Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex) (NCT00656370), a randomized phase 4 study. The primary outcome is The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS).

2. Clinical Question

The central comparison is between two solutions delivered by the same subcutaneous approach after Hylenex, not between Hylenex and no Hylenex. Since each participant received both solutions in opposite thighs, the Stage 1 comparison has a within-participant feature: each person contributes experience with both infusions. The record’s arm summaries report 15 participants for each solution, but the primary result alone cannot establish whether discomfort differed consistently within individuals.

The study also described a Stage 2 comparison of NS with buffered NS. Stage 2 results are not reported in the registry record. The available primary endpoint results therefore address the Stage 1 NS-versus-LR question in healthy volunteers, rather than the Stage 2 comparison or use in a broader patient population.

3. Trial Design

The registry identifies this as a completed Phase IV, randomized, quadruple-masked, parallel study sponsored by Halozyme Therapeutics. The study began in 2007-12, had primary completion on 2008-01-30, and recorded enrollment of 15. The condition is listed as Healthy. The official title describes the INFUSE-NSLR Study as a double-blind randomized study; the registry’s masking classification is quadruple.

Stage 1 compared NS and LR. Each subject received 500 mL of each solution, with one infusion in each thigh. Immediately before each infusion, the thigh received 150 units of Hylenex. The primary endpoint population is stated as 15 subjects randomized and completing Stage 1. The record’s arm summaries likewise include 15 participants for NS and 15 for LR. Because both solutions were given to each subject, the design description indicates a paired participant-level comparison, even though the registry also classifies the model as parallel.

Stage 2 was described as comparing NS with buffered NS, but results for that stage are not reported in the registry record. The record lists one drug intervention, recombinant human hyaluronidase, and describes the NS and LR groups as receiving their respective solution with Hylenex.

Five secondary outcomes are posted, including infusion flow rate and thigh circumference measures, alongside the primary discomfort endpoint. The registry record does not report the study’s original sample-size justification, detailed allocation procedures, or a full statistical analysis plan. Those details should not be inferred from the randomized label or from the later planning illustrations.

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.

Before assignment: Seven subjects were excluded during screening: 6 did not meet inclusion criteria and 1 withdrew consent. An additional 3 subjects were screened as alternates, but were not enrolled. 15 subjects were randomized and completed stage 1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 15 subjects were randomized and completed stage 1

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 The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS), measured over Approximate times which ranged from zero minutes at baseline to maximal post-infusion of 240 minutes on Day 1.

The primary endpoint is participants’ self-assessment of discomfort at the infusion site using a validated visual analog scale. The scale ranges from 0 mm, defined as no discomfort, to 100 mm, defined as the worst possible discomfort. The endpoint description identifies assessments at approximate times from zero minutes at baseline to maximal post-infusion at 240 minutes on Day 1. The reported summary is a mean with standard deviation.

A VAS is used to capture a participant’s subjective experience on a graded continuum, rather than forcing the experience into a small set of categories. The scale can therefore represent degrees of discomfort, while its meaning remains dependent on how participants interpret and mark it. In this study, the comparison concerns discomfort associated with NS versus LR infusion, with Hylenex preceding both. It does not isolate the effect of Hylenex itself.

In the posted summaries, mean discomfort was 20.0 mm for NS and 9.4 mm for LR. The unadjusted re-calculated mean difference, expressed as LR minus NS, was -10.6 mm. These averages describe the recorded ratings in this small Stage 1 group; they do not by themselves describe how ratings changed over time or how consistently the paired participant ratings differed. The registry record does not report the primary endpoint’s detailed analysis method or a sponsor-reported inferential result.

7. Results Posted in the Registry

• LR Infusion Group: mean 9.40 versus 20.00 on control; difference -10.60 (95% CI -24.10 to 2.90), standardized effect d = -0.56; z-test p = 0.124.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • LR Infusion Group: mean 395.80 versus 384.10 on control; difference 11.70 (95% CI -78.24 to 101.64), standardized effect d = 0.09; z-test p = 0.799.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between LR Infusion Group and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • LR Infusion Group: mean 5.30 versus 5.20 on control; difference 0.10 (95% CI -1.01 to 1.21), standardized effect d = 0.06; z-test p = 0.860.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between LR Infusion Group and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the assessment beyond participant-rated discomfort to include infusion flow rate and local thigh circumference. The posted results show no clear separation between NS and LR in the reported secondary comparisons. Their mean estimates are close, while the associated uncertainty ranges include zero. This broad pattern is directionally consistent with an inconclusive primary comparison, but it does not validate the primary result or demonstrate that the solutions are equivalent.

Flow rate and circumference address different aspects of the infusion experience from the primary VAS measure. A flow-rate result concerns delivery speed, while circumference measures describe a local physical change over the stated assessment period. They can complement a subjective discomfort rating, but they are not substitutes for it. A result on one endpoint should not be treated as a direct explanation of another without a reported analysis linking them.

Five secondary outcomes are posted, while the registry lists two reported analyses with Wilcoxon signed rank tests. The five outcome descriptions include measures beyond the two outcomes with reported test results. Results for the other secondary outcomes are not reported in the registry record. It is therefore not possible to characterize the complete secondary-outcome pattern or to infer unreported findings.

Unadjusted secondary results carry less weight when several outcomes are considered because examining multiple outcomes increases the chance that at least one appears unusual by chance. General statistical practice may address this through prespecified outcome hierarchies or multiplicity adjustments, but the registry record does not report such procedures. The secondary p-values should be viewed as exploratory evidence unless a broader analysis plan is documented. They do not provide independent confirmation of the primary finding, particularly in a small sample and in the absence of reported multiplicity handling.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants Assessed for Safety Measures
• Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution
• Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites
• Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference
• Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh)

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical ideas help explain how the reported results should be read. General explanations in this discussion are not claims about unreported trial procedures.

What does a mean difference represent?

For a continuous measure such as VAS discomfort, a mean summarizes the average recorded value in a group. A mean difference compares two group means. The posted re-calculated primary contrast is defined as LR minus NS: the LR mean is 9.4 mm and the NS mean is 20.0 mm, giving a reported contrast of -10.6 mm. A negative contrast means the first named value in that subtraction, LR, is lower on average. It says nothing by itself about the spread of individual paired differences or whether the difference is important to participants.

The posted standard deviations are 18.3 mm for LR and 19.4 mm for NS. A standard deviation describes variation among the observations around a group mean. It is not the same as a confidence interval, and it does not say how precisely the mean difference is estimated. The within-subject setup matters: if analysis uses paired observations, the relationship between each participant’s two ratings contributes to uncertainty. The registry record does not report the primary analysis method or the within-participant correlation.

How should a confidence interval be understood?

General statistical interpretation: a confidence interval represents uncertainty about an estimated quantity under the method used to calculate it. Narrower intervals indicate greater precision, while wider intervals indicate less precision. The primary interval runs from -24.1 to 2.896 for the LR-minus-NS mean difference. Because this range crosses zero, it does not distinguish a lower mean for LR from no difference or a higher mean for LR at the interval’s bounds. The confidence level and method for the primary interval are not reported in the registry record, so they should not be assumed.

A confidence interval is not a range containing a specified proportion of individual participant values. It also does not demonstrate that all effects inside the interval are equally plausible or equally important. Clinical interpretation would require a relevant threshold for meaningful discomfort differences, and such a threshold is not reported in the registry record.

What does a p-value tell the reader?

General explanation: a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, nor is it a measure of effect size. The primary p-value of 0.124 is an unadjusted re-calculation from posted summary statistics, not a sponsor-reported primary test. The registry reports p-values of 0.93 and 0.67 for the secondary Wilcoxon signed rank tests. A larger p-value does not prove equality, especially when estimates are imprecise.

The reported secondary method, the Wilcoxon signed rank test, is a nonparametric method for paired measurements. In general, it uses the direction and rank of paired differences rather than relying on a normal model for the differences. The registry record does not identify the test used for the primary endpoint. It is therefore inappropriate to assume that the primary endpoint was analyzed by the same test or by a particular paired model.

Why do paired data and small samples matter?

General explanation: paired measurements can be more informative than independent measurements when participant-level observations are related, because each participant can serve as their own comparison. The benefit depends on the size and pattern of within-person differences. Reporting separate means and standard deviations for each solution does not reveal that paired pattern. With 15 participants completing Stage 1, individual observations can have substantial influence on averages and test results. The record does not provide participant-level data or detailed diagnostics, so the influence of unusual observations cannot be assessed.

Over-dispersion is a general concern when the observed variation exceeds what an assumed statistical model can accommodate. In that case, standard errors may be too small and confidence intervals too narrow if the model fails to account for the extra variation. The registry record does not report an over-dispersion assessment or a model for these outcomes. For the continuous endpoints, the standard deviations show variability, but the posted summaries alone cannot establish whether a particular model adequately represents it.

What is the distinction between reported and recalculated results?

The primary mean difference, interval, and p-value are explicitly unadjusted re-calculations from the posted summary statistics. They are not described as the sponsor’s analysis. For the flow-rate and circumference outcomes, the registry record includes Wilcoxon signed rank test results as reported analyses, as well as summary-based mean comparisons. The reported test and the re-calculated mean contrast address related but not identical summaries. Where sponsor-reported and recalculated results disagree, the sponsor’s own analysis takes precedence; the registry record does not identify a discrepancy for these results.

The record lists two reported analyses, corresponding to the secondary outcomes with Wilcoxon signed rank results. It does not report a detailed statistical plan, the primary test, adjustment for multiple comparisons, missing-data procedures, or analysis-population definitions beyond the statement that 15 subjects completed Stage 1. Any explanation of such procedures would therefore be general, not a description of what the investigators did.

11. Confidence Intervals and Precision

The primary mean difference is -10.6 mm for LR minus NS, and its confidence interval extends from -24.1 to 2.896. This interval spans zero and covers values favoring either direction of the mean contrast. Its width reflects limited precision in the estimate, and the sample included 15 participants who completed Stage 1. The registry record does not report the confidence level or calculation method, so the interval should be interpreted by its posted bounds without assigning an unreported level.

The confidence interval is uncertainty about the estimated mean difference, not a description of the range of discomfort ratings among participants. The group standard deviations, 19.4 mm for NS and 18.3 mm for LR, indicate that individual ratings varied around the respective means. The paired participant-level differences are not reported, so the degree to which an individual’s rating under one solution predicts their rating under the other cannot be assessed from these summaries.

For flow rate, the mean difference of 11.7 mL/hr has an interval from -78.24 to 101.6. For thigh circumference percent change, the mean difference of 0.1 has an interval from -1.01 to 1.21. Both intervals include zero and span effects in either direction. These intervals, like the primary interval, do not establish equivalence. No margin defining a sufficiently small difference is reported, and the registry record does not provide confidence levels for these intervals.

Precision is distinct from statistical significance and from practical importance. A point estimate can be near zero while remaining uncertain, and an interval can contain values that would matter in context. The posted estimates should therefore be read as limited-precision evidence from a small volunteer sample, not as definitive estimates for other populations or settings.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for the continuous outcomes in this study; they are not total event counts. The illustrations assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect, with separate rows for planning around 100%, 75%, and 50% of that effect. The trial’s original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm under the stated assumptions for an analysis designed to detect the selected effect with 80% power. The 90% power column uses the same planning framework but targets 90% power. In general, higher planned power requires more participants when the other assumptions remain unchanged. The figures are planning illustrations, not observed power; observed power is not a measure of how conclusively a completed trial answered its question.

Smaller effects require more participants to detect with the same planned power, because a smaller difference is harder to distinguish from random variation. Thus, the rows based on a smaller fraction of the observed effect have larger planning counts. These calculations use the observed effect as a starting point, so they should not be treated as a reliable forecast of a future effect. In a small study, the observed effect itself may be unstable. The curve should be read as a visual expression of the same planning relationship, not as an additional trial result.

These values do not change the number enrolled in this completed study, which was 15. They do not show what sample size the investigators originally intended, and they do not establish whether the trial was adequately designed for its primary question.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -10.600; pooled standard deviation σ = 18.858.
2. n = 2 × (1.96 + 0.842)² × 18.858² / -10.600² = 49.7, rounded up to 50 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -10.6                      # observed difference in means
sigma <- 18.8580221656461                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(656370)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 50 (80% power), 67 (90% power)
 75% of observed effect: n per arm = 89 (80% power), 119 (90% power)
 50% of observed effect: n per arm = 199 (80% power), 267 (90% power)
power.t.test: 50.7 
Simulated power at n = 50 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several endpoints, time points, or comparisons. General statistical explanation: as the number of statistical tests increases, the chance of at least one apparently notable result under a collection of null effects can also increase. Investigators may address this with a prespecified hierarchy, adjustment, or an explicitly exploratory interpretation. The registry record lists a primary discomfort endpoint and five posted secondary outcomes, but adjustment for multiple comparisons and a testing hierarchy are not reported in the registry record.

The registry identifies two reported secondary analyses, both using a Wilcoxon signed rank test. The primary endpoint’s analysis method is not reported. The unadjusted re-calculated primary p-value should therefore not be treated as a documented sponsor test, and the secondary p-values should not be assumed to have been adjusted. Whether other analyses were conducted, or whether any adjustment was used outside the registry record, is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary endpoint population is described as 15 subjects randomized and completing Stage 1, and the arm summaries each show 15 participants. These counts do not establish whether all scheduled endpoint assessments were available for every participant or how incomplete measurements were handled. No imputation method, exclusion rule, or sensitivity analysis is described.

The record does not provide detailed analysis-population definitions, such as rules for inclusion in a safety or efficacy analysis beyond the stated Stage 1 completion population. It also does not report whether analyses followed an intention-to-treat principle or another population definition. Those labels should not be assigned based only on the randomized study description and the posted counts.

Finally, the primary endpoint covers assessments over time, but a detailed approach to combining or selecting those assessments is not reported. The registry description identifies approximate assessment timing through 240 minutes on Day 1, without specifying in the posted primary result whether the summary represents one time point, a maximum, or another time-based summary. Interpretation should be limited to the endpoint definition and mean values that are posted.

15. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 15 participants at risk for serious adverse events and zero participants affected. It lists 15 participants at risk for other adverse events and 15 affected. The group is labeled NS, LR, so the figures are recorded for the combined group label rather than separated into solution-specific counts. The registry record lists no serious adverse-event terms.

These figures describe what is recorded in the registry; they do not provide event-level detail for the other adverse events, their severity, timing, or relationship to either solution. The death count is not reported in the registry record. The figures should not be used to infer that no adverse events occurred: the posted record distinguishes zero participants with serious events from 15 with other adverse events.

The sample was 15 participants, and the safety summary is limited to the categories and groupings the registry reports. It does not establish the frequency of uncommon events or characterize safety in populations beyond the healthy volunteers studied. No treatment recommendation follows from these counts.

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

The posted results describe a Stage 1 comparison in which healthy volunteers received NS in one thigh and LR in the other, with Hylenex preceding both infusions. Mean discomfort ratings were 20.0 mm for NS and 9.4 mm for LR on the 0-to-100 mm VAS. The unadjusted re-calculated contrast was -10.6 mm for LR minus NS, with an interval from -24.1 to 2.896 and an unadjusted p-value of 0.124. These figures summarize the observed sample, with uncertainty that includes no mean difference.

They do not prove that the solutions are equivalent, that either solution is more comfortable in general, or that the observed mean difference is clinically important. The record gives no clinical threshold for interpreting the size of a VAS difference, and it does not report the primary analysis method or a sponsor-reported inferential result. With the within-participant design, separate group summaries also do not show the distribution of paired differences.

The results concern the specific Stage 1 procedure and population: healthy volunteers, 500 mL of each solution, opposite thighs, and 150 units of Hylenex before each infusion. The record does not support generalizing these findings to other populations, doses, routes, clinical settings, or protocols. It also does not answer the Stage 2 comparison of NS with buffered NS, because Stage 2 results are not reported in the registry record.

The secondary summaries add information about flow rate and thigh circumference, but their uncertainty and the absence of reported multiplicity procedures limit how strongly they can be used to reinforce a conclusion. Safety figures record zero participants with serious adverse events and 15 with other adverse events in the combined NS, LR group. They are descriptive registry counts and do not establish the absence of risk.

17. Why This Trial Matters Statistically

This trial is statistically interesting because the Stage 1 procedure gives each participant both solutions, one in each thigh. That structure creates paired observations: comparisons can use the within-person contrast, potentially accounting for some stable differences between participants. Yet the posted group means and standard deviations do not reveal the paired-difference distribution, and the primary analysis method is not reported. This makes the distinction between the study’s design description and the available summary statistics especially important.

The primary outcome is subjective and measured on a bounded VAS. A mean difference provides a compact summary, but it cannot alone describe the full distribution of ratings or establish whether the contrast matters to participants. The interval spans zero, while the record supplies no clinical interpretation threshold. The result is therefore a useful example of why effect size, precision, measurement context, and study design need to be considered together rather than relying on a p-value alone.

The small completed Stage 1 group also makes planning illustrations sensitive to the observed effect. The registry’s planning assumptions can show how smaller target effects imply larger sample requirements, but they do not recover the trial’s original design rationale. Separating that planning exercise from observed evidence prevents a retrospective calculation from being mistaken for the investigators’ original plan or for evidence about the study’s power.

Finally, the record illustrates the limits of registry summaries. It reports selected endpoint statistics and some secondary tests, but does not report a full statistical plan, missing-data procedures, primary test, confidence-interval level, or multiplicity handling. Those gaps are not evidence that procedures were absent; they mean the registry record does not document them. Careful interpretation distinguishes recorded results from analyses that cannot be verified from the record.

18. 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 limitation for interpretation is the small Stage 1 population: 15 subjects randomized and completing the stage. Estimates from a small group can be imprecise, and the confidence interval for the primary contrast spans zero and values in either direction. The record does not report participant-level data, so the distribution of paired discomfort differences and the influence of individual observations cannot be assessed.

The paired administration is central to the design, but the registry classifies the study model as parallel and does not describe the primary endpoint’s statistical method. Separate summaries for NS and LR do not provide the within-person covariance needed to reproduce a paired estimate from the posted means and standard deviations alone. The primary comparison shown is an unadjusted re-calculation from summary statistics, not a sponsor-reported primary analysis.

The endpoint description covers approximate assessments through 240 minutes on Day 1, but the registry record does not clarify which assessment or time-based summary produced the posted mean. It also does not report the primary interval’s confidence level or method, a clinical threshold for meaningful discomfort, or handling of missing measurements. Multiplicity procedures and detailed analysis-population definitions are not reported.

Only Stage 1 results are available for interpretation. Although Stage 2 was described as comparing NS with buffered NS, its results are not reported in the registry record. The outcomes available concern healthy volunteers under the specified infusion procedure, so generalization beyond that context is uncertain. The safety summary combines NS and LR, provides limited detail for other adverse events, and does not report the death count.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex) — NCT00656370.
• Registry record last updated 2018-10-17; status last verified 2018-09.
• Results first posted 2010-05-14.
• 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.

22. Record Summary

NCT00656370 is a completed Phase IV randomized study of subcutaneous hydration with Hylenex. The registry records enrollment of 15 healthy volunteers and describes Stage 1 as a comparison of NS and LR, with 150 units of Hylenex before each infusion. Each subject received 500 mL of each solution in opposite thighs.

The primary endpoint was participant-rated infusion-site discomfort on a 0-to-100 mm VAS. Mean values were 20.0 mm for NS and 9.4 mm for LR. The unadjusted re-calculated LR-minus-NS mean difference was -10.6 mm, with a confidence interval from -24.1 to 2.896 and an unadjusted p-value of 0.124. The primary analysis method is not reported in the registry record.

Secondary results include flow rate and thigh circumference, with reported Wilcoxon signed rank test p-values of 0.93 and 0.67, respectively. Safety counts list zero participants with serious adverse events and 15 with other adverse events in the combined NS, LR group. Stage 2 results, detailed missing-data procedures, multiplicity handling, and the original sample-size justification are not reported in the registry record.