Rapid Infusion Of Immune Globulin Intravenous (IGIV) In Patients With ITP: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rapid Infusion Of Immune Globulin Intravenous (IGIV) In Patients With ITP (NCT00220727), a randomized phase 2 study. The primary outcome is Free Hemoglobin.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, controlled, open-label crossover study. Enrollment was 8, and the registry record gives the status as completed. The listed study start was 2003-07 and the listed primary completion was 2003-10. The sponsor was Grifols Therapeutics LLC.

The crossover arrangement exposed participants to both infusion rates in different sequences. Group 1 received IGIV-C at 0.08 mL/kg/min for the first infusion and 0.14 mL/kg/min for the second. Group 2 received the rates in the opposite order. The record describes the first infusion as occurring at week 0 and the second as occurring before week 6. It does not state how the order was generated or whether any period or carryover effects were considered in the analysis.

Masking was listed as none, so the study was open-label. The intervention was IGIV-C, 10% Caprylate/Chromatography Purified. The primary outcome was free hemoglobin at 24 hours after treatment. The primary outcome summaries report 7 participants at each rate, with a mean and standard deviation for each condition. Because the study is a crossover, observations at the two rates may be related when they come from the same participant; the registry record does not provide participant-level paired measurements or a description of how that relationship was handled.

The registry record does not report further details of the randomization procedure, the sample-size justification, an interim analysis plan, or the statistical analysis plan. Those design details cannot be inferred from the crossover structure alone.

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.

First Infusion (Week 0)

Second Infusion (Week <6)

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Free Hemoglobin, measured over 24 hours after treatment.

Free hemoglobin, measured in g/dL 24 hours after treatment, was the primary endpoint. The registry record describes it as a measure to assess hemolysis. The endpoint is a continuous laboratory measure, and the posted summaries use the mean and standard deviation to describe the values at each infusion rate.

In general, a laboratory marker can provide a measurable way to assess a biological process. A mean describes the average observed value in a group, while a standard deviation describes how spread out individual values are around that average. Neither summary by itself indicates how precisely the difference between treatment conditions has been estimated. That requires a comparative estimate and an uncertainty measure, such as a confidence interval, or an appropriate inferential test.

The registry record specifies the measurement time as 24 hours after treatment, but does not provide a more detailed endpoint definition, a threshold for interpreting free hemoglobin, or a clinically meaningful difference. It also does not state whether the endpoint was analyzed as a within-participant change, a comparison between periods, or another form of crossover analysis. The posted endpoint summaries therefore describe the recorded arm-level values, but do not answer how large or precise the rate comparison is.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the mean and standard deviation describe?

The primary outcome is continuous, so the registry record summarizes it using a mean and standard deviation. The mean is the arithmetic average of the recorded free hemoglobin values in a condition. The standard deviation describes how dispersed those values are around their mean. The posted mean is 13.06 g/dL with a standard deviation of 1.778 at 0.08 mL/kg/min, and 12.37 g/dL with a standard deviation of 2.644 at 0.14 mL/kg/min. These quantities describe the observed distributions; they are not a direct estimate of the uncertainty in the comparison.

In general, a confidence interval expresses a range of values compatible with the data and an analysis model, and communicates the precision of an estimate. A standard deviation is not a confidence interval: it describes participant-level spread rather than the uncertainty around a treatment contrast. No confidence interval for the rate comparison is reported in the registry record.

Why does the crossover structure matter?

In a crossover study, participants receive multiple conditions in sequence. When the same participant contributes an outcome under each condition, the measurements are related rather than independent. A paired analysis uses the within-participant differences and their variability. That analysis can be more informative than treating observations as unrelated, but it depends on the paired data and on assumptions about the sequence and timing of treatment periods.

The registry record identifies the study as crossover and gives the two treatment orders, but it does not report a paired contrast, period-specific results, or an account of sequence effects. It also does not state whether carryover was assessed. The separate means and standard deviations do not reveal the correlation between each participant’s measurements. It is therefore not possible to reconstruct the appropriate crossover comparison from the posted summaries alone.

What is missing from the inferential report?

The registry record contains no analysis entries. It does not report a primary-outcome effect estimate, confidence interval, or p-value, nor does it identify a model or a hypothesis test. It does not specify a target difference or an equivalence or noninferiority margin. These omissions matter because the objective uses the idea of similarity: concluding similarity requires a defined criterion and an analysis that evaluates uncertainty against that criterion. A lack of a reported statistically significant difference, if one were reported, would not by itself establish equivalence.

The record identifies free hemoglobin as the primary outcome and gives a measurement time of 24 hours after treatment. It does not describe an adjustment for the crossover sequence, period, or any other covariate. There is no statistical plan in the registry record from which to determine whether an adjusted or unadjusted analysis was intended. No statistical method should be attributed to the study beyond the descriptive mean and standard deviation summaries that are posted.

How should planning illustrations be read?

General sample-size calculations estimate how many participants might be needed under stated assumptions to detect a target effect with a chosen significance level and power. The planning description associated with this record specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not evidence about what the completed study had power to detect. They are not observed power and do not replace a confidence interval or an analysis of the trial data.

For a crossover comparison, a planning calculation may depend on the variability of within-participant differences. The registry record does not provide that variability or enough paired information to assess it. Any planning illustration based on a simpler two-arm approximation should therefore be understood according to its stated assumptions, rather than treated as a complete account of the crossover design. The record does not report the trial’s own sample-size justification, so the posted enrollment cannot be interpreted as evidence that a particular precision or power target was achieved.

Why can over-dispersion matter?

General statistical methods often make assumptions about how variability is distributed. If the actual variability is greater than an analysis assumes, standard errors can be understated and confidence intervals can be too narrow. For a continuous endpoint, the spread of observations and the structure of repeated measurements are central to estimating uncertainty. The posted standard deviations describe spread within each rate summary, but do not provide the within-participant covariance needed for a paired comparison. The record does not report a model that could be evaluated for its variance assumptions.

These methodological points explain what information is needed for a careful analysis; they do not establish that any particular assumption was violated in this study. The available registry results remain descriptive because no inferential analysis is posted.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("IGIV-C, 10% (0.08 mL/kg/Min)", "IGIV-C, 10% (0.14 mL/kg/Min)")
n   <- c(7, 7)
m   <- c(13.057, 12.371)
sp  <- c(1.778, 2.644)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  IGIV-C, 10% (0.08 mL/kg/Min)  7  13.057  1.778  11.413  14.701
CARM  IGIV-C, 10% (0.14 mL/kg/Min)  7  12.371  2.644  9.926  14.816

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures and identifies 1 secondary outcome: the number of subjects with infusion-related adverse events. It does not report analyses for these outcomes; the record lists 0 analyses. No multiplicity procedure, hierarchy of tests, or strategy for controlling the chance of false-positive findings is reported. Without analysis results or an analysis plan, it is not possible to determine how multiple outcomes were handled.

The primary endpoint summaries report 7 participants at each infusion rate, while the total enrollment is 8. The registry record does not explain the difference, identify which participants contributed to each endpoint summary, or state how missing measurements were handled. It does not describe an intention-to-treat, per-protocol, or other analysis population. For a crossover design, it is also important to know whether each participant completed both treatment periods; that information is not reported in the registry record.

The record does not state whether missing values were imputed, excluded, or handled by a model. It also does not provide a flow of participants through the treatment sequences or reasons for missing outcome data. These omissions make it difficult to assess whether the posted summaries represent all enrolled participants or a subset with available measurements. No conclusion about the effect of missing data or multiplicity can be drawn from the posted record.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures are counts of participants affected, not estimates of event risk precise enough to characterize uncommon harms. The registry record lists 0 of 8 participants affected by a serious adverse event in the 0.08 mL/kg/min group and 0 of 7 in the 0.14 mL/kg/min group. The record does not list deaths for either group; death counts are not reported in the registry record.

Zero observed serious events means that no participant in these summaries was recorded as having a serious adverse event. It does not demonstrate that the underlying chance of such an event is zero, and the small enrollment limits what can be learned about uncommon outcomes. The record does not provide serious-event terms because no serious-event terms are listed.

Other adverse events were recorded for 8 of 8 participants at 0.08 mL/kg/min and 7 of 7 participants at 0.14 mL/kg/min. These are participant counts for other adverse events, not necessarily event counts, and they should not be equated with the separately listed secondary outcome of infusion-related adverse events. No analysis of that secondary outcome is reported in the registry record. The counts describe the posted safety information but do not establish that the rates have equivalent safety profiles.

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

The results establish that the registry record contains descriptive summaries of free hemoglobin 24 hours after treatment at each infusion rate. The mean was 13.06 g/dL at 0.08 mL/kg/min and 12.37 g/dL at 0.14 mL/kg/min, with standard deviations of 1.778 and 2.644, respectively; each summary includes 7 participants. The record also reports no serious adverse events in the listed groups, alongside other adverse events affecting all participants represented in each group’s safety count.

These results do not establish that the rates are the same, that one rate is safer, or that either rate changes hemolysis. The registry record does not report a comparative estimate or uncertainty interval for free hemoglobin, and it gives no predefined similarity margin. Descriptive means alone cannot distinguish a real difference from variation that could arise in a small sample. The missing paired data are especially relevant because the study used a crossover design.

The safety counts likewise do not prove that serious adverse events cannot occur, or that there is no difference in safety between rates. A completed study and a stated objective do not, by themselves, resolve the objective. The record’s posted information supports a description of observed outcomes in this study, but not a definitive conclusion about similarity, equivalence, or clinical effect.

These limits concern the information available in the registry record. They do not imply that unreported analyses were never conducted; the record does not report them. The distinction is important: interpretation should be based on the posted data and analysis, rather than assumptions about additional results.

14. Why This Trial Matters Statistically

Statistically, this study is notable for using a randomized crossover design to compare two infusion rates within a small enrolled group. Crossover designs can make within-participant comparisons useful because each participant may serve as their own reference. That benefit depends on having complete paired outcome data and an analysis that accounts for the repeated measurements, treatment order, and study period. The registry record gives the treatment sequences but does not report the paired results or the analysis details needed to judge those issues.

The study also illustrates the difference between descriptive and inferential results. Means and standard deviations show the observed level and spread of free hemoglobin at each rate. Without a comparative estimate and confidence interval, the precision of the rate contrast is not available. This matters particularly when the research objective is framed around similarity: a conclusion of similarity requires an explicit criterion and an estimate precise enough to address it.

The enrollment of 8 and the outcome summaries of 7 participants per rate make careful attention to analysis populations and missingness important. The record does not explain the counts or report a missing-data strategy. The absence of posted analyses also limits assessment of the secondary outcome and any multiplicity considerations.

Finally, the safety data distinguish observed counts from broader safety conclusions. No serious adverse events are listed in the group summaries, but a small study cannot characterize uncommon outcomes with high precision. The record is therefore a useful example of how design labels, descriptive summaries, and analysis reporting each contribute different information—and how much interpretation remains unresolved when the comparative analysis is not reported.

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 enrollment was 8, and the primary endpoint summaries report 7 participants for each rate. The registry record does not explain the outcome counts, identify the participants represented, or report how missing observations were handled. This leaves the completeness of the primary analysis unclear.

The crossover design calls for attention to paired observations, sequence, and period. Although the record lists the order of infusion rates, it does not report participant-level paired values, the number of complete pairs, or a model that accounts for repeated measurements. It also does not report an assessment of carryover. Arm-level means and standard deviations cannot resolve these design-specific questions.

The study was open-label, and the registry record lists no masking. It does not provide further information about outcome assessment procedures. The primary endpoint is a laboratory measure at 24 hours after treatment, but the record does not state a clinically meaningful threshold or a margin for interpreting similarity. This limits interpretation of the objective beyond the descriptive endpoint values.

No inferential analyses are posted. The registry record does not give a treatment contrast, confidence interval, p-value, statistical model, or multiplicity plan. It also does not report the trial’s sample-size justification, analysis populations, or interim analysis details. These items are not reported in the registry record and should not be inferred from the design or enrollment.

The safety summaries are limited to participant counts. The record lists no serious adverse events, but the sample is too small to characterize uncommon events precisely. The other adverse-event counts do not supply a posted analysis of the secondary infusion-related adverse-event outcome. Together, these limitations mean the record supports descriptive reporting rather than a precise comparative conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rapid Infusion Of Immune Globulin Intravenous (IGIV) In Patients With ITP — NCT00220727.
• Registry record last updated 2016-04-27; status last verified 2016-03.
• Results first posted 2014-08-20.
• 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

NCT00220727 was a completed Phase 2 randomized, open-label crossover study of IGIV-C at infusion rates of 0.08 mL/kg/min and 0.14 mL/kg/min in patients with ITP. Enrollment was 8. Participants received the rates in different orders, with the second infusion scheduled before week 6.

The primary endpoint was free hemoglobin, measured 24 hours after treatment. The registry record reports means of 13.06 g/dL and 12.37 g/dL, with standard deviations of 1.778 and 2.644, respectively; each rate summary includes 7 participants. No comparative analysis is posted. Serious adverse events affected 0 participants in either group, while other adverse events affected 8 of 8 and 7 of 7 participants in the respective safety summaries.

The record does not report the analysis plan, missing-data handling, or a statistical comparison. The posted results are descriptive and do not establish similarity between infusion rates.