Efficacy in iNPH Shunting (PENS) Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy in iNPH Shunting (PENS) Trial (NCT05081128), a randomized na study. The primary outcome is Change in Gait Velocity.

2. Clinical Question

3. Trial Design

The PENS trial is described as a multicenter, blinded, randomized, placebo-controlled investigation of CSF shunt surgery for iNPH. The registry lists randomized allocation, double masking, and a parallel-group model. Its status is completed. The listed enrollment is 99, with a start date of 2022-05-18 and primary completion date of 2026-02-24.

Participants were assigned to an open-shunt group or a closed-shunt placebo group. Both groups received the programmable Certas Plus valve with Siphonguard at implantation. The groups differed in valve setting: the open-shunt group began at the active setting, while the placebo group began at the closed setting. The registry says the placebo group’s valve was set to active three months after the procedure. Thus, the randomized contrast for the primary endpoint is between the active and placebo settings during the period assessed at three months.

The primary outcome was change in gait velocity from baseline to three months. The registry also lists changes in cognition, bladder control, and balance and gait as secondary outcomes. The posted primary analysis includes 49 participants in each group; the registry notes that one randomized participant in the placebo group died at the three-month time point and was excluded from that analysis. The registry’s adverse-event counts use 49 participants at risk in the open-shunt group and 50 in the placebo group.

The registry record does not report further details about the randomization procedure, the masking roles, or the protocol’s original sample-size justification. Those details should not be inferred from the allocation and masking labels 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.

3 Months Post-Op

Reasons for not completing this period:

12 Months Active Shunting

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One participant in the placebo group who underwent randomization was deceased at the 3-month time point and is not included in this analysis.

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 Change in Gait Velocity, measured over Baseline and 3 months.

The primary endpoint is change in gait velocity, measured in meters per second, from baseline to three months. Gait velocity is a continuous measure: each participant’s result is represented on a numerical scale, and the group summaries are means with standard deviations. The endpoint description specifies a comparison of the change from baseline between participants assigned to active and placebo-controlled shunt settings.

As a general statistical consideration, a continuous measure can retain information about the size of changes across participants rather than reducing outcomes to categories such as improved or not improved. A group comparison of mean change estimates the average difference between groups over the specified interval. It does not indicate that every participant changed by the group average, and it does not describe the spread of individual responses by itself; the standard deviation helps describe that spread.

The registry identifies gait velocity as the primary endpoint for evaluating the shunt comparison. It also identifies cognition, bladder control, and balance and gait measures as secondary outcomes. The rationale for selecting gait velocity over other outcomes is not reported in the registry record, so no additional rationale should be attributed to the trial.

7. Results Posted in the Registry

• Open Shunt: mean 0.23 versus 0.03 on control; difference 0.20 (95% CI 0.11 to 0.29), standardized effect d = 0.87; z-test p = <0.001.

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.

Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA)

• 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:
  • Open Shunt: mean 1.30 versus 0.30 on control; difference 1.00 (95% CI -0.00 to 2.00), standardized effect d = 0.39; z-test p = 0.051.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Open Shunt and the control. The interval gives the range of effects that remain compatible with the data.

Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form

• 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:
  • Open Shunt: mean -3.30 versus -1.50 on control; difference -1.80 (95% CI -4.31 to 0.71), standardized effect d = -0.28; z-test p = 0.161.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Open Shunt and the control. The interval gives the range of effects that remain compatible with the data.

Change in Balance and Gait as Assessed by the Tinetti Score

• 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:
  • Open Shunt: mean 2.90 versus 0.50 on control; difference 2.40 (95% CI 0.57 to 4.23), standardized effect d = 0.52; z-test p = 0.010.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Open Shunt than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the posted secondary outcomes, the broad pattern is not uniform. The sponsor’s adjusted analyses show clearer evidence of a group difference for some measures, while another outcome has an interval that includes zero. The direction and strength of evidence therefore vary across cognition, bladder control, and balance and gait rather than forming a consistent result across every secondary measure.

This overall pattern can be considered alongside the primary gait-velocity result, but the secondary outcomes do not replace it. The primary endpoint addresses the trial’s designated main comparison. Secondary outcomes can provide supporting context about other measured domains, but they generally carry less confirmatory weight when many outcomes are examined and the registry does not report a multiplicity adjustment or a prespecified testing hierarchy.

Unadjusted secondary p-values are especially vulnerable to over-interpretation when several comparisons are made. In general, multiple testing increases the chance that at least one result may appear unusual by chance alone. A p-value for an individual secondary outcome does not account for that family of comparisons unless an adjustment is used. Whether such an adjustment was planned or performed is not reported in the registry record.

The most cautious reading is to treat the secondary findings as a set of related, supportive analyses whose estimates and uncertainty can guide further questions. They should not be combined into a single conclusion about overall efficacy without a reported analysis plan that defines how those outcomes relate to one another.

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

• Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA)
• Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form
• Change in Balance and Gait as Assessed by the Tinetti Score

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry summarizes it with group means and standard deviations. A mean gives the average observed change in each group. A standard deviation describes variation among participants around that group mean; it is not the uncertainty in the estimated mean difference. The primary comparison is the difference between the groups’ average changes.

What does the unadjusted comparison estimate?

The unadjusted mean difference compares the reported mean change in the open-shunt group with the reported mean change in the placebo group. In the posted recalculation, the difference is 0.2 m/s. The confidence interval around that estimate reflects sampling uncertainty under the assumptions used for the simple comparison. It does not account for unreported sources of uncertainty, and it is not a range containing a stated proportion of individual participants’ outcomes.

The unadjusted p-value assesses how compatible the observed comparison is with a null model of no group difference, under the test’s assumptions. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of the estimate. A small p-value can coexist with uncertainty about the estimate’s practical meaning or its applicability outside the analyzed participants.

Why is there also a regression result?

The registry reports a linear regression analysis with a treatment coefficient in an adjusted model. In general, regression estimates a group contrast while accounting for variables included in the model. The coefficient is the reported treatment contrast after that adjustment. The registry record does not identify which variables were included, how they were selected, or how missing values were handled in the model. It is therefore possible to state the adjusted estimate and its uncertainty, but not to reconstruct the model specification from the registry information.

The adjusted and unadjusted estimates answer closely related but not identical statistical questions: one is based on the group summaries alone, while the other comes from the sponsor’s regression model. They should not be treated as independent replications. Here the adjusted primary estimate and the unadjusted recalculation are both positive and are reported with confidence intervals that exclude zero.

What does the confidence interval contribute?

A confidence interval gives a range of estimates compatible with the data and the method used, at the stated confidence level. In repeated use of the same procedure under its assumptions, intervals constructed this way would cover the underlying parameter at the stated rate. For an individual trial, the interval communicates precision: narrower intervals indicate less sampling uncertainty than wider ones. It does not account for possible bias from design, measurement, missing data, or analysis choices.

For the primary endpoint, the unadjusted interval is entirely on the positive side of zero. The sponsor’s adjusted interval is also entirely positive. This makes the direction of the average group contrast clearer than would an interval spanning zero, while still leaving uncertainty about the exact size of the contrast. Statistical compatibility with a nonzero difference does not by itself establish clinical importance.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model assumes. When a model understates variability, standard errors may be too small and confidence intervals too narrow; p-values may then appear more decisive than the data warrant. This concern is particularly relevant when a statistical model assumes a specific variance structure that does not fit the observations. The registry lists standard deviations for the continuous outcomes, but it does not report an over-dispersion assessment or a variance-model diagnostic. No claim about whether over-dispersion occurred in this trial can be made from the registry record.

How should secondary comparisons be treated?

The secondary outcomes are also continuous measures summarized as mean changes and analyzed with linear regression in the sponsor’s reported results. Their estimates and intervals should be interpreted outcome by outcome, with attention to uncertainty and to the number of comparisons being considered. If many hypotheses are tested, the chance of at least one apparently notable result can increase. General approaches to multiplicity include adjusting significance thresholds or defining a testing hierarchy in advance; whether either approach was used in this trial is not reported in the registry record.

The registry reports the sponsor’s adjusted estimates for the primary and posted secondary outcomes, as well as unadjusted recalculations from summary statistics. These recalculations do not reproduce the adjusted model. They are useful as transparent descriptive comparisons, but the sponsor’s own model is the relevant posted adjusted analysis. The registry record does not report interim analyses, model diagnostics, or a full statistical analysis plan.

11. Confidence Intervals and Precision

Precision is reflected in the width of an estimate’s confidence interval. For the primary unadjusted comparison, the estimated mean difference is 0.2 m/s, with a 95% confidence interval from 0.109 to 0.291. The sponsor-reported adjusted estimate is 0.21, with a 95% confidence interval from 0.12 to 0.31. Both intervals lie above zero, so the reported analyses are consistent with a positive average difference between the randomized groups at three months.

The endpoints of a confidence interval are not guaranteed limits on the true value, and the interval is not a statement about the range of individual participant outcomes. It quantifies sampling uncertainty under the analysis method and its assumptions. It does not capture all possible uncertainty, including bias from missing outcomes, measurement, or model choices. The registry record notes a death and exclusion from the primary analysis, but does not provide enough detail to assess the impact of other missing data.

The sponsor’s adjusted interval and the unadjusted recalculation are similar in direction and scale, but they arise from different analyses. The adjusted model’s covariates are not reported in the registry record, so its precision cannot be independently reproduced from the posted group summaries alone. The unadjusted interval is a simple comparison based on those summaries; it should not be mistaken for the adjusted model’s uncertainty estimate.

For secondary outcomes, the intervals differ in how clearly they distinguish the estimates from zero. This variation is one reason not to rely on p-values alone. Confidence intervals make the range of estimates compatible with each analysis visible, while also reminding readers that a statistically distinguishable difference is not automatically important in practice. The registry record does not report a threshold for a clinically meaningful difference in gait velocity.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. They give participants per arm for the continuous outcomes; they are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each scenario considers detecting the stated fraction of the observed effect. The original sample-size justification and assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if the effect and model assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. These are design calculations, not probabilities that the observed result is true and not estimates of the chance that this completed trial would produce a significant result.

The rows that use a smaller fraction of the observed effect require more participants per arm. That pattern is expected in general: a smaller difference is harder to distinguish from random variation when other assumptions remain the same. The calculations use the observed effect as their starting point, so they are sensitive to how large that estimate happens to be. If the observed effect is unusually large or small relative to the underlying effect, the resulting illustration may not represent a future study’s needs.

This is not observed power. It is a forward-looking planning illustration that applies stated assumptions to the posted effect estimate. The registry record does not report whether these calculations were used to plan the trial.

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 = 0.200; pooled standard deviation σ = 0.230.
2. n = 2 × (1.96 + 0.842)² × 0.230² / 0.200² = 20.8, rounded up to 21 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 <- 0.2                      # observed difference in means
sigma <- 0.23                     # 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(5081128)
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 = 21 (80% power), 28 (90% power)
 75% of observed effect: n per arm = 37 (80% power), 50 (90% power)
 50% of observed effect: n per arm = 84 (80% power), 112 (90% power)
power.t.test: 21.8 
Simulated power at n = 21 per arm: 0.791 (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. Analyses Reported by the Sponsor

The sponsor’s primary analysis is a linear regression treatment coefficient from an adjusted model: 0.21, with a 95% confidence interval from 0.12 to 0.31 and p < 0.001. The recalculated unadjusted mean difference from the posted group summaries is 0.2 m/s, with a 95% confidence interval from 0.109 to 0.291 and an unadjusted p-value of <0.001. Both estimates point in the same direction, and both intervals exclude zero.

The recalculation is not a substitute for the sponsor’s analysis. It does not adjust for any model variables and cannot reproduce the adjusted regression without information about the model specification and participant-level data. The registry record does not report the adjustment variables. The sponsor’s result should therefore be used when describing the trial’s posted adjusted analysis; the simple recalculation is a separate, transparent comparison based on the group summaries.

The close agreement in direction and general scale offers a useful consistency check, but it does not show that the analyses are identical or independent. The registry record does not report a discrepancy between them.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcome measures, including the primary gait-velocity endpoint and secondary measures of cognition, bladder control, and balance and gait. Considering multiple outcomes creates a multiplicity issue: even if there were no true differences on any outcome, testing many comparisons can increase the chance of at least one apparently notable result. This is a general statistical concern, not evidence that a particular posted result is false.

The registry record does not report whether the secondary outcomes were adjusted for multiplicity, whether a hierarchy of tests was prespecified, or whether one secondary measure was intended to be confirmatory. Without that information, the posted secondary p-values should be interpreted individually and cautiously, rather than as a family of tests with a controlled overall error rate. The registry record also does not report a full statistical analysis plan.

Missing data and analysis populations are another limitation. The primary outcome description states that one randomized placebo-group participant died at the three-month time point and was not included in that analysis. The primary summaries contain 49 participants in each group, while the adverse-event summaries list 49 at risk in the open-shunt group and 50 in the placebo group. These are the reported counts for different analyses and should not be assumed to represent identical populations.

The registry record does not describe how other missing measurements were handled, whether any participants were excluded for reasons beyond the stated death, or whether the primary analysis followed an intention-to-treat approach. It also does not report sensitivity analyses for missing outcomes or the assumptions used in any missing-data model. Those omissions limit assessment of how robust the estimates are to incomplete follow-up. The presence of a stated exclusion does not, on its own, establish the direction or size of any resulting bias.

The randomized design supports a group comparison, but conclusions about its reliability also depend on how outcomes were collected and analyzed. Further details about masking, adherence, protocol deviations, and analysis populations are not reported in the registry record.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: subdural haematoma (8.2%), subdural hygroma (4.1%), sinus node disfunction (2.0%), supraventricular tachycardia (2.0%), vertigo (2.0%).

The registry reports serious adverse events for 18 of 49 participants at risk in the open-shunt group and 16 of 50 at risk in the placebo group. Other adverse events are reported for 39 of 49 and 40 of 50 participants, respectively. The recorded deaths are 0 in the open-shunt group and 3 in the placebo group. These are descriptive participant counts from the registry record; they do not establish that the assigned setting caused or prevented an event.

The registry lists subdural haematoma at 8.2% and subdural hygroma at 4.1% among the leading serious-event terms, followed by several terms at 2.0%. The figures are not a substitute for examining event definitions, timing, severity, relatedness, and recurrence. Those details are not fully reported in the summary data. A participant-level count of affected participants is also different from a count of every event, since one participant may experience more than one event.

The group counts should be read in light of the reported at-risk denominators and the trial’s limited follow-up for the primary comparison. The registry record does not provide enough information to draw a comparative safety conclusion or to explain the difference in deaths.

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

The primary result describes a difference in average change in gait velocity between the randomized groups at three months. The posted summaries and sponsor-reported adjusted model both give a positive estimate, with confidence intervals that do not include zero. Statistically, this is evidence of a between-group difference in the measured endpoint under the reported analyses.

That finding does not mean that every participant’s gait velocity increased, that all participants experienced the same change, or that the estimate predicts an individual outcome. Group means summarize averages, while individual responses may vary. Nor does a statistically distinguishable difference by itself establish how important the difference is to participants. A threshold for a clinically meaningful change is not reported in the registry record.

The result is specific to the comparison of valve settings and the three-month assessment described in the record. It does not establish whether differences persist after three months or how outcomes change over longer follow-up. The registry describes switching the placebo group to the active setting three months after the procedure, but the primary result does not answer what happens after that change.

The secondary results address additional measures, and their overall pattern is mixed. They provide context but do not independently settle the primary question, especially because multiplicity handling is not reported. The adverse-event counts are likewise descriptive and should not be interpreted as proof of a causal safety difference between groups.

In general, statistical evidence is one part of evaluating a clinical trial. Interpretation also depends on the endpoint’s practical meaning, the completeness and conduct of follow-up, the analysis population, and the applicability of participants and procedures to other settings. Several of these details are not reported in the registry record. The posted statistics should therefore be read as evidence about the specified randomized comparison and measured time point, not as a complete account of all possible outcomes.

18. Why This Trial Matters Statistically

This trial is statistically notable for using a randomized, blinded, placebo-controlled comparison of an active versus closed programmable shunt setting, with a continuous primary endpoint measured at a defined follow-up time. The design makes the between-group contrast more informative than a simple before-and-after comparison in one group, because the randomized groups provide a concurrent comparison under the trial conditions.

The distinction between the unadjusted recalculation and the sponsor’s adjusted regression result is also important. Both point in the same direction for the primary outcome, but they use different methods and the adjusted model’s covariates are not reported. Seeing both estimates encourages a reader to distinguish a transparent summary-statistic comparison from a model-based analysis rather than treating them as interchangeable.

The trial also illustrates why endpoint selection and multiplicity matter. Gait velocity is the designated primary outcome, while cognition, bladder control, and balance and gait are secondary measures. The secondary outcomes broaden the set of questions but also call for caution when interpreting individual p-values, particularly when the registry does not state whether multiplicity was addressed.

Finally, the registry’s note about a death and exclusion from the primary analysis highlights that the analysis population and missing outcomes matter even in a randomized trial. Randomization does not eliminate the need to understand who contributed data to each result. Clear reporting of analysis populations, missing-data handling, and model specifications would help readers judge precision and robustness more fully.

19. 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.

Several details needed for a fuller assessment are not reported in the registry record. These include the trial’s original sample-size justification, the randomization procedures, which roles were masked, and the full statistical analysis plan. The registry identifies double masking but does not specify its implementation. The regression covariates and model diagnostics are also not listed, limiting independent assessment of the adjusted estimates.

The primary analysis excludes one randomized participant in the placebo group who died at the three-month time point. The registry does not describe handling of any other missing measurements, provide a complete account of the analysis population, or report sensitivity analyses. This limits assessment of the influence of missing data and exclusions. The record also does not state whether the primary analysis was intention-to-treat.

The primary endpoint is assessed at baseline and three months. The posted primary result therefore does not establish the persistence of the group difference after that time. Although the registry describes a later active setting for the placebo group, it does not provide a longer-term comparison in the registry record reported for these results.

Multiplicity handling for the secondary outcomes is not reported. The secondary results should consequently be viewed with caution rather than treated as a set of independently confirmatory findings. The registry record also does not report a threshold for a clinically meaningful change in gait velocity, making it difficult to connect statistical precision directly to practical importance.

Finally, the adverse-event summaries provide participant counts and selected serious-event terms but do not supply full detail about timing, relatedness, recurrence, or event-level severity. Those summaries support description of reported events, not a comprehensive comparative safety assessment.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy in iNPH Shunting (PENS) Trial — NCT05081128.
• Registry record last updated 2026-08-27; status last verified 2026-08.
• Results first posted 2026-08-27.
• 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.

23. Record Summary

The PENS trial is a completed, randomized, double-masked, parallel-group, placebo-controlled study of CSF shunting in iNPH, with listed enrollment of 99. The primary endpoint was mean change in gait velocity from baseline to three months. The posted unadjusted comparison and sponsor-reported adjusted regression both show a positive between-group estimate, with confidence intervals excluding zero.

The primary analysis includes 49 participants in each group and excludes one placebo-group participant who died by the three-month time point. Secondary measures cover cognition, bladder control, and balance and gait; their overall pattern is mixed, and multiplicity handling is not reported. The registry also provides descriptive adverse-event counts. Details about the original sample-size justification, full analysis plan, model covariates, and handling of other missing data are not reported in the registry record.