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 A Study to Evaluate the Efficiency of Intravenously Administered Cyclosporine in de Novo Liver Transplant Recipients (NCT00332462), a non-randomized phase 4 study. The primary outcome is Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00332462 |
| Phase | Phase 4 |
| Condition | Liver Transplantation |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 34 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned de novo liver transplant recipients. The registry record reports enrollment of 34 participants and identifies the intention-to-treat population for the primary outcome. It does not give further eligibility details or describe the clinical characteristics of the enrolled participants.
Intervention
The treatment sequence began with intravenous cyclosporine (Sandimmun® i.v.) during the first 7 days after transplantation, followed by oral cyclosporine microemulsion (Sandimmun® Optoral). The intravenous treatment is described as an infusion given 2 times daily over four hours, starting at 2 X 200 mg/day. Oral treatment is described as twice daily, starting at 8-12 mg/kg/day. The registry record does not provide the complete dose-adjustment description.
Comparator
There was no randomized control group. The study is recorded as nonrandomized and single-group, and the intravenous and oral treatments are described as successive periods in a treatment sequence. They should not be read as independent treatment arms assigned for a like-for-like comparison.
Primary question
The primary question was how many participants experienced biopsy-proven acute rejection during the first 3 months after transplantation while following this treatment sequence. The registry record defines suspected episodes as requiring an allograft biopsy within 48 hours of starting anti-rejection therapy. It also identifies safety assessment and cyclosporine blood-level monitoring as study aims, but does not report a numerical primary-endpoint result.
3. Trial Design
This was a multicenter, open-label, exploratory phase 4 study of cyclosporine in de novo liver transplant recipients. The registry record lists a total enrollment of 34 and classifies the design as nonrandomized and single-group. No masking was used. These design features matter when interpreting the record: there was no randomized assignment to separate treatment groups, and participants and study personnel were not masked to treatment.
The treatment description is sequential. Participants first received intravenous cyclosporine during the first 7 days after transplantation, then continued with oral cyclosporine microemulsion. The intravenous regimen is described as an infusion 2 times daily over four hours, starting at 2 X 200 mg/day. Oral treatment began at 8-12 mg/kg/day, twice daily; the registry description of subsequent dose adjustment is incomplete. The two cyclosporine formulations therefore represent periods in a treatment course, not randomized alternatives.
The primary outcome was the number of participants with biopsy-proven acute rejection during the first 3 months after transplantation, in the intention-to-treat population. The registry also lists safety and tolerability during 6 months as a secondary outcome. It records 34 participants at risk for serious and other adverse events in the intravenous group and 29 in the oral group. The record does not explain the difference in these listed denominators or establish that the groups are directly comparable.
The study is marked completed, but the registry record does not report a numerical result for the primary outcome or a statistical analysis of it. Details such as the recruitment and eligibility criteria, protocol deviations, and the complete dose-adjustment schedule are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Cyclosporine (Sandimmun®) |
|---|---|
| STARTED | 34 |
| Patients Treated With Sandimmun® i.v. | 34 |
| Patients Treated With Sandimmun® Optoral | 29 |
| COMPLETED | 18 |
| NOT COMPLETED | 16 |
Reasons for not completing this period:
| Reason | Cyclosporine (Sandimmun®) |
|---|---|
| Adverse Event | 5 |
| Abnormal Lab Value | 1 |
| Unsatisfactory therapeutic effect | 4 |
| no longer requires study drug | 1 |
| Death | 3 |
| Graft Loss | 2 |
Analysis population for the primary outcome, as defined in the registry: Intention to treat (ITT) population
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 | Cyclosporine (Sandimmun®) |
|---|---|---|
| Participants analysed | 34 | |
| Age Continuous | years | 53.2 (SD 9.6) |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation, measured over 3 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with biopsy-proven acute rejection during the first 3 months after de novo liver transplantation. It is a binary outcome at the participant level: a participant either had a qualifying rejection episode within the specified period or did not. The registry identifies the outcome unit as participants and names the intention-to-treat population.
The endpoint uses biopsy confirmation rather than relying only on clinical suspicion. The registry description says that an allograft biopsy was performed within a 48 hour period of initiating anti-rejection therapy for suspected rejection episodes. A designated pathologist graded biopsies using the Banff criteria as mild, moderate or severe. This provides a stated diagnostic and grading framework for classifying suspected episodes.
Acute rejection is a clinically relevant event after transplantation, so counting participants with biopsy-proven rejection provides a direct descriptive measure of how often the endpoint occurred in the defined follow-up period. However, the registry record does not report the count or proportion of participants meeting the endpoint, nor does it report an uncertainty interval or an inferential analysis. The endpoint definition alone therefore describes what was intended to be measured; it does not establish the observed frequency in this study.
The record identifies the endpoint timeframe as 3 months. It does not explain how participants with incomplete follow-up, missing biopsies, or more than one suspected episode were handled in the analysis. Those details are important for evaluating how completely the endpoint was ascertained and how participant-level outcomes were derived.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the study question and endpoint but does not post a numerical result for biopsy-proven acute rejection. There is no reported number of participants with the primary event, no reported denominator for an analyzed primary-outcome set beyond the stated intention-to-treat population, and no confidence interval or p-value for that endpoint. Consequently, the primary endpoint cannot be interpreted quantitatively from this record.
The study design also limits what any observed count could establish. This was a nonrandomized, single-group study without masking. The intravenous and oral cyclosporine formulations were given in sequence, rather than compared through random assignment. A participant count in such a design can describe events observed during the treatment course, but it cannot isolate the effect of one formulation from the other or establish what would have occurred under a different treatment strategy.
The adverse-event listings report serious events affecting 18 of 34 participants in the intravenous group and 14 of 29 in the oral group. The record also lists other adverse events affecting 34 of 34 and 29 of 29 participants, respectively. These are descriptive counts associated with the treatment-period labels. Because the labels refer to successive treatment periods and the denominators differ, the figures do not constitute a randomized head-to-head comparison. The record does not provide exposure-adjusted rates, participant-level timing, or an explanation of the denominator difference.
The listed serious-event terms include HAEMORRHAGE at 14.7%, CHOLANGITIS at 10.3%, RESPIRATORY FAILURE at 8.8%, ASCITES at 6.9%, BILIARY ISCHAEMIA at 6.9%, and INFECTION at 6.9%. These terms indicate which serious-event categories appear among the registry listings; they do not by themselves identify causal relationships with cyclosporine. The record does not describe how attribution was assessed or whether participants could appear under more than one term.
The study is characterized as exploratory, and the record provides no reported statistical analyses for the outcomes. That absence is important: no estimate of the primary outcome’s precision can be drawn from the posted record, and no formal evidence about a treatment effect is available to interpret. The record supports a description of the planned treatment sequence, endpoint definition and listed safety counts, but not a conclusion about comparative efficacy or the size of a treatment effect.
9. Statistical Methods Explained
The primary endpoint is a binary participant-level outcome: whether biopsy-proven acute rejection occurred during the first 3 months. For a binary outcome, a basic descriptive summary is the number of participants who experience the event and the number assessed. The event count communicates how many participants had the outcome; a proportion can place that count in the context of the population at risk. The registry record does not report the primary event count or an analyzed denominator, so no primary-outcome proportion can be interpreted from it.
What a confidence interval would convey
In general, a confidence interval describes the statistical uncertainty around an estimated quantity, such as an event proportion. A narrower interval indicates greater precision under the assumptions used to construct it; a wider interval indicates less precision. An interval does not remove limitations arising from study design, outcome ascertainment or missing data. No confidence interval for the primary endpoint is reported in the registry record.
Because this is a single-group, nonrandomized study, a primary-outcome estimate, if reported, would describe the observed frequency in the study population and treatment context. It would not provide a randomized estimate of the difference between treatment strategies. The sequential treatment periods also mean that outcomes during one period may be affected by participant characteristics, prior treatment and time since transplantation. A comparison between the period-specific listings would not have the protections of randomization.
Why event counts and exposure matter
Participant counts are useful for showing how many people were recorded with an event, but they do not describe how long each person was observed or exposed to treatment. When follow-up or exposure duration differs, counts alone can be difficult to compare. Rates that account for time at risk may be useful in some settings, but the registry record does not report such rates for these safety listings. It also does not give individual event timing or explain the difference between the 34 participants listed for intravenous cyclosporine and the 29 listed for oral cyclosporine.
Over-dispersion is a general statistical concern when event counts vary more across participants or groups than a simple model expects. Accounting for it can affect uncertainty estimates in models of counts or rates. The primary outcome in this study is defined as a participant count for a binary event, and the record does not report a model, a dispersion estimate or an analysis addressing over-dispersion. It would therefore be inappropriate to infer that such a method was used.
What the analysis record establishes
The registry identifies the intention-to-treat population for the primary outcome. In general, an intention-to-treat analysis aims to retain participants in the group to which they were assigned, preserving the original assignment structure. This study is described as single-group and nonrandomized, so there is no randomized allocation structure to preserve in the usual comparative sense. The record does not provide a detailed operational definition of the intention-to-treat set, a participant flow, or information about exclusions from analysis.
The registry lists zero outcome analyses. This means that no statistical analysis result is posted in the record for the listed outcomes. It does not justify assuming that no analysis was conducted outside the registry, but any such analysis and its methods are not reported in the registry record. In particular, the record does not report a model for the primary endpoint, a confidence-interval method, a hypothesis test, covariate adjustment, or handling of repeated or multiple rejection episodes.
General meaning of a p-value
In general, a p-value measures how compatible observed data are with a specified statistical model and null hypothesis, under the assumptions of that analysis. It is not the probability that a treatment is effective, and it does not describe the magnitude or clinical importance of an effect. No p-value for the primary endpoint is reported, so none can be interpreted for this study.
The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration is a planning calculation, not an observed result or an estimate of the probability that the study detected an effect. The record does not report a primary-outcome effect estimate from which to assess such an illustration, nor does it report the study’s original sample-size justification. Any numerical sample-size planning interpretation beyond the stated assumptions is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one primary outcome and one secondary outcome concerning incidence, safety and tolerability during 6 months. It does not report a multiplicity plan, such as a hierarchy of hypotheses or an adjustment for testing multiple outcomes. Without that information, the handling of multiplicity in any statistical testing cannot be assessed. The record lists zero outcome analyses, so it does not provide a set of reported tests from which to evaluate whether multiplicity adjustments were applied.
The primary population is identified as intention to treat, but the record does not describe how missing primary-outcome information was handled. It does not report the number of participants with complete follow-up, whether every participant had an assessable biopsy outcome, or any imputation or sensitivity analysis. Those omissions matter because incomplete follow-up or absent diagnostic information could affect the count of participants classified with biopsy-proven rejection.
The record does not report a participant flow or explain the adverse-event denominators: 34 are listed for the intravenous period and 29 for the oral period. It is not possible to determine from the record why the risk sets differ, whether the same participants contributed to both periods, or how withdrawals and exposure duration were handled. The listed counts should therefore be read descriptively, not as a direct comparative analysis.
Details of protocol deviations, analysis exclusions, endpoint adjudication beyond the stated pathologist review, and any sensitivity analyses are not reported in the registry record. The absence of these details prevents a full assessment of missing-data assumptions and analysis-population implementation.
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 |
|---|---|---|---|
| Cyclosporine (Sandimmun® i.v.) | 18 | 34 | 52.9% |
| Cyclosporine (Sandimmun® Optoral) | 14 | 29 | 48.3% |
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 |
|---|---|
| Cyclosporine (Sandimmun® i.v.) | 34 of 34 |
| Cyclosporine (Sandimmun® Optoral) | 29 of 29 |
Most frequent serious adverse event terms
| Event term | Organ system | Cyclosporine (Sandimmun® i.v.) | Cyclosporine (Sandimmun® Optoral) |
|---|---|---|---|
| HAEMORRHAGE | Vascular disorders | 5 of 34 | 0 of 29 |
| RENAL FAILURE | Renal and urinary disorders | 2 of 34 | 2 of 29 |
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | 3 of 34 | 1 of 29 |
| CHOLANGITIS | Hepatobiliary disorders | 0 of 34 | 3 of 29 |
| COMPLICATIONS OF TRANSPLANTED LIVER | Injury, poisoning and procedural complications | 2 of 34 | 1 of 29 |
| POST PROCEDURAL HAEMORRHAGE | Injury, poisoning and procedural complications | 2 of 34 | 1 of 29 |
| ASCITES | Gastrointestinal disorders | 0 of 34 | 2 of 29 |
| BILIARY ISCHAEMIA | Hepatobiliary disorders | 0 of 34 | 2 of 29 |
| INFECTION | Infections and infestations | 0 of 34 | 2 of 29 |
| PNEUMONIA | Infections and infestations | 1 of 34 | 1 of 29 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cyclosporine (Sandimmun® i.v.) | Cyclosporine (Sandimmun® Optoral) |
|---|---|---|---|
| CHOLESTASIS | Hepatobiliary disorders | 20 of 34 | 10 of 29 |
| ANAEMIA | Blood and lymphatic system disorders | 18 of 34 | 10 of 29 |
| RENAL FAILURE | Renal and urinary disorders | 18 of 34 | 7 of 29 |
| CONSTIPATION | Gastrointestinal disorders | 15 of 34 | 7 of 29 |
| INSOMNIA | Psychiatric disorders | 13 of 34 | 8 of 29 |
| HYPOTENSION | Vascular disorders | 17 of 34 | 4 of 29 |
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | 16 of 34 | 4 of 29 |
| PROCEDURAL PAIN | Injury, poisoning and procedural complications | 17 of 34 | 2 of 29 |
| HYPERGLYCAEMIA | Metabolism and nutrition disorders | 17 of 34 | 2 of 29 |
| HYPOALBUMINAEMIA | Metabolism and nutrition disorders | 15 of 34 | 3 of 29 |
Serious events with the highest arm-level rate: haemorrhage (14.7%), cholangitis (10.3%), respiratory failure (8.8%), ascites (6.9%), biliary ischaemia (6.9%).
The registry lists serious adverse events by treatment-period label, with 18 of 34 participants affected in the intravenous cyclosporine group and 14 of 29 in the oral cyclosporine group. For other adverse events, it lists 34 of 34 and 29 of 29 participants affected, respectively. These are participant counts in the record, not estimates adjusted for treatment exposure or follow-up time.
The serious-event terms listed with percentages are HAEMORRHAGE at 14.7%, CHOLANGITIS at 10.3%, RESPIRATORY FAILURE at 8.8%, ASCITES at 6.9%, BILIARY ISCHAEMIA at 6.9%, and INFECTION at 6.9%. The record does not specify in these listings whether participants could have more than one serious event, how the percentages were calculated, or whether events were judged related to study treatment. The terms should therefore be read as reported categories, not as proof of causation or as mutually exclusive outcomes.
The treatment labels refer to successive periods in a nonrandomized, single-group study, not randomized comparison arms. Differences in the listed counts cannot be attributed to one formulation rather than another. The death counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that an exploratory phase 4 study enrolled 34 de novo liver transplant recipients and evaluated a sequence of intravenous cyclosporine followed by oral cyclosporine microemulsion. It defines biopsy-proven acute rejection within the first 3 months as the primary endpoint and describes a biopsy and grading process for suspected rejection episodes. These details clarify the question the study set out to address.
The record does not report the numerical primary-endpoint result. It therefore does not show how many participants experienced biopsy-proven acute rejection, how precisely that frequency was estimated, or whether any statistical test was performed. The endpoint definition cannot be substituted for an outcome result.
The safety listings show counts of participants with serious and other adverse events during the treatment periods, as well as several serious-event terms and percentages. These data are descriptive. The study was not randomized, the treatment periods were sequential, and the registry does not provide exposure-adjusted rates, an explanation for the different listed denominators, or a reported assessment of causal attribution. The figures cannot establish that a specific treatment caused or prevented an event, and they do not support a direct efficacy or safety comparison between the two formulations.
More generally, a small single-group study can describe outcomes in its enrolled population, but results from such a design do not by themselves distinguish treatment effects from other influences, including the clinical course after transplantation. Here, the absence of posted primary-outcome results further limits interpretation: the registry record supports understanding the study’s design, endpoint and reported safety counts, but it does not support a conclusion about the magnitude of rejection risk under the treatment sequence or a comparative treatment effect.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of why endpoint definitions, design classifications and posted results must be read together. The registry defines a specific participant-level outcome, biopsy-proven acute rejection during the first 3 months, and describes how suspected episodes were assessed. That gives readers a clear account of the intended measurement, but the absence of a numerical outcome means the endpoint cannot be evaluated quantitatively.
The treatment schedule also illustrates an important distinction between sequential exposure and a comparative trial. Intravenous cyclosporine and oral cyclosporine microemulsion are listed under separate treatment labels, but the design is recorded as nonrandomized and single-group, with the treatments given in succession. Treating these labels as randomized arms would imply a comparison the design does not support. Differences in participant counts across periods may reflect features of the recorded risk sets, but the registry does not explain them.
Safety summaries raise a related issue: event counts are not equivalent to exposure-adjusted rates, and event listings do not establish treatment causality. Denominators, timing, follow-up and attribution methods are needed to interpret safety comparisons. These details are not fully reported in the registry record.
Finally, the record distinguishes a study’s objectives from its posted statistical evidence. It describes the primary question and secondary safety objective, but lists no outcome analyses. Statistical interpretation depends not only on what the investigators intended to measure, but also on the estimates, uncertainty and analysis methods that are actually reported. This distinction prevents study aims from being mistaken for demonstrated findings.
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 primary limitation for interpreting this study is that the registry record does not report a numerical result for biopsy-proven acute rejection, despite identifying it as the primary outcome. Without an event count, analyzed denominator, or uncertainty interval, the principal endpoint cannot be evaluated from the posted record.
The design is nonrandomized, single-group and open-label. The intravenous and oral formulations are described as successive treatment periods, so the study does not offer a randomized comparison between them. It cannot separate outcomes associated with one period from changes related to time after transplantation, prior treatment or other clinical factors. The record does not report an adjusted comparative analysis.
The enrollment was 34, while the adverse-event listings give 34 participants at risk for the intravenous period and 29 for the oral period. The registry does not explain the different denominators, identify the overlap between the listed groups, or provide participant-level exposure and follow-up times. The safety counts therefore have limited comparative interpretation. The record also does not report deaths in the adverse-event listings.
Further details are not reported in the registry record, including complete eligibility criteria, participant flow, missing-outcome handling, protocol deviations, the full dose-adjustment schedule, and methods for statistical analysis. The description of the oral regimen ends before its dose-adjustment details are complete. Multiplicity handling and a detailed sample-size justification are also not reported. These gaps constrain assessment of endpoint ascertainment, analysis populations and the precision or robustness of any results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Efficiency of Intravenously Administered Cyclosporine in de Novo Liver Transplant Recipients — NCT00332462.
- Registry record last updated 2011-03-07; status last verified 2011-03.
- Results first posted 2011-01-11.
- 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
NCT00332462 is a completed, multicenter, open-label, exploratory phase 4 study in de novo liver transplant recipients. It is recorded as nonrandomized and single-group, with enrollment of 34 participants. Treatment began with intravenous cyclosporine during the first 7 days after transplantation and continued with oral cyclosporine microemulsion.
The primary outcome was the number of participants with biopsy-proven acute rejection during the first 3 months, in the intention-to-treat population. A secondary outcome concerned incidence, safety and tolerability during 6 months. The registry record describes the biopsy assessment process and lists adverse-event counts and serious-event terms.
No numerical primary-outcome result or outcome analysis is reported in the registry record. The safety counts are descriptive and do not constitute a randomized comparison of the successive treatment periods. Details on missing data, multiplicity, complete analysis methods and the difference between the listed adverse-event denominators are not reported.