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 Defibrotide TMA Prophylaxis Pilot Trial (NCT03384693), a na phase 2 study. The primary outcome is Percent of Total Doses of Defibrotide That Were Missed [Feasibility].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03384693 |
| Phase | Phase 2 |
| Condition | Thrombotic Microangiopathies |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled patients age 0 to 30 years receiving autologous or allogeneic hematopoietic stem cell transplant who met high-risk criteria for thrombotic microangiopathy (TMA). The registry describes TMA as a complication in the transplant population and identifies higher-risk groups within that population. Enrollment was 25.
Intervention
Participants received prophylactic defibrotide. The regimen was 6.25mg/kg intravenously every 6 hours for 28 to 35 days, beginning on the day before conditioning was initiated. The study description says administration and adverse events would be monitored through 6 months post-transplant.
Comparator
There was no control group: the design is listed as single group, with allocation recorded as not applicable. The trial therefore does not provide a randomized or concurrent comparison of defibrotide with another treatment or with no prophylaxis.
Primary question
The primary endpoint asks what percentage of total defibrotide doses were missed, using the median and full range from first treatment through day +21 post-transplant. It is a feasibility measure of administering the drug alongside chemotherapy and supportive medications before, during, and after stem cell infusion. The observed median and range are not reported in the registry record. The study also names the number of patients with TMA and the number with severe TMA as secondary outcomes, but their results are not reported in the registry record.
3. Trial Design
This was a phase 2 pilot trial sponsored by the University of California, San Francisco. The design is recorded as a single group, with no masking and allocation listed as not applicable. The trial enrolled 25 participants and is marked completed. The registry lists a start date of 2018-05-01 and a primary completion date of 2020-07-31.
Eligible participants were age 0 to 30 years, undergoing autologous or allogeneic hematopoietic stem cell transplant, and meeting TMA high-risk criteria. The intervention was prophylactic defibrotide, administered intravenously at 6.25mg/kg every 6 hours for 28 to 35 days, beginning the day before conditioning. The study description says participants would be closely monitored for adverse events through 6 months post-transplant.
The primary endpoint concerns the percentage of total doses missed from the first study-drug treatment through day +21 post-transplant. The registry describes this as a feasibility endpoint, assessing administration alongside chemotherapy and supportive medications around stem cell infusion. The endpoint is specified as a median with a full range, but neither its observed median nor its range is reported in the registry record.
The registry names two secondary outcomes: the number of patients with TMA enrolled on the study and the number with severe TMA. Their results are not reported in the registry record. The record lists nine outcome measures overall, but the outcome results needed to assess TMA incidence and severity are not reported in the registry record. Without a comparator arm, the design can describe experience among enrolled participants but cannot isolate a treatment effect from other influences.
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 | Prophylactic Defibrotide |
|---|---|
| STARTED | 25 |
| COMPLETED | 22 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Prophylactic Defibrotide |
|---|---|
| Adverse Event | 3 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: 25 patients who started therapy
| Characteristic | Unit | Prophylactic Defibrotide |
|---|---|---|
| Participants analysed | 25 | |
| Age, Categorical: <=18 years | Participants | 22 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 15 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 7 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 15 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Diagnosis: Leukemia | Participants | 9 |
| Diagnosis: Lymphoma | Participants | 2 |
| Diagnosis: Neuroblastoma | Participants | 14 |
| Recipient CMV (cytomegalovirus) serostatus: Positive | Participants | 14 |
| Recipient CMV (cytomegalovirus) serostatus: Negative | Participants | 11 |
| Donor type: Unrelated | Participants | 1 |
| Donor type: Haploidentical | Participants | 10 |
| Donor type: N/A (Autologous) | Participants | 14 |
| MIBG (Metaiodobenzylguanidine) therapy prior to transplant: Yes | Participants | 4 |
| MIBG (Metaiodobenzylguanidine) therapy prior to transplant: No | Participants | 21 |
| Conditioning backbone: TBI based | Participants | 3 |
| Conditioning backbone: Melphalan based | Participants | 6 |
| Conditioning backbone: Busulfan based | Participants | 2 |
| Conditioning backbone: Other (Autologous) | Participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Percent of Total Doses of Defibrotide That Were Missed [Feasibility], measured over From first treatment with study drug to day +21 post Transplant.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | percentage of missed doses |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of total defibrotide doses that were missed. It is measured from the first treatment with study drug through day +21 post-transplant, and the planned summary is the median with the full range. The registry frames this as a feasibility question: whether the regimen can be administered while patients are also receiving chemotherapy and supportive medications before, during, and after stem cell infusion.
As a general statistical concept, a missed-dose measure can describe treatment delivery rather than a clinical outcome. A low or high value, if reported, would need interpretation in relation to how doses were scheduled, which participants contributed data, and how missed doses were defined. Those details and the observed median and range are not reported in the registry record. The endpoint therefore cannot be quantified from the posted results.
The primary endpoint is distinct from the clinical outcomes of TMA and severe TMA. The registry identifies those as secondary outcomes but does not report their results. Thus, the stated feasibility question is clear, but the posted record does not give the endpoint estimate needed to judge the observed level of dose delivery.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial record describes a completed, single-group study with enrollment of 25 participants. Its primary endpoint is a feasibility measure, the percentage of defibrotide doses missed, summarized by the median and full range over the stated follow-up window. The observed median and range are not reported in the registry record. This omission prevents a direct description of how many doses participants missed or how variable dose delivery was.
The registry also identifies TMA and severe TMA as secondary outcomes, but does not report their results. Consequently, the posted record does not give an observed TMA incidence, a count of severe TMA cases, or a precision estimate for either outcome. The absence of these results in the registry record should not be interpreted as evidence that no cases occurred.
The safety summary lists 25 participants at risk for serious adverse events and 3 affected. It lists 25 at risk for other adverse events and 0 affected, and records 0 deaths. Bleeding is listed among the top serious adverse event terms at 12.0%. These are descriptive figures from a small, single-group trial; they do not establish whether an event was caused by defibrotide or distinguish treatment-related events from events associated with transplantation or other care. The registry does not report additional detail needed to assess event timing, severity gradations, or attribution.
With no control group, outcome frequencies cannot be interpreted as comparative evidence. Any TMA events observed in this group would not by themselves establish whether prophylaxis changed risk. Conversely, missing outcome results do not establish that the intervention had no effect. The record also does not report an adjusted analysis, a formal estimate of treatment effect, or confidence intervals for the principal outcomes.
The reasonable statistical reading is therefore narrow: the registry documents the trial’s intended feasibility measure, a participant count, and selected safety summaries, but does not report the primary endpoint estimate or the named TMA outcome results. The posted data support description of the design and reported safety counts, not a conclusion about efficacy or the magnitude of any treatment effect.
9. Statistical Methods Explained
What does the single-group design allow?
The registry classifies the trial as single group, with allocation not applicable and masking none. Participants received the prophylactic defibrotide regimen; the record does not describe a concurrent control group. As a general statistical explanation, a single-group study can characterize outcomes and treatment delivery among enrolled participants. It cannot, on its own, separate the effect of the intervention from other causes of observed outcomes, such as the underlying transplant course or differences among participants.
This distinction matters especially for outcomes such as TMA. A count in one treated group is a description of that group, not a comparative effect estimate. A randomized comparison is not part of this design, and the registry does not report a comparison with an untreated group or another regimen.
What does the median and full range mean?
The primary endpoint is the percentage of total doses missed, summarized by a median and full range. In general, the median describes the middle of an ordered set of participant-level values and is less influenced by extreme values than the arithmetic mean. The full range describes the lowest and highest values. These summaries can convey both a typical observed value and the spread across participants, but they do not show the detailed distribution or explain why participants missed doses.
The endpoint’s observed median and range are not reported in the registry record. The registry also does not report the participant-level distribution, a confidence interval, or the rules used to define the dose denominator and handle incomplete records. Thus, the choice of summary is known, but the numerical result and some details needed to reproduce its interpretation are absent.
How should uncertainty be understood?
General explanation: a confidence interval expresses uncertainty around an estimate under a stated statistical model and analysis. It is not a guarantee that the true value lies in the interval. Wider intervals generally indicate less precision, while narrower intervals indicate more precision under the model. The registry record does not report confidence intervals for the primary endpoint or the named TMA outcomes, so their precision cannot be assessed from the posted results.
Enrollment was 25. With a limited number of participants, estimates of uncommon outcomes may be particularly imprecise. This is a general statistical consideration, not a calculation of this trial’s precision. The record does not provide an outcome estimate or interval from which to quantify uncertainty.
Why do planning calculations not establish observed evidence?
General explanation: sample-size planning asks how many participants or events might be needed under specified assumptions to detect a selected effect with a chosen operating characteristic. Such calculations depend on assumptions about the effect size, variability or event rate, allocation, and analysis. They are planning illustrations, not observed results and not evidence that a study had a particular probability of success after it was conducted.
The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. It also distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. Those assumptions do not describe this single-group trial’s design. The trial did not allocate participants between two arms, and the record does not report sample-size justification or a planned power calculation for its actual design. The illustrative assumptions therefore should not be read as the trial’s own design plan.
What does over-dispersion mean in general?
General explanation: for count outcomes, some statistical models assume that the variability is linked to the mean in a particular way. Over-dispersion means the observed variability is greater than that assumption allows. If ignored, standard errors can be too small and uncertainty can be understated. This concept may matter in studies of event counts, but the registry record does not report a count model, a dispersion assessment, or an analysis of the TMA outcomes. It would be inappropriate to infer that such a method was used.
Overall, the posted record identifies the design and the primary endpoint’s summary form, but does not report the primary estimate, its precision, or an inferential analysis of TMA outcomes. Statistical interpretation must remain descriptive rather than comparative.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures and identifies the percentage of missed defibrotide doses as the primary endpoint. It names two secondary outcomes: the number of patients with TMA and the number with severe TMA. The results for these outcomes are not reported in the registry record. The record also lists zero analyses, and does not report inferential tests, confidence intervals, or a statistical analysis plan.
Multiplicity arises when several outcomes or statistical tests are examined. As a general statistical concept, testing many hypotheses can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry does not report whether or how multiplicity was handled. It would not be appropriate to assume a correction, a hierarchy among secondary outcomes, or a prespecified testing strategy.
The record does not report how missing endpoint data were handled, whether all enrolled participants were included in each outcome analysis, or how the analysis population was defined. The primary endpoint description gives a measurement window but not a missing-data rule or a denominator rule. These omissions limit assessment of possible bias if participants had incomplete dose or outcome information. No missing-data method should be inferred from the endpoint description alone.
Accordingly, the posted record does not support a complete review of multiplicity, missing-data handling, or analysis populations. These are unreported details, not evidence that a particular procedure was or was not used during study conduct.
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 |
|---|---|---|---|
| Prophylactic Defibrotide | 3 | 25 | 12.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Prophylactic Defibrotide | 0 of 25 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Prophylactic Defibrotide | 0 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Prophylactic Defibrotide |
|---|---|---|
| Bleeding | General disorders | 3 of 25 |
Serious events with the highest arm-level rate: bleeding (12.0%).
The registry safety summary lists 25 participants at risk for serious adverse events and 3 affected. For other adverse events, it lists 25 at risk and 0 affected. It records 0 deaths. Bleeding appears among the top serious adverse event terms at 12.0%.
These figures are descriptive summaries. They do not show whether the events were judged related to defibrotide, occurred at a particular time, or were associated with transplantation or other treatments. The record does not report those details. The serious adverse event count should not be treated as a causal estimate or as a comparison with another treatment, because this trial had no control group.
The bleeding figure is a listed percentage, but the registry summary does not provide event-level detail or further context for interpreting it. The safety counts also do not establish that events absent from the summary did not occur; they describe what is recorded in the posted summary. Given the single-group design and enrollment of 25, the figures are best read as a limited account of observed safety reporting, not as a comparative assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2 pilot trial enrolled 25 high-risk hematopoietic stem cell transplant patients and administered prophylactic defibrotide according to a specified regimen. It describes a primary feasibility endpoint based on the percentage of missed doses and identifies TMA and severe TMA as secondary outcomes. The record also includes selected safety counts.
However, the primary endpoint’s observed median and full range are not reported in the registry record. The results for the named secondary outcomes are also not reported. Without those estimates, the posted record cannot show how feasible administration was in practice or how frequently TMA or severe TMA occurred among participants. The missing results must not be read as zero missed doses, zero TMA cases, or any other particular outcome.
The safety figures describe 3 participants affected by serious adverse events among 25 at risk, 0 affected by other adverse events among 25 at risk, and 0 deaths; bleeding is listed at 12.0% among the top serious terms. These observations do not establish that defibrotide caused, prevented, or had no effect on any event. A single-group study lacks a concurrent comparator for estimating what would have happened under a different approach.
General statistical interpretation: evidence about an intervention depends not only on the observed estimates but also on their uncertainty, the analysis methods, and the study design. Here, the registry record does not report the principal outcome estimates or precision measures. The defensible conclusion is limited to what the record documents: the study’s design, intended measures, enrollment, and selected safety summary. It does not establish efficacy, comparative safety, or a treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically important as an example of why feasibility and clinical outcomes should be kept distinct. The primary measure concerns missed doses, which addresses whether a complex regimen could be delivered alongside transplant-related care. TMA and severe TMA are separate clinical outcomes. A feasibility measure can inform how an intervention was administered, but it cannot substitute for reported clinical outcome results.
The single-group structure also defines the scope of inference. It can describe enrolled participants’ experience, but without a comparator it cannot estimate a relative treatment effect. This is particularly relevant when outcomes may also be influenced by the transplant setting and participant risk. The design does not make the descriptive observations meaningless; it means they answer a narrower question.
Transparent outcome reporting is essential for statistical interpretation. The registry identifies the primary endpoint and two secondary outcomes, yet their observed results are not reported in the registry record. Without estimates and measures of precision, readers cannot assess either the size or uncertainty of the feasibility and TMA outcomes. The posted safety counts offer some descriptive information, but do not overcome those gaps or provide causal evidence.
The trial record therefore illustrates the difference between a protocol question and an answer supported by posted results. The intended questions are identifiable, but the missing outcome values and analysis details constrain what can be learned statistically. Clear reporting of endpoint estimates, uncertainty, analysis populations, and missing-data handling would be necessary for a fuller assessment.
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.
Several limitations are specific to the information recorded for this trial. First, the primary feasibility endpoint is defined, but its observed median and full range are not reported in the registry record. The named secondary outcomes—patients with TMA and patients with severe TMA—also lack reported results. This prevents direct estimation of the outcomes the trial set out to describe.
Second, the study is single group, with no comparator. The safety summary and any clinical outcome counts therefore cannot be interpreted as treatment-versus-control differences. The registry also does not report confidence intervals or other precision measures for the outcomes.
Third, the registry record does not report the analysis populations, how missing endpoint information was handled, the denominator used for missed-dose percentages, or the details of outcome ascertainment. It lists nine outcome measures but names only the primary endpoint and two secondary outcomes in the available trial description. It does not report a multiplicity strategy or statistical analysis plan.
Finally, enrollment was 25, and the safety information is a limited summary rather than event-level reporting. The record does not give timing or attribution for the serious adverse events. These limitations restrict interpretation to the design and posted descriptive safety figures; they do not justify assumptions about unreported results or methods.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Defibrotide TMA Prophylaxis Pilot Trial — NCT03384693.
- Registry record last updated 2021-09-16; status last verified 2021-09.
- Results first posted 2021-09-16.
- 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
This completed phase 2 pilot trial enrolled 25 patients age 0 to 30 years undergoing autologous or allogeneic hematopoietic stem cell transplant who met TMA high-risk criteria. It used a single-group, unmasked design with prophylactic defibrotide at 6.25mg/kg intravenously every 6 hours for 28 to 35 days, starting the day before conditioning.
The primary endpoint was the percentage of doses missed, summarized by median and full range through day +21 post-transplant. Its observed result is not reported in the registry record. Results for the named secondary outcomes—TMA and severe TMA—are also not reported. Safety reporting lists 3 participants with serious adverse events among 25 at risk, 0 with other adverse events among 25 at risk, 0 deaths, and bleeding at 12.0% among the top serious terms. Without a control group or reported outcome estimates, the record supports descriptive interpretation only.