans Sodium Crocetinate plus standard care with standard care alone. The standard-care regimen includes radiation therapy and temozolomide followed by post-radiation temozolomide.
The primary endpoint is overall survival, defined as time from randomization to death from any cause, with a stated follow-up timeframe of 24 months. Enrollment is 19. The record lists the study as terminated, with a start date of 2018-01-16 and primary completion date of 2020-11-06.
The posted registry record includes descriptive safety figures but no comparative primary-outcome analysis. The reason for termination, analysis methods, analysis populations, and completeness of follow-up are not reported in the registry record.