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 Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity (NCT01709136), a na phase 2, phase 3 study. The primary outcome is Early and Late Pharmacokinetics of Sirolimus (SRL).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01709136 |
| Phase | Phase 2, Phase 3 |
| Condition | Hypertension |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pittsburgh |
| Results posted | Yes |
2. Clinical Question
Population
Liver transplant recipients who had been stable for at least 3 months and had early nephrotoxicity and/or hypertension attributed to tacrolimus. The registry record reports that three participants were enrolled and that one pharmacokinetic profile was performed for each.
Intervention
Sirolimus. The study description concerns pharmacokinetics of tacrolimus and sirolimus alone and in combination, and the primary objective includes evaluating conversion from tacrolimus to sirolimus.
Comparator
No separate comparator group is reported. The study is recorded as single-group, with allocation listed as not applicable and no masking. Its arms are not a like-for-like control comparison.
Primary question
What are the early and late pharmacokinetics of sirolimus, and what are the safety and efficacy of conversion from tacrolimus to sirolimus in the specified liver transplant recipients? The primary outcome timeframe is 1 year, but numerical outcome results are not reported in the registry record.
This is a question about drug exposure and a proposed treatment conversion, not a randomized estimate of sirolimus versus a control. The registry record also lists secondary outcomes concerning pharmacokinetic parameters for tacrolimus and sirolimus, whether sirolimus can substitute for tacrolimus, and whether sirolimus can prevent tacrolimus-related side effects. Those aims do not establish that the corresponding outcomes were measured or analyzed. The record states that three profiles were performed, one for each enrolled patient, and that the study terminated early. It does not report numerical estimates that would answer the pharmacokinetic question or support an estimate of conversion effects.
3. Trial Design
The study is registered as a single-group trial, with allocation listed as not applicable and masking listed as none. Its reported phase is Phase 2 and Phase 3, and its status is terminated. The sponsor is the University of Pittsburgh. The study began in 2005-12, and its primary completion date is 2010-01. Enrollment is recorded as 3.
The intervention listed is sirolimus, a drug. The arm is also named Sirolimus; no separate control arm or arm description is reported. The brief description concerns pharmacokinetics of tacrolimus and sirolimus alone and in combination in liver transplant recipients. The primary objective describes evaluating early and late sirolimus pharmacokinetics, along with safety and efficacy of conversion from tacrolimus to sirolimus, among recipients stable for at least 3 months who had early nephrotoxicity and/or hypertension attributed to tacrolimus.
The registry record says that three pharmacokinetic profiles were performed, one in each of the three enrolled patients. It attributes early termination to FDA blackbox warnings dated 6/11/2009 about sirolimus in liver transplant recipients, noting risk of thrombosis and death. The record’s sentence about the resulting data analysis is incomplete. No further description of enrollment procedures, treatment duration, dosing, follow-up visits, or protocol deviations is reported in the registry record.
With no separate control group, the design cannot provide a like-for-like comparison between sirolimus and another treatment. The fact that the study was terminated early and enrolled three participants also limits how much can be learned from the completed profiles. The registry record does not provide a detailed statistical analysis plan or a sample-size justification for the original trial.
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 | Sirolimus |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Three pharmacokinetics (PK) profiles were performed, one in each of three patients who were enrolled. However, due to FDA blackbox warnings (6/11/2009) about Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.
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 | Sirolimus |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 3 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Early and Late Pharmacokinetics of Sirolimus (SRL), measured over 1 year.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled “Early and Late Pharmacokinetics of Sirolimus (SRL)” and has a timeframe of 1 year. Pharmacokinetics describes how drug exposure changes over time in the body. In general, assessing a drug’s pharmacokinetic profile can help characterize exposure and its variation across participants. That is the general purpose of this type of endpoint; it does not establish a clinical benefit or harm.
The objective connects the pharmacokinetic assessment with the safety and efficacy of conversion from tacrolimus to sirolimus in liver transplant recipients with early nephrotoxicity and/or hypertension attributed to tacrolimus. The secondary outcomes also refer to pharmacokinetic parameters for both drugs. However, the registry record does not report a specific primary parameter, unit, or measure of dispersion. It does not describe the precise sampling schedule or the definition used to distinguish early from late pharmacokinetics.
Most importantly, no numerical primary endpoint results are reported in the registry record. The record states that three profiles were performed, one in each enrolled patient, but does not provide profile values, estimates, or an analysis linking those profiles to safety or efficacy. Therefore, the endpoint’s stated purpose can be described, but its observed results and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record documents a small, terminated, single-group study. Three participants were enrolled, and a pharmacokinetic profile was performed for each. It reports no outcome analyses. Consequently, there are no posted numerical estimates for early or late sirolimus pharmacokinetics, no reported comparison of tacrolimus with sirolimus, and no reported estimate of safety or efficacy for conversion.
The primary outcome has a stated timeframe of 1 year, but a timeframe alone does not provide an outcome value. The registry record gives no primary endpoint unit, parameter, or dispersion measure. Without estimates and their uncertainty, readers cannot judge the magnitude or precision of any pharmacokinetic finding. A confidence interval, in general, expresses a range of values compatible with data and an analysis under stated assumptions. No primary endpoint confidence interval is reported in the registry record.
The absence of a comparator is central to interpretation. In general, a single-group study can describe what was observed among enrolled participants, but it cannot separate a treatment effect from other explanations through a concurrent control comparison. Here, even a descriptive outcome estimate is not reported. The secondary outcome titles indicate intended questions about substituting sirolimus for tacrolimus and preventing tacrolimus-related side effects; they do not establish that those outcomes were analyzed or that either aim was met.
The registry record reports that the study terminated early after FDA blackbox warnings about sirolimus in liver transplant recipients, mentioning risk of thrombosis and death. This is the stated reason for termination, not a report that those events occurred among participants. The adverse-event entries list zero serious adverse events and zero other adverse events among the three participants at risk, while the death field is not reported. These entries should be read as limited registry counts, not as precise evidence about risk.
The record lists four outcome measures and zero analyses. It names secondary outcome topics, but supplies no numerical results for them. It also does not report a detailed analysis plan, missing-data approach, or analysis populations. Taken together, the posted information is insufficient to estimate treatment effects or characterize uncertainty. The appropriate interpretation is that the registry documents the study’s objectives, limited enrollment, early termination, and sparse safety counts, while leaving the planned pharmacokinetic and conversion questions unanswered in its reported results.
9. Statistical Methods Explained
What does a single-group design allow?
The registry record classifies the study as single-group, with allocation not applicable and no masking. In general, a single-group design records outcomes among people receiving an intervention without a separate concurrent control group. Such a design may describe observations in the enrolled group, but it does not by itself provide a controlled estimate of what would have happened under another treatment. Changes observed over time can have explanations other than the intervention, and a direct comparative effect cannot be isolated without a suitable comparison.
That distinction matters for the study’s conversion objective. The record describes evaluating conversion from tacrolimus to sirolimus, but lists sirolimus as the intervention and reports no separate control group. The study’s structure therefore does not support a randomized, like-for-like comparison. Moreover, numerical outcome analyses are not reported, so the registry does not provide a descriptive estimate to interpret either.
What does pharmacokinetic measurement describe?
In general, pharmacokinetics concerns drug exposure over time. A profile can consist of measurements collected at different times and summarized using selected parameters. Which measurements and parameters are appropriate depends on the protocol and the scientific question. The registry record identifies early and late sirolimus pharmacokinetics as the primary outcome and mentions pharmacokinetic parameters for tacrolimus and sirolimus among secondary outcomes. It does not report the specific primary parameter, measurement unit, sampling schedule, or dispersion measure. The three completed profiles are mentioned, but their numerical values are not reported in the registry record.
Repeated measurements within one participant are not equivalent to independent participants. In general, analyses of repeated measurements need to account for their relationship within a person if they are combined. The registry record does not describe how profile measurements were to be analyzed, whether participant-level summaries were planned, or whether any model for repeated observations was used. It also does not identify an analysis population beyond the description of the three enrolled patients whose profiles were performed.
How should estimates and uncertainty be read?
In general, an estimate is a numerical summary of an outcome or contrast, while a confidence interval conveys uncertainty around that estimate under the specified statistical method. Wider intervals generally indicate less precision; narrow intervals indicate greater precision, conditional on the model and assumptions. Neither an estimate nor its interval can be interpreted without knowing what outcome was measured and how it was analyzed. The registry record reports no numerical primary outcome estimate, confidence interval, p-value, or model result. Thus, there is no posted inferential result from which to assess statistical significance or precision.
Dispersion describes how much observations vary. It is particularly relevant when a study reports individual pharmacokinetic profiles or a summary across a small group. The primary outcome’s dispersion field is not reported in the registry record, and no variability estimate is posted. In general, estimates based on few participants are sensitive to individual observations, so the small enrollment is an important constraint. This does not justify calculating or assuming an unreported effect or uncertainty measure.
What are the planning calculations intended to represent?
The registry’s planning assumptions describe illustrations based on an observed effect, not the original trial design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The numerical fraction is not reported in the registry record. For non-time-to-event outcomes, the illustrations are expressed as participants per arm; for time-to-event outcomes, the stated convention is total events using the Schoenfeld method.
These are hypothetical planning calculations, not observed power and not a retrospective measure of whether the study was adequately powered. Their two-arm equal-allocation premise does not match the registered single-group design. The registry record does not report the sample-size justification used when the trial was designed, and the planning assumptions should not be mistaken for it. The observed effect used in the illustrations is not numerically reported in the registry record, so the calculations cannot be independently interpreted from the posted outcome information.
What can be concluded from the listed analysis count?
The registry record lists zero analyses. This means it reports no outcome analyses, not that every possible analysis would have yielded no effect. A missing estimate is not evidence of no effect, and it does not establish that outcomes were unchanged. It means the posted record does not give the numerical findings needed to assess those questions.
In general, a statistical analysis plan specifies how outcomes, populations, missing observations, and multiple tests will be handled. Such choices can affect estimates and uncertainty. A detailed plan, model specifications, covariate adjustments, interim analyses, and inferential test results are not reported in the registry record. Without these details and without numerical analyses, readers cannot evaluate the assumptions behind any treatment-effect claim. The record supports a description of study structure and reported counts, but not an independent statistical assessment of efficacy or pharmacokinetic effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists four outcome measures, including the primary outcome and secondary topics concerning pharmacokinetic parameters for tacrolimus and sirolimus, substitution of tacrolimus by sirolimus, and prevention of tacrolimus-related side effects. Testing multiple outcomes can raise a multiplicity issue: in general, the chance of at least one apparently unusual result can increase when many hypotheses are assessed. Methods such as prespecifying a primary outcome or adjusting inference may address that issue, but no multiplicity strategy is reported in the registry record.
The record lists zero analyses and gives no numerical outcome results. It does not report whether the secondary outcomes were measured, how they were defined, or whether any adjustments for multiple comparisons were planned. No interim analysis plan or statistical analysis plan is reported in the registry record. It would therefore be inappropriate to infer that multiplicity was addressed, or that it affected a particular result.
Missing-data handling and analysis populations are also not reported in the registry record. The record states that three profiles were performed in three enrolled patients, but does not describe whether any other data were incomplete, how incomplete measurements would be handled, or what criteria defined an analysis set. This absence does not establish that data were missing; it means the record does not explain the issue. The sentence describing data analysis after early termination is incomplete, and the registry reports no outcome analyses. Readers therefore cannot determine how the planned outcomes, possible missing observations, or analysis populations were handled.
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 |
|---|---|---|---|
| Sirolimus | 0 | 3 | 0.0% |
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 |
|---|---|
| Sirolimus | 0 of 3 |
The safety entries list the Sirolimus group with three participants at risk, zero affected by serious adverse events, and zero affected by other adverse events. The death count is not reported in the registry record. No top serious adverse-event terms are listed. These entries describe what the registry reports; they do not establish that the risk of an adverse event was absent.
In general, a zero count in a small group is compatible with uncertainty about how often an event might occur in a broader population. It also does not tell readers whether all events were collected, how long participants were monitored, or how events were defined. Follow-up details and further adverse-event collection methods are not reported in the registry record. The death field being unreported should not be interpreted as a reported zero.
The record attributes early termination to FDA blackbox warnings about sirolimus in liver transplant recipients and mentions risk of thrombosis and death. That statement explains the recorded reason for termination; it is not a finding that those events occurred in this study. The posted safety counts are limited and should not be used as a precise estimate of safety risk.
12. What the Result Does, and Does Not, Mean
The record establishes that a study of sirolimus pharmacokinetics and conversion from tacrolimus was registered for liver transplant recipients with early nephrotoxicity and/or hypertension attributed to tacrolimus. It was a single-group study, enrolled three participants, and had three pharmacokinetic profiles performed. It was terminated early, with the record attributing termination to FDA blackbox warnings dated 6/11/2009. These details describe the study and its course; they do not answer whether conversion changed pharmacokinetics or clinical outcomes.
No numerical outcome analyses are reported. As a result, the record does not establish the magnitude, direction, or precision of any pharmacokinetic result. It also does not provide an estimate for the secondary questions about substituting sirolimus for tacrolimus or preventing tacrolimus-related side effects. The presence of those outcome titles signals topics of interest, not successful demonstration of a result.
The safety entries report zero serious and zero other adverse events among three participants at risk. The death field is not reported. These sparse counts cannot establish that an event cannot occur or precisely characterize event risk. Nor should the statement about warnings be confused with an observed trial event.
In general, evidence about a treatment effect requires outcome data interpreted in light of study design, comparator, uncertainty, and analysis methods. This record has no separate comparator, no reported numerical analysis, and limited enrollment. It therefore cannot support a controlled treatment-effect estimate or a confident conclusion about safety or efficacy. It also cannot establish that there was no effect. The appropriately bounded conclusion is that the registry describes a small study that stopped early and does not report the analyses needed to answer its principal pharmacokinetic and conversion questions.
13. Why This Trial Matters Statistically
This trial is statistically notable because its central question combines pharmacokinetic description with a treatment-conversion objective, while its registered design is single-group. Those aims call for careful distinction: a profile can describe exposure in an individual or group, whereas a treatment-effect claim generally requires a clearly defined contrast. With no separate comparator and no reported analyses, the record does not supply that contrast.
The limited enrollment also makes transparent reporting especially important. The record states that three participants were enrolled and that a profile was performed for each. Individual observations can have substantial influence in a small study, and uncertainty may be considerable. General statistical reasoning cautions against treating sparse data as definitive, but the registry supplies no estimates or uncertainty measures with which to quantify the issue for these outcomes.
The early termination is relevant to what could be learned, but the record does not report a revised analysis plan or detailed account of the data analysis. The stated reason for termination was concern reflected in FDA blackbox warnings about sirolimus in liver transplant recipients. That context should be kept separate from the reported adverse-event counts and from any claim about treatment effects.
Finally, planning illustrations based on an observed effect should not be confused with the original design or with observed power. Their stated assumptions use two-arm equal allocation, which is unlike the registered single-group structure. The record does not report the original sample-size justification or numerical outcome analyses. Statistically, this case illustrates why design, measurement, analysis, and reporting must all be considered before interpreting a trial’s aims as evidence that those aims were answered.
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 main trial-specific limitation is the very small enrollment: three participants. The registry record reports one pharmacokinetic profile for each and says the study terminated early. This leaves little information for characterizing variation across participants, and the record does not provide numerical profile results or uncertainty measures.
The study is registered as single-group and has no reported comparator. Consequently, its design is not a like-for-like controlled comparison, even though the objectives concern conversion from tacrolimus to sirolimus and whether sirolimus can substitute for tacrolimus or prevent tacrolimus-related side effects. No numerical analyses are reported for those questions.
The primary endpoint is described by title and timeframe, but its unit, specific parameter, dispersion measure, and sampling details are not reported in the registry record. The outcome list includes four measures, but the record does not report definitions or results for the secondary outcomes. Analysis populations, missing-data handling, multiplicity procedures, and a detailed statistical plan are also not reported. The sentence concerning data analysis after early termination is incomplete.
The serious and other adverse-event counts are reported as zero among three participants at risk, but the death field is not reported. The record does not describe follow-up or adverse-event ascertainment details sufficient to interpret those counts as a precise estimate of risk. These limitations are specific to the information recorded for this study and prevent firm conclusions about pharmacokinetic outcomes, treatment conversion, or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity — NCT01709136.
- Registry record last updated 2023-03-30; status last verified 2023-03.
- Results first posted 2016-04-21.
- 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 record describes a University of Pittsburgh study of sirolimus and tacrolimus pharmacokinetics in liver transplant recipients with early nephrotoxicity and/or hypertension attributed to tacrolimus. It is listed as Phase 2 and Phase 3, single-group, unmasked, and terminated. Enrollment was 3, and the primary outcome concerned early and late sirolimus pharmacokinetics over 1 year.
Three pharmacokinetic profiles were performed, one in each enrolled patient. The record attributes early termination to FDA blackbox warnings dated 6/11/2009 concerning sirolimus in liver transplant recipients. It lists zero outcome analyses and reports no numerical primary endpoint estimates. Serious and other adverse-event counts are zero among three participants at risk; the death field is not reported. The record does not provide enough analysis detail or outcome results to estimate treatment effects or assess their precision.