Reparixin in Pancreatic Islet Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reparixin in Pancreatic Islet Transplantation (NCT01220856), a randomized phase 2 study. The primary outcome is The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5.

2. Clinical Question

3. Trial Design

This was a phase 2, multicenter, randomized, open-label, parallel-assignment pilot study of reparixin following islet transplantation in patients with type 1 diabetes. The registry lists the study as completed, with enrollment of 9. The recorded start date is 2010-07-28, and the primary completion date is 2013-04-30.

The trial compared reparixin plus immunosuppression with immunosuppression only. The arm descriptions identify reparixin as a continuous intravenous infusion into a central vein, given at 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. The available description of when the infusion began is truncated, so its full timing instructions are not reported in the registry record. The comparator description also ends before its full regimen is available.

Random allocation and parallel assignment define the broad comparison, but the method used to generate the allocation sequence, concealment of allocation, and any stratification factors are not reported in the registry record. The study was open label, meaning masking was not used. How the absence of masking was addressed during endpoint assessment is not reported in the registry record.

The posted primary endpoint results list 6 participants in the reparixin arm and 3 in the no-experimental-intervention arm. These are the arm sizes reported with the primary outcome; the registry defines the efficacy population as randomized patients who received the transplant. Details about withdrawals, protocol deviations, or whether all randomized patients were included in other analyses 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy 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.

Population: Safety Population: All patients who were randomized into the study were included in the safety population.

6. Primary Endpoint

The registry lists the primary outcome as The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5, measured over day 75 +/- 5 post-transplant.

The primary endpoint is the percentage of patients who were insulin-independent following a single infusion of islet cells, assessed at day 75 +/- 5 post-transplant. The registry defines insulin independence as freedom from exogenous insulin for 14 or more consecutive days, together with adequate glycemic control. This definition makes the outcome more specific than simply stopping insulin: patients also had to meet the listed measures of glucose and HbA1c control.

The glycemic criteria include an HbA1c level < 7%; a fasting glucose level not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week, based on capillary glucose measurement at least 7 times in a 7-day period; and a 2-hour postprandial glucose level not exceeding 180 mg/dL (10 mmol/L) more than 4 times a week, based on capillary glucose measurement at least 21 times in a 7-day period.

A percentage is a binary-outcome summary: each participant either meets the stated endpoint definition or does not. It gives a clinically interpretable description of how often the defined outcome was recorded in each arm, while not describing the degree of glycemic control among those who did not meet the full definition. The registry reports 0.0% in each arm. Details about adjudication, handling of incomplete measurements, and the precise analysis procedure for this endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this?

As a general statistical explanation, a binary outcome classifies each participant into one of two categories for the defined assessment: the endpoint is met or it is not met. A percentage expresses the share meeting the definition in an arm. For this trial, the registry reports the primary outcome as a percentage of patients and lists 0.0% for each arm. The endpoint's operational definition matters: insulin independence required both a period without exogenous insulin and specified glycemic control.

A percentage is easy to interpret, but it is only a point estimate. It does not by itself show how uncertain the estimate is. Confidence intervals are commonly used to describe uncertainty around an estimated percentage and a difference between groups. The registry does not report confidence intervals for this endpoint, so the uncertainty around the posted percentages is not quantified in the record.

What does randomization contribute?

As a general principle, random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. That supports a causal comparison when the trial is adequately conducted and analyzed, but randomization does not guarantee that every characteristic will be balanced, especially in a small study. The registry describes the study as randomized, but the sequence-generation method, allocation concealment, and any balancing factors are not reported in the registry record. The posted group sizes are 6 and 3.

The study used parallel assignment: participants were assigned to one arm rather than receiving both study conditions in sequence. It was open label, so masking was not used. In general, lack of masking can affect care, participant behavior, and subjective assessments. The primary endpoint uses defined insulin and glucose criteria, but the registry does not state who assessed whether those criteria were met or whether an independent review process was used.

What can be concluded from the arm percentages?

The posted percentages are descriptive summaries. Both are 0.0%, so the record does not display a difference in the primary outcome percentages. A formal treatment comparison would usually quantify the difference or another contrast and describe its uncertainty, potentially using a confidence interval and a statistical test. No such comparison is reported in the registry results, and the record lists no analyses. A descriptive similarity in this small study is not proof of equivalence; equivalence requires an appropriate prespecified margin and an analysis designed to evaluate it. Such a margin and analysis are not reported in the registry record.

For a binary endpoint, the choice of measure can also matter. A difference in percentages expresses an absolute contrast, while a ratio-based measure expresses a relative contrast. These measures answer different questions. No comparative effect estimate is reported, and none should be inferred from the two posted percentages alone. Because both reported percentages are zero, a relative comparison would also require careful handling; the registry does not report one.

Why does over-dispersion matter?

As a general explanation, over-dispersion means that observed variability is greater than a statistical model expects. It can arise when outcomes are more alike within subgroups or centers than a simple model assumes, among other reasons. When present, a model that ignores over-dispersion may understate uncertainty and produce overly narrow intervals or overly optimistic tests. This trial is described as multicenter, but the registry does not report center-level outcome information or a model that accounts for center effects. The posted primary outcome does not include a dispersion estimate, and the record does not report a model-based analysis.

How should the planning illustrations be read?

As a general statistical explanation, planning calculations can estimate the group size needed to detect a chosen effect under stated assumptions. The registry's planning illustration uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; its target effect is a stated fraction of the observed effect. These are planning assumptions, not descriptions of the trial's original design process. The registry explicitly characterizes the illustration as computed from the observed effect, not from the trial's own design.

The posted primary outcome has no observed separation between the two percentages, and the registry says values are missing or not estimable for a two-arm comparison. No planning group-size estimate is therefore reported alongside this endpoint. A planning illustration, when available, is not the number of participants actually studied and is not evidence that the trial had a particular probability of detecting an effect. The trial's original sample-size justification and statistical plan are not reported in the registry record.

For time-to-event outcomes, planning calculations may instead be expressed in terms of an event total, whereas other outcomes may be expressed as participants per arm. That distinction is general; the primary endpoint in this trial is a binary percentage, not a time-to-event outcome. No additional sample-size calculation should be read into the posted primary result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Reparixin", "No Experimental Intervention")
n      <- c(6, 3)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Reparixin  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  No Experimental Intervention  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or analyses are assessed. As a general statistical principle, making many tests can increase the chance of finding an apparently notable result by chance unless the analysis plan accounts for that multiplicity. The registry lists 22 outcome measures, but reports no secondary outcome results and lists no analyses. Whether multiplicity adjustments were planned, and which outcomes were designated as primary in the full analysis plan, are not reported in the registry record.

The primary endpoint is reported for the efficacy population, defined as all patients who were randomized and received the transplant. That definition is not identical to a statement that every randomized participant was analyzed regardless of treatment received or transplantation status. The registry does not report an intention-to-treat analysis definition, a per-protocol population, or how participants with missing endpoint assessments were handled.

Missingness is important for this outcome because meeting the definition depends on insulin use and repeated glucose measurements, as well as HbA1c. The record does not report whether all required measurements were available for each participant, how incomplete measurements were classified, or whether any imputation or sensitivity analysis was performed. These details are not reported in the registry record, so the posted percentages cannot be used to determine how missing data may have affected the results.

The registry's description of the analysis population and the absence of posted secondary results limit interpretation. No adjustment method, missing-data procedure, or prespecified hierarchy of outcomes is reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (33.3%), hemorrhage (33.3%), anemia (16.7%), gastrointestinal hemorrhage (16.7%), nausea (16.7%).

The registry reports serious adverse event information separately for the two arms. In the reparixin arm, 3 of 6 participants were recorded as affected by a serious adverse event; in the no-experimental-intervention arm, 1 of 3 was affected. These are participant counts as presented in the registry, not a comparative risk analysis. The record also reports 0 deaths in each arm.

For other adverse events, the registry records 6 of 6 participants affected in the reparixin arm and 3 of 3 in the no-experimental-intervention arm. The registry does not provide enough detail in these summary counts to establish the severity, duration, or clinical importance of each event, or whether some participants experienced more than one event.

The listed serious adverse event terms include diarrhea and hemorrhage, each reported at 33.3%, and anemia, gastrointestinal hemorrhage, nausea, and peritoneal hemorrhage, each reported at 16.7%. The registry does not provide event-level context in these summaries, so the terms should not be treated as proof that reparixin caused an event. Interpretation of safety comparisons is limited by the small arm sizes and the open-label design. The record does not report a formal statistical comparison of adverse events.

13. What the Result Does, and Does Not, Mean

The main result is that the registry reports 0.0% insulin independence in each arm at day 75 +/- 5 after a single islet cell transplantation. The outcome uses a demanding, explicit definition: participants had to be free of exogenous insulin for 14 or more consecutive days and meet the listed glycemic-control criteria. The posted percentages therefore describe whether participants met that whole definition, not every aspect of graft function or glucose management.

The result does not demonstrate that reparixin and immunosuppression alone have the same effect. A lack of difference in the posted point estimates is not the same as evidence of equivalence, particularly when the arm sizes are 6 and 3 and no confidence intervals or formal comparative analysis are reported. The result also does not establish why no participants were recorded as meeting the endpoint or whether other outcomes might tell a different story. No secondary outcome results are posted.

The record describes a randomized study, which is a useful design feature for comparative inference, but it was open label. Details about allocation procedures, endpoint assessment, missing-data handling, and the statistical analysis plan are not reported in the registry record. Those omissions restrict assessment of potential bias and the precision of the comparison.

The safety summaries report serious adverse events in both arms and no deaths in either arm. They are descriptive counts, not evidence that an event was caused by a particular intervention or that the treatments have comparable safety. The study's small size limits what can be learned about uncommon events. Overall, the posted results characterize this pilot's recorded primary outcome and safety counts; they do not establish a broader treatment effect or settle the question for other settings or patient groups.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized design and a clear endpoint definition are only part of a statistical interpretation. The study asks a focused question about insulin independence after islet transplantation, and it defines that outcome using both insulin use and glycemic criteria. That specificity helps clarify what the endpoint means, but it also means that the reported percentage is not interchangeable with a broader measure of transplant function or glucose control.

The contrast between the study's comparative aim and its posted result is statistically instructive. The registry reports the same primary percentage in both arms, but the small arm sizes and lack of reported confidence intervals leave the precision of that comparison unclear. Without a reported formal analysis, the percentages should be read descriptively rather than as a test of whether the treatments differ or are equivalent.

The record also highlights the value of transparent reporting. Details about allocation, missing data, multiplicity, and the statistical plan affect how results can be interpreted, yet those details are not reported in the registry record. The registry lists many outcome measures but no secondary results and no analyses. A reader therefore cannot assess whether other outcomes support, qualify, or conflict with the primary result.

Safety summaries provide another lesson: participant counts and event terms describe what was recorded, but they do not establish causation or allow a precise comparative safety conclusion. The small study can offer a pilot-level description, while leaving substantial uncertainty about the frequency and pattern of outcomes beyond those observed. Statistically, its value lies in showing how endpoint definition, reporting completeness, and precision shape interpretation—not in proving a broad treatment conclusion.

15. 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 outcome is based on small reported arm sizes: 6 participants receiving reparixin and 3 receiving no experimental intervention. The registry reports 0.0% in each arm but does not provide confidence intervals or a formal between-arm analysis. The precision of the percentages and of any comparative effect is therefore not quantified in the record.

The study was open label. The registry does not report who assessed endpoint status, whether assessment was independently reviewed, or how the trial addressed potential effects of knowing treatment assignment. Although the trial is described as randomized, the method of sequence generation, allocation concealment, and any stratification are not reported in the registry record.

The endpoint definition depends on insulin use, HbA1c, and repeated glucose measurements over specified periods. The registry does not report completeness of those measurements, rules for classifying participants with missing measurements, or sensitivity analyses for missing data. It also does not report withdrawals, protocol deviations, or whether all randomized participants were included in the primary analysis.

There are 22 outcome measures listed, but no secondary outcome results are posted and no analyses are listed. The statistical plan, multiplicity procedures, and original sample-size justification are not reported in the registry record. The posted serious and other adverse event summaries are also limited: they do not establish causality, describe event timing, or provide a formal comparative analysis. These limitations constrain conclusions about both efficacy and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reparixin in Pancreatic Islet Transplantation — NCT01220856.
• Registry record last updated 2021-03-11; status last verified 2021-02.
• Results first posted 2021-03-11.
• 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.

19. Record Summary

This completed phase 2, multicenter, randomized, open-label, parallel-assignment pilot study examined reparixin following pancreatic islet transplantation in patients with type 1 diabetes. Enrollment was 9. The registry lists a start date of 2010-07-28 and a primary completion date of 2013-04-30.

The primary endpoint was the percentage of patients meeting the defined insulin-independence outcome at day 75 +/- 5 after a single infusion. The posted result is 0.0% in each arm, with reported arm sizes of 6 for reparixin and 3 for no experimental intervention. The registry reports serious adverse events affecting 3 of 6 participants in the reparixin arm and 1 of 3 in the comparator arm, with 0 deaths in either arm. No secondary outcome results or formal analyses are posted. Confidence intervals, missing-data methods, and the statistical analysis plan are not reported in the registry record.