Study of In-line Pressure Using Various Techniques of Subcutaneous Administration of Fluids Enabled by Human Recombinant Hyaluronidase (INFUSE-AT1A): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of In-line Pressure Using Various Techniques of Subcutaneous Administration of Fluids Enabled by Human Recombinant Hyaluronidase (INFUSE-AT1A) (NCT01116102), a randomized phase 4 study. The primary outcome is Maximum Measured In-line Fluid Pressure.

2. Clinical Question

The central statistical question is whether the infusion technique factors corresponded to different pressure profiles over the infusion period. The primary endpoint was measured repeatedly: each minute during the first 15 minutes, every 5 minutes during the next 45 minutes, and every 15 minutes thereafter until infusion ended. A profile over time can contain more information than a single summary, but it also raises questions about which time points or summaries should be compared and how repeated measurements are handled. Those choices are not reported in the registry record.

The listed procedures varied in more than one feature. Consequently, any comparison among groups could reflect a difference in catheter or needle, flush, rate scheme, or a combination of these factors, depending on the specific comparison. The record does not state a single prespecified contrast isolating one factor. Nor does it report group-level pressure estimates that would allow readers to assess the magnitude or precision of any difference.

3. Trial Design

This was a phase 4, randomized, parallel-group study with no masking. The registry lists enrollment of 20 and status as terminated. The start and primary completion are both recorded as 2010-05. The study was intended to characterize in-line pressure during subcutaneous infusion of Lactated Ringer's solution preceded by recombinant human hyaluronidase, and to evaluate safety and tolerability.

The intervention descriptions identify technique combinations involving a 24 ga plastic catheter or 25 ga metal butterfly needle, a 3 mL Lactated Ringer's solution flush or no flush with the HYLENEX dose, and either a single-step or up-titrated infusion-rate scheme. Each description specifies a single 150 U subcutaneous HYLENEX dose and a planned 1000 mL Lactated Ringer's infusion. The rate descriptions distinguish an initial rate followed by a later rate, or a staged increase. The complete duration information for all listed schemes is not reported in the registry record.

Randomization can reduce systematic differences between groups when allocation is implemented as intended, but it does not guarantee balance in a small study. The record does not report the randomization sequence method, allocation concealment, or whether any stratification was used. With no masking, participants and study personnel were not masked according to the registry. The record does not explain whether pressure measurement or assessment of technical challenges was masked.

The primary endpoint used the per-protocol population. The registry states that two subjects were excluded because of a technical error in in-line pressure measurement. It does not report the number analyzed in each technique group or provide participant flow by group. Secondary outcomes were the number of attempts needed for successful catheter or needle placement, cumulative fluid volume delivered, and technical challenges encountered during infusion. Results for these outcomes 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.

Only the first 6 of 8 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Per protocol (two subjects excluded due to technical error in in-line fluid pressure measurement)

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Measured In-line Fluid Pressure, measured over each minute for the first 15 minutes of fluid infusion, every 5 minutes for the next 45 minutes of infusion, and every 15 minutes thereafter until the end of infusion.

The primary endpoint was maximum measured in-line fluid pressure, in psi. It represents the highest pressure measured during a 15 sec period in the delivery line at a specified time after infusion began. Pressure was assessed repeatedly: each minute for the first 15 minutes, every 5 minutes for the next 45 minutes, and every 15 minutes thereafter until infusion ended. The registry describes the endpoint parameter as a mean and its dispersion as the full range.

In-line pressure is a process measure of the infusion system during delivery. Recording it over time can help describe how pressure behaves under different technique conditions, rather than relying only on whether the full planned fluid volume was delivered. The maximum within a measurement period focuses on the upper end of pressure during that interval; the mean and full range can convey the center and spread of recorded values, if those results are reported.

The registry record does not give the pressure values, group means, full ranges, or the number of observations contributing at each time point. It also does not report a prespecified summary of the repeated measurements or a statistical model for comparing pressure profiles. Therefore the endpoint definition explains what was intended to be measured, but it does not establish whether pressures differed among techniques or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods explain how study observations are turned into estimates and how uncertainty around those estimates is assessed. For this study, the registry defines a repeated pressure endpoint but does not report the pressure analyses or results. The concepts below are general explanations, not a description of unreported procedures used in this trial.

What does a mean and full range describe?

General: A mean is a measure of the center of a set of observations. A full range reports the smallest and largest observed values, describing the span of those observations. The range is sensitive to extreme values and does not, by itself, show how values are distributed between its endpoints. A mean and range can therefore complement one another, but they do not replace the individual observations or an uncertainty estimate for a group comparison. Here, the registry states that the endpoint was characterized by a mean and full range, but does not publish the pressure values or clarify how observations were combined across time.

Why does repeated measurement matter?

General: Measurements taken from the same participant over time are usually related. A participant's successive pressure readings cannot automatically be treated as independent observations. A method that accounts for within-participant correlation can avoid treating repeated readings as if they came from unrelated people. It can also use the time structure to estimate how groups differ across the course of infusion. The choice of method depends on the scientific question and data structure. The registry does not report a repeated-measures model or other method for handling correlation in the pressure readings.

There is also a distinction between a comparison at a particular time and a comparison of trajectories. A time-specific contrast asks whether groups differ at one scheduled measurement. A trajectory contrast asks whether the pattern of change over the infusion differs. If many time points are tested separately, the chance of at least one apparently unusual result can rise. A prespecified primary time point, summary, or overall test can help define the main question, but the registry record does not identify such a choice.

What would an uncertainty interval convey?

General: A confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but interpretation also depends on which quantity is estimated and whether the method is appropriate. An interval for a group mean is not the same as an interval for a difference between groups. To interpret the technique comparison, a contrast and its uncertainty would be more informative than separate group summaries alone. The registry does not report confidence intervals for the primary endpoint.

A statistical test and an estimate answer related but different questions. A test evaluates compatibility of data with a specified null hypothesis under a model. An estimate describes the size and direction of a contrast, while its uncertainty indicates how precisely it is known. A test result alone would not show whether a difference was practically important; conversely, a non-significant result would not establish that two techniques are equivalent. No test results or equivalence margin are reported in this record.

Why can missing or unusable measurements matter?

General: Missingness can reduce information and may affect interpretation when the probability of a missing observation is related to the unobserved value or to group assignment. For a pressure profile, missing readings at selected times could make group trajectories harder to compare. A technical error in measurement is a distinct reason for an observation to be unusable, but the impact depends on how many measurements were affected and whether the problem was distributed similarly across groups. The registry identifies two subject exclusions for technical measurement error in the per-protocol population, but does not report the group-specific details or the method used for other missing readings.

The per-protocol population is the stated analysis population for the primary endpoint. General: A per-protocol analysis commonly focuses on participants who meet specified criteria for inclusion in the analysis, whereas an analysis based on assigned groups would retain participants according to randomization. These approaches can answer different questions and may be affected differently by exclusions. The criteria for this study's per-protocol population, aside from the stated technical exclusions, are not reported in the registry record. No additional analysis population is described.

What do planning illustrations tell readers?

General: A sample-size calculation uses assumptions about a target effect, variability, significance level, allocation, and analysis method to illustrate how much information a design might need. A calculation based on an effect observed in the same small study is a planning illustration, not evidence that the study had a particular probability of detecting an effect after the data were collected. It should not be described as observed power. In this record, the stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effect fractions based on an observed effect. However, the registry does not identify a single comparison for this multi-technique, multi-time-point endpoint, and does not report the outcome estimates needed to interpret a particular illustration.

Over-dispersion is a general concern when outcome variability exceeds what a simple model assumes. If a model understates variability, its uncertainty estimates may be too small and its intervals too narrow. The registry does not report a model for the pressure endpoint or evidence about whether over-dispersion was assessed; it is therefore not possible to say whether this issue arose in this study.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical questions are tested, such as comparisons across multiple techniques, outcome measures, or time points. If each is treated as an independent opportunity to find a difference, the chance of at least one false-positive result can increase. General approaches include defining a primary comparison in advance, using an overall test, or adjusting inference across a family of tests. The appropriate approach depends on the intended question and analysis plan.

This study included repeated pressure assessments and several technique combinations, as well as secondary outcomes for placement attempts, cumulative fluid volume, and technical challenges. The registry does not report a primary between-group contrast, a hierarchy of outcomes, a multiplicity adjustment, or a plan for selecting time points. It is not possible to determine from the registry record how multiple comparisons would have been handled.

The primary endpoint used a per-protocol population, and two subjects were excluded because of technical error in pressure measurement. The registry does not report additional missing-data counts, the pattern of missing measurements, or an imputation or sensitivity-analysis method. It also does not report analysis-population definitions beyond the primary endpoint's per-protocol description. As a result, the possible effect of missing observations and exclusions on the pressure comparison cannot be evaluated.

These omissions do not establish that the study had no analysis plan; they mean that the plan is not reported in the registry record. In particular, the record does not state how repeated observations, multiple comparisons, or incomplete data were handled.

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 non-serious adverse event terms

The registry lists serious adverse events for each of the eight named technique groups. In every group, the number at risk is reported alongside zero participants affected by serious adverse events. These figures describe the registry's serious-event counts; they do not establish that serious events are impossible or that the techniques have equivalent safety.

For other adverse events, the number affected equals the number at risk within each listed group. The group-level counts are small, and the registry does not provide event terms, severity, timing, duration, or whether events were considered related to the intervention. The counts therefore cannot show which events occurred or how burdensome they were. They should not be interpreted as counts of distinct event types.

Death counts are not reported in the registry record. Definitions for serious and other adverse events and the safety observation period are also not reported. These limits matter when interpreting a safety summary: counts depend on how events were defined, collected, and attributed. The reported figures are descriptive and should be read separately from the unreported pressure endpoint results.

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

The registry record describes a randomized comparison of subcutaneous infusion techniques following HYLENEX, with in-line pressure as the primary endpoint. It identifies the pressure measurement schedule, the per-protocol analysis population, and the reason for two subject exclusions. It also reports group-level adverse-event counts. These details clarify what the study set out to measure and what safety counts were recorded.

However, the record does not report the primary pressure results, secondary outcome results, or statistical analyses. It therefore does not establish whether pressure profiles differed between groups, which technique had higher or lower pressure, or how precisely any difference was estimated. The absence of results is not evidence that the groups were the same.

The randomized design is relevant to comparisons between assigned technique groups, but interpretation still depends on adequate reporting of allocation, analysis populations, missing measurements, and the statistical method. The registry does not report the randomization implementation details, a prespecified primary contrast, or how repeated observations were analyzed. The study's termination status is recorded, but the reason for termination is not reported in the registry record.

The safety counts should likewise be interpreted within their limits. No serious adverse events affected participants are reported in the groups, while other adverse events affected all participants listed at risk. Without event descriptions, severity, and observation details, these counts cannot characterize the nature of the events or establish comparative safety.

In short, the available information supports a description of study design and measurement, not a conclusion about the comparative pressure results or the overall effect of one infusion technique versus another. The posted information does not permit a judgment about clinical benefit, and no such conclusion follows from the design description alone.

13. Why This Trial Matters Statistically

This trial illustrates a statistical challenge common to studies of procedures or delivery techniques: the endpoint can be measured repeatedly, while the intervention itself varies across several implementation features. A pressure profile may be more informative than one isolated measurement, but it also requires a clear definition of the comparison and a method that accounts for repeated observations within participants.

The study also highlights the importance of analysis-population reporting. The primary endpoint was evaluated in a per-protocol population, with two subjects excluded for a technical measurement error. Transparent participant flow and group-specific information about exclusions help readers assess how much data contributed to each comparison and whether the analysis population remained comparable across randomized groups.

A further statistical lesson concerns the difference between design information and results. Randomization and a planned endpoint do not by themselves demonstrate a difference or establish precision. Outcome estimates and uncertainty intervals are needed to describe what the data show. Since those pressure results are not reported in the registry record, the intended measurement framework can be discussed, but its findings cannot be interpreted.

Finally, multiple technique groups and time points create a need for a prespecified analysis strategy. Defining the primary contrast and approach to multiplicity helps prevent selective emphasis on particular comparisons. The registry does not report these elements, so readers cannot determine how the study would distinguish a primary finding from exploratory comparisons. This makes the record useful for understanding the question and design, while leaving the statistical conclusions unresolved.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation for interpretation is the absence of reported pressure results and analyses. The registry defines the primary endpoint but provides no group means, full ranges, time-specific estimates, confidence intervals, or tests. The direction and size of any differences are therefore unknown from the record.

The primary endpoint was measured repeatedly over the infusion, but the record does not report how those repeated measurements were summarized or modeled. It also does not specify a single primary contrast among the technique groups. The multiple components of the techniques make it difficult to attribute any hypothetical difference to one feature without a defined comparison.

The endpoint analysis excluded two subjects for technical error in pressure measurement. The record does not report which groups were affected, how many pressure measurements were unusable, or how incomplete time series were handled. The per-protocol criteria beyond this stated exclusion are not reported.

The study is listed as terminated, but the reason for termination is not reported in the registry record. Randomization methods, allocation concealment, and the sample-size justification are also not reported. The planned enrollment is recorded as 20, but no outcome-based precision assessment can be made without results.

Safety interpretation is limited by the absence of event descriptions, severity, timing, and death counts. The record also does not describe the safety observation period or event definitions. These omissions prevent a fuller comparison of safety experiences across technique groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of In-line Pressure Using Various Techniques of Subcutaneous Administration of Fluids Enabled by Human Recombinant Hyaluronidase (INFUSE-AT1A) — NCT01116102.
• Registry record last updated 2011-10-24; status last verified 2011-10.
• Results first posted 2011-10-18.
• 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

NCT01116102 is a phase 4, randomized, parallel-group study with no masking, listed as terminated and with enrollment of 20. It examined HYLENEX-facilitated subcutaneous infusion of Lactated Ringer's solution in healthy volunteers using technique combinations that varied by catheter or needle, dose flush, and infusion-rate scheme.

The primary endpoint was maximum measured in-line fluid pressure, assessed repeatedly during infusion and described using a mean and full range. The analysis population was per protocol; two subjects were excluded because of technical error in pressure measurement. Secondary outcomes concerned placement attempts, cumulative fluid volume, and technical challenges.

The registry record does not report pressure results, secondary outcome results, statistical analyses, or a reason for termination. It reports no serious adverse events affecting participants in the listed groups and reports other adverse events affecting all participants at risk; event details and death counts are not reported.