A Trial to Investigate the Relative Efficacy, Safety, and Tolerability of Octaplas LG Versus Octaplas SD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Investigate the Relative Efficacy, Safety, and Tolerability of Octaplas LG Versus Octaplas SD (NCT01063595), a randomized phase 1 study. The primary outcome is Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, crossover phase I trial in healthy volunteers. Its title describes a comparative assessment of Octaplas LG and Octaplas SD. The record lists an enrollment of 63 and a completed status. The listed study dates are 2009-12 for the start and 2010-07 for primary completion.

In a crossover design, participants receive more than one treatment in separate periods, so the comparison can be made within the same participant. As a general statistical principle, a within-participant comparison can account for stable differences between people. It also requires attention to treatment sequence, period effects, and possible carryover from one period to the next. The registry record identifies the crossover model but does not report the treatment sequences, period duration, interval between treatments, or any washout procedure. It is therefore not possible to assess those design details from the record.

Participants received 1200 mL of Octaplas LG intravenously once and 1200 mL of Octaplas SD intravenously once, each in its treatment period. The trial was unmasked, so participants and study staff were not blinded to the treatment being administered, according to the listed masking status. The record does not explain how outcome measurements or safety assessments were conducted in relation to knowledge of treatment assignment.

The primary objective concerned recovery of coagulation factors and other haemostatic parameters. The secondary objective concerned safety and tolerability, including haematological and clinical chemistry parameters and adverse-event monitoring. The listed secondary outcome is concentration of plasmin inhibitor. The record lists three outcome measures, but does not provide a complete account of all measures or their results in the information available.

Randomization is reported, but the method used to generate or conceal the assignment is not reported in the registry record. The protocol’s intended sample size and its justification are not reported in the registry record. Neither are details of interim analyses or the prespecified statistical analysis plan. These omissions limit the ability to judge how closely the reported endpoint and population definitions match the trial’s original plan.

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.

Enrolled in Study and Randomized

Reasons for not completing this period:

First Intervention

Reasons for not completing this period:

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Per protocol population: All participants who had evaluable efficacy measurements in both of the treatment periods.

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 participants who received at least 1 of the study treatments in any study period.

6. Primary Endpoint

The registry lists the primary outcome as Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI, measured over From 5 minutes after the end of plasmapheresis up to 2 hours after the end of study drug administration.

The primary endpoint concerns recovery of coagulation factors I, II, V, VII, VIII, IX, X, and XI. It is a continuous measure, summarized in the record as a mean with standard deviation. Recovery was defined using the maximum percentage change from the factor value measured 5 minutes after the end of plasmapheresis to the value measured at 15 minutes or 2 hours after the end of study-drug administration.

Blood samples were taken 5 minutes after plasmapheresis and at 15 minutes and 2 hours after administration. The record says validated assays were used. The endpoint is intended to describe the short-term change in measured factor levels after each treatment, relative to the post-plasmapheresis measurement. Measuring more than one factor and more than one post-treatment time point captures a range of laboratory responses over the stated observation window.

As a general statistical point, a continuous endpoint retains information about the magnitude of measurements rather than reducing them to categories. In a crossover study, a treatment comparison may use paired measurements from the same participants, but the exact statistical model matters because it should reflect the repeated treatment periods and any sequence or period effects. The statistical method actually used is not reported in the registry record.

The primary endpoint is described as having multiple factor categories and time points. The registry record does not provide a single comparison that combines or prioritizes these measurements, nor does it report factor-specific results, treatment contrasts, uncertainty intervals, or p-values. Consequently, the endpoint definition can be described, but the comparative result and its precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. A mean describes the arithmetic average of observed values, and a standard deviation describes how dispersed those values are around the mean. These summaries can help describe a distribution, but they do not on their own quantify the treatment comparison. For that, readers generally need an estimate of the contrast between treatments and a measure of its uncertainty. Neither is reported for the primary outcome in the registry record.

Why the crossover structure matters

As a general statistical explanation, a crossover study assigns treatments in separate periods, allowing outcomes under both treatments to be observed in the same participant. This structure can reduce the influence of stable participant-level characteristics on the comparison because each participant can serve as their own control. That advantage depends on having usable observations from both periods and on the analysis reflecting the paired structure. The record defines the primary population as participants with evaluable efficacy measurements in both treatment periods, but does not report how many participants met that definition.

Crossover analyses also need to consider whether outcome values change over time or differ by period, and whether the effect of one treatment could persist into the next period. These are general design considerations, not details confirmed for this trial. The record does not report treatment sequence, period length, a washout interval, or any assessment of carryover. It also does not describe the statistical model used to account for the crossover structure. Without those details, it is not possible to determine how the analysis handled within-person dependence or period-related variation.

What the endpoint definition implies

The endpoint is based on percentage change from the factor measurement taken 5 minutes after plasmapheresis. It uses values measured at 15 minutes or 2 hours after study-drug administration and selects the maximum percentage change. This definition creates multiple dimensions to interpret: several coagulation factors and more than one post-administration time point. The record does not specify a single primary factor or time point, nor does it provide a rule for combining results across those categories into one treatment comparison.

When multiple outcomes or time points are examined, multiplicity can become relevant. As a general principle, testing multiple hypotheses can increase the chance that at least one result appears unusual by chance if each is interpreted independently. A prespecified hierarchy, adjustment method, or other analysis strategy can clarify how such results should be interpreted. The registry record does not report a multiplicity strategy or the detailed statistical plan, so it is not possible to determine whether or how this issue was addressed.

Interpreting estimates and uncertainty

A confidence interval is a statistical summary of uncertainty around an estimate. In general, a narrower interval indicates greater precision under the assumptions of the analysis, while a wider interval indicates less precision. A confidence interval should be interpreted alongside the effect estimate and the measurement scale; it does not establish that all values inside it are equally plausible or that a result is clinically important. No confidence intervals or treatment-effect estimates for the primary endpoint are reported in the registry record.

A p-value is also dependent on the statistical model and the null hypothesis being tested. In general, it measures how unusual the observed data, or more extreme data, would be if the null hypothesis and model assumptions held. It does not give the probability that the null hypothesis is true, and it does not convey the size of a treatment difference. The record lists no primary-outcome analyses, so no primary p-value is available to interpret.

Planning illustrations and trial power

The record’s stated assumptions for sample-size planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. It distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes. These are planning illustrations based on an observed effect, not the trial’s own design justification. The protocol’s sample-size justification is not reported in the registry record.

Such planning calculations are not observed power and do not demonstrate that the trial had a particular probability of detecting a true effect. They describe hypothetical sample sizes under stated assumptions. Their interpretation depends on the effect estimate used and on whether the assumptions fit the trial design and outcome. Since the primary outcome has multiple categories and time points and no single comparison is reported, the registry record does not provide the results needed to judge a primary-endpoint planning calculation in context.

In general, over-dispersion means that observed variability is greater than a model expects. When present, it can make standard errors too small if the model does not allow for the additional variability, leading to overly narrow intervals or misleading tests. The registry record does not report whether over-dispersion was assessed or relevant to these outcomes; it should not be assumed to have occurred.

Finally, the analysis population matters. The primary endpoint is defined for a per protocol population with evaluable measurements in both treatment periods. That differs conceptually from an analysis of all randomized participants, which would include participants regardless of whether they completed both periods. The record does not report the analysis population size, participant flow, missingness, or a comparison of analysis populations. Those details would be needed to assess how exclusions and incomplete measurements affected the estimates.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome spans coagulation factors I, II, V, VII, VIII, IX, X, and XI, with measurements at 15 minutes and 2 hours after study-drug administration. The registry record describes recovery using the maximum percentage change across the stated follow-up measurements, but it does not report a single combined comparison or identify a hierarchy among factors and time points. It also does not report whether statistical tests were adjusted for multiple comparisons. Without those details, readers cannot determine how the trial handled the interpretive consequences of examining several related endpoints.

As a general principle, missing outcome measurements can affect both the precision and interpretation of a treatment comparison. In a crossover trial, a participant may contribute complete observations for both treatment periods, incomplete observations for one period, or no evaluable primary measurements. The record defines the primary population as participants with evaluable efficacy measurements in both periods, but does not report its size, the reasons for missing measurements, or how missing data were handled. It is therefore not possible to assess whether missingness could have influenced the primary comparison.

The record does not report a statistical analysis plan, an interim-analysis plan, or the method used for the primary endpoint. It does not state whether the primary analysis was adjusted for treatment sequence, period, or other factors. The stated primary population is per protocol; whether additional populations were analyzed is not reported in the registry record. These omissions leave uncertainty about the prespecified analysis choices and the robustness of any result. Because the primary results themselves are not reported, no sensitivity analysis or alternative analysis can be evaluated.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaphylactic shock (1.7%).

The safety record lists 60 participants at risk for Octaplas LG and 60 for Octaplas SD. One participant in the Octaplas LG group is listed as affected by a serious adverse event, compared with none in the Octaplas SD group. The record identifies anaphylactic shock as the serious-event term and lists 1.7%. These are descriptive registry figures; the record does not provide a statistical comparison or uncertainty interval for the difference between groups.

The record also lists other adverse events affecting 34 participants in the Octaplas LG group and 39 in the Octaplas SD group. These counts are separate from the serious-event count and should not be added to it: the record does not clarify whether participants could appear in both categories or how events were grouped. It also does not provide event-level details, severity breakdowns for the other events, or information about relatedness to treatment.

Deaths are listed as null for both groups. This means the registry record does not report a death count in these entries; it should not be read as a confirmed count of zero. The safety figures describe what is recorded, but do not establish comparative risk, particularly without information on follow-up, event ascertainment, and the analysis approach.

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

This trial asks a focused laboratory question: how recovery of several coagulation factors after Octaplas LG compares with recovery after Octaplas SD in healthy volunteers. The crossover design and repeated sampling were intended to support a short-term comparison within participants. The endpoint definition specifies which factor values and post-administration measurements contribute to the recovery measure.

The registry record does not report the primary outcome values or treatment comparisons. It therefore does not show whether the measured recovery was greater, smaller, or similar under either treatment, nor how precisely any difference was estimated. No conclusion about equivalence or lack of difference can be drawn from missing comparative results. A statistical conclusion would require the actual estimates, their uncertainty, the analysis method, and the number of participants contributing data.

The record does document some safety counts, including one serious adverse event in the Octaplas LG group and none listed for Octaplas SD. It also records other adverse events in both groups. These descriptive entries do not, on their own, establish that one treatment is safer than the other. The registry record does not report a statistical safety comparison, detailed event follow-up, or death counts.

As a general distinction, laboratory changes are measurements of biological responses, while clinical outcomes concern how participants feel, function, or survive. This trial’s primary endpoint is a laboratory recovery measure, and the registry record describes a healthy-volunteer phase I study. The record does not report clinical outcomes that would show how the laboratory measurements relate to patient benefit or harm. Nor does it provide evidence about treatment use in a broader patient population.

The most accurate reading is therefore limited to the design and recorded endpoints: a randomized open-label crossover comparison was conducted, and the registry record describes its intended laboratory and safety assessments. The comparative efficacy result is not reported in the registry record, so the trial’s central treatment contrast cannot be interpreted from the posted information.

13. Why This Trial Matters Statistically

Statistically, the trial is notable for its crossover structure and its repeated measurement of multiple laboratory outcomes. A crossover comparison can make efficient use of within-participant data because each participant receives both treatments. This design also makes the analysis dependent on complete paired observations and appropriate handling of treatment period, sequence, and possible carryover. The registry record identifies the crossover model but does not report those operational or analytic details.

The endpoint illustrates how a seemingly straightforward recovery measure can involve several choices: a reference measurement after plasmapheresis, multiple coagulation factors, more than one follow-up time, and a maximum percentage change definition. Those choices shape the estimand—the precise treatment effect the analysis is intended to describe. Because no single comparative result or hierarchy is reported, readers cannot tell which factor- and time-specific result is meant to carry the primary interpretation.

The record also highlights the distinction between a study’s observed results and planning exercises based on an observed effect. Planning illustrations under stated statistical assumptions do not substitute for an a priori sample-size justification or establish observed power. The protocol’s justification is not reported in the registry record, and the primary outcome results needed to assess the observed comparison are also absent.

Finally, the safety counts are informative as descriptive entries but cannot carry the weight of a comparative safety analysis without details of ascertainment, follow-up, and uncertainty. The trial’s statistical value to readers depends not only on its randomized design, but also on complete reporting of outcome estimates, analysis methods, and participant flow. Those elements are not available in the registry record for the primary comparison.

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 principal limitation is that the primary outcome results are not reported in the registry record. The endpoint definition is present, but there are no factor-specific means, standard deviations, treatment contrasts, confidence intervals, or p-values. The record identifies multiple factors and time points and notes that the primary outcome has several categories or time points rather than one reduced comparison. Consequently, the planned endpoint cannot be evaluated as a comparative result.

The primary analysis population is defined as participants with evaluable efficacy measurements in both treatment periods, but the number meeting that definition is not reported in the registry record. Participant flow, reasons for missing measurements, and missing-data methods are also not reported. This is important for a crossover analysis that depends on observations from both treatment periods.

Although the record says the study was randomized and crossover, it does not report the sequence-generation method, allocation concealment, treatment sequence, period duration, interval between periods, or washout procedures. The statistical model, adjustment for period or sequence, and handling of possible carryover are not reported. The open-label status is stated, but the record does not describe whether outcome assessment could be influenced by knowledge of treatment.

The registry record does not report the protocol’s sample-size justification, an interim-analysis plan, or the detailed analysis plan, including any multiplicity strategy. The sample-size assumptions described for planning illustrations do not establish what the trial was designed to detect. Safety entries do not include a statistical comparison or detailed event follow-up, and deaths are not reported as counts. Together, these limitations prevent a full assessment of the reliability, precision, and scope of the trial’s comparative findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Trial to Investigate the Relative Efficacy, Safety, and Tolerability of Octaplas LG Versus Octaplas SD — NCT01063595.
• Registry record last updated 2014-05-20; status last verified 2014-05.
• Results first posted 2014-05-01.
• 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.

18. Record Summary

The registry record describes NCT01063595 as a completed, randomized, open-label, crossover phase I trial in healthy volunteers, with an enrollment of 63. Participants received 1200 mL of Octaplas LG and 1200 mL of Octaplas SD intravenously once, in separate treatment periods. The primary endpoint assessed maximum percentage change in coagulation factors I, II, V, VII, VIII, IX, X, and XI, using a measurement after plasmapheresis as the reference and measurements after treatment. Safety and tolerability were secondary objectives.

The record lists safety groups of 60 participants at risk for each treatment, one serious adverse event for Octaplas LG, none for Octaplas SD, and other adverse events affecting 34 and 39 participants, respectively. It does not report the primary comparative results, the detailed statistical analysis, the primary analysis-population size, or the protocol’s sample-size justification.