Acetazolamide Efficacy in Ataxia in PMM2-CDG: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acetazolamide Efficacy in Ataxia in PMM2-CDG (NCT04679389), a randomized phase 2, phase 3 study. The primary outcome is Efficacy of Acetazolamide on Ataxia Measured Via Miniature International Cooperative Ataxia Rating Scale (Mini-ICARS).

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group, placebo-controlled study with quadruple masking. The listed phases are phase 2 and phase 3. Mayo Clinic is named as the sponsor. The condition is PMM2-CDG, also listed as CDG1A, and the registry lists enrollment of 25.

The intervention was acetazolamide, given as a capsule or liquid suspension, and the comparator was a matching placebo in corresponding forms. The primary outcome compared change in Mini-ICARS score from baseline to six months. The study also listed safety objectives, PMM2-related biomarkers, other clinical measures, and exploration of characteristics of people who did not respond to acetazolamide.

The registry lists a start date of 2021-03-17 and a primary completion date of 2024-01-24. Its status is terminated. The record does not explain why the study was terminated, and it does not report whether the planned study duration or enrollment target changed. The secondary outcome timeframes include follow-up through study completion, approximately 2 years, while the primary comparison is at six months; the record does not establish that every participant completed that follow-up.

Original design details such as the planned sample-size justification, anticipated effect, and statistical analysis plan are not reported in the registry record. The degree of masking is recorded, but the record does not provide further details about who was masked or how masking was assessed.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Data was not collected nor analyzed for two subjects in the Acetazolamide arm and one subject in the Placebo arm

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 Efficacy of Acetazolamide on Ataxia Measured Via Miniature International Cooperative Ataxia Rating Scale (Mini-ICARS), measured over baseline-6 months.

The primary endpoint is the change in Mini-ICARS score from baseline to after six months of treatment, compared between the acetazolamide and placebo groups. Mini-ICARS is a scale for ataxia-related impairment. The registry describes a minimum score of 0 and a maximum of 100; higher scores indicate greater impairment. Its subscales use ordinal ratings, with 0 indicating normal and higher values indicating greater impairment or inability to complete a task.

A change score focuses on movement in the measured outcome during the stated period rather than on the score at a single time alone. Comparing the groups' mean changes is intended to assess whether the observed average change differed between treatment assignment groups. This is a continuous outcome, and the registry reports group means and standard deviations.

Mini-ICARS was selected as the primary measure for the stated objective of evaluating ataxia. The scale gives a numerical way to compare impairment over time, but a group mean does not describe every participant's experience or the full distribution of individual changes. The registry record does not report a threshold for a clinically meaningful change, and the posted result should therefore be read as a statistical comparison of mean change rather than as evidence about the meaning of any particular score change for an individual.

7. Results Posted in the Registry

• Acetazolamide: mean 1.64 versus 1.36 on control; difference 0.28 (95% CI -2.41 to 2.97), standardized effect d = 0.09; z-test p = 0.838.

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.

Abnormal Blood pH Value

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Acetazolamide: 0.0% (0/13) versus 8.3% (1/12) on control; risk difference -8.3 percentage points (95% CI -24.0 to 7.3); unadjusted two-proportion z-test p = 0.288.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Acetazolamide and the control. The interval gives the range of effects that remain compatible with the data.

Electrolyte Balance Testing

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Acetazolamide: 0.0% (0/13) versus 8.3% (1/12) on control; risk difference -8.3 percentage points (95% CI -24.0 to 7.3); unadjusted two-proportion z-test p = 0.288.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Acetazolamide and the control. The interval gives the range of effects that remain compatible with the data.

Change in Nijmegen Pediatric CDG Rating Scale (NPCRS)

• 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:
  • Acetazolamide: mean 1.20 versus 0.27 on control; difference 0.93 (95% CI -0.69 to 2.55), standardized effect d = 0.49; z-test p = 0.262.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Acetazolamide and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several kinds of information: laboratory and biomarker measures, patient-reported scores, dysarthria, and the Nijmegen Pediatric CDG Rating Scale. The posted numerical secondary results span binary participant counts and a continuous score. The registry also lists other secondary measures for which quantitative results are not reported in the registry record.

Across the posted secondary results, the estimates are uncertain and do not form a consistent basis for a strong conclusion that would override the primary comparison. The registry's listed analysis results include different test methods, and the secondary outcomes do not all measure the same domain or use the same scale. They should not be combined informally into a single summary of benefit or harm.

Secondary findings can help describe what was measured beyond the primary endpoint and can suggest questions for further evaluation. However, multiple outcomes create more opportunities for apparently notable results to arise by chance. The registry does not report whether a multiplicity adjustment was planned or whether these analyses were designated as exploratory. Unadjusted secondary p values therefore carry less weight than a prespecified, multiplicity-controlled primary analysis, especially when results are based on small groups.

The relationship to the primary result is contextual rather than confirmatory: these outcomes do not establish a different primary conclusion, and their varied content makes them difficult to interpret as a coherent replication of the Mini-ICARS comparison. The record does not report enough detail to determine how all secondary analyses were selected, prioritized, or interpreted in the original analysis plan.

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

• Abnormal Blood pH Value
• Electrolyte Balance Testing
• Urine Calcium Excretion Testing
• Examine Effect of Acetazolamide on PMM2 Biomarker Carbohydrate Deficient Transferrin
• Change in Patient Reported Outcomes Measurement Information System (PROMIS) Score
• Change in Dysarthria as Measured by the PATA Score
• Change in Nijmegen Pediatric CDG Rating Scale (NPCRS)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score, and the registry reports its mean and standard deviation in each group. The posted sponsor analysis used a two-sided t-test. A t-test assesses whether the observed difference between group means is unusual under a model in which the population means are equal, while accounting for variation within the groups. A two-sided test considers differences in either direction rather than specifying only one direction.

What the mean difference represents

The recalculated mean difference is acetazolamide minus placebo. It is based on the group means and the posted sample sizes. A positive estimate means the acetazolamide group's reported mean change is numerically higher; it does not by itself say whether this represents improvement or worsening, because the registry does not state the sign convention used for change. The registry's interpretation of the scale is that higher Mini-ICARS scores indicate greater impairment.

The recalculated comparison is unadjusted. It is a simple comparison of the posted summary statistics, not an adjusted estimate from a model accounting for other variables. No covariate-adjusted primary analysis is reported in the registry record. The recalculated estimate and its interval are useful for reading the posted data, but the registry's own analysis remains the sponsor-reported analysis.

What a p value tells the reader

A p value describes how compatible the observed data are with a specified null model, assuming the model's conditions. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The reported p value is 0.84; the unadjusted recalculation is 0.838. Both are consistent with the estimate and interval indicating that the observed data do not clearly distinguish the group means.

A p value above a conventional significance threshold does not demonstrate that there is no difference. Such a conclusion would require a design and analysis intended to establish equivalence or rule out a prespecified range of differences. The registry does not report an equivalence margin or a noninferiority objective. The p value should therefore be read alongside the estimated difference, its confidence interval, the endpoint counts, and the study's limitations.

Why variation matters

The standard deviation describes how spread out individual scores are around the group mean. It is not the same as the standard error, which describes uncertainty in an estimated mean. The posted standard deviations are 3.2 for acetazolamide and 3.23 for placebo. With modest endpoint counts, variation among participants contributes to uncertainty in the estimated group difference. A mean alone would conceal that variation.

The registry reports no evidence that the continuous primary outcome required a special model for over-dispersion. In general, over-dispersion matters when observed variability in data is greater than a model assumes, which can make uncertainty estimates too small if the mismatch is ignored. That general concern should not be taken as a claim that over-dispersion was present in this trial.

How to read the confidence interval

The 95% confidence interval for the recalculated mean difference is -2.407 to 2.967. In general, a confidence interval describes a range of values compatible with the data under the analysis assumptions and indicates the precision of the estimate. It is not a guarantee that the true effect lies within the particular interval, and it does not assign probabilities to individual values inside it. Here the interval includes zero and extends to differences on both sides, so the point estimate is imprecise relative to the range of values compatible with the data.

The registry's reported analysis gives a p value but does not report its own mean-difference estimate or confidence interval. The interval discussed for the primary endpoint is therefore the unadjusted recalculation from posted summary statistics, not an interval attributed to the sponsor's analysis.

What the reported method cannot establish

The record does not report the full statistical analysis plan, the original sample-size justification, interim analyses, or a detailed analysis population definition. It also does not describe assumptions used for the sponsor's t-test beyond identifying it as two-sided. Without these details, the test can be described, but its relationship to any prespecified protocol choices cannot be fully assessed. The registry's termination status adds context, but the reason for termination and its implications for the analysis are not reported.

11. Confidence Intervals and Precision

The primary mean-difference estimate is 0.28, and its recalculated 95% confidence interval is -2.407 to 2.967. This interval is broad relative to the point estimate and crosses zero. In practical statistical terms, the posted data do not pin down the direction or size of the group difference precisely. The interval includes no difference as well as nonzero values on either side.

A confidence interval is an uncertainty summary, not a range of individual participant outcomes. It describes the precision of an estimated group contrast under the assumptions of the calculation. It does not mean that every value in the interval is equally plausible, nor does it establish that a particular value is clinically important. The registry does not report a clinically meaningful difference threshold for Mini-ICARS, so the interval cannot be judged against such a threshold using the record alone.

The endpoint counts are 11 in each group, and the registry states that data were not collected or analyzed for two participants in the acetazolamide arm and one in the placebo arm. The record does not explain the missing data or their handling. These omissions matter because the interval captures sampling uncertainty under the calculation, but does not account for possible bias from missing outcomes or from analysis choices that are not described.

The sponsor-reported analysis provides a two-sided p value of 0.84 but no sponsor-reported estimate or confidence interval. The recalculated interval is therefore a complementary precision summary based on posted group statistics, not a sponsor-reported interval.

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 own design assumptions. The trial's original sample-size justification and design assumptions are not reported in the registry record. The illustrations assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each row considers an effect equal to the stated fraction of the observed effect.

The figures are participants per arm for 80% power and participants per arm for 90% power. In plain language, the 80% column gives the modeled number of participants in each group for an 80% chance of detecting the assumed effect under the illustration's assumptions, if that effect were present. The 90% column uses a higher target probability of detection, and therefore requires more participants for the same assumed effect. These are planning quantities, not a report of how many participants were enrolled or analyzed.

Rows based on a smaller fraction of the observed effect call for more participants, because a smaller group difference is harder to distinguish from random variation. The figures should not be read as a recommendation for a future study without considering its objectives, endpoint, analysis plan, and relevant design assumptions. The registry's own trial design justification remains not reported in the registry record. These figures are not observed power.

For this continuous endpoint, the figures represent participants per arm, not total events. In time-to-event settings, a planning table may instead report total events; that distinction is not applicable to these continuous-outcome figures. The assumptions listed with the illustrations include equal allocation and normal approximation, but do not establish that the original trial used those assumptions.

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 = 0.280; pooled standard deviation σ = 3.215.
2. n = 2 × (1.96 + 0.842)² × 3.215² / 0.280² = 2,069.6, rounded up to 2,070 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 <- 0.28                      # observed difference in means
sigma <- 3.21503499203352                     # 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(4679389)
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 = 2,070 (80% power), 2,771 (90% power)
 75% of observed effect: n per arm = 3,680 (80% power), 4,926 (90% power)
 50% of observed effect: n per arm = 8,279 (80% power), 11,083 (90% power)
power.t.test: 2070.6 
Simulated power at n = 2,070 per arm: 0.804 (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-reported primary analysis is a two-sided t-test with p = 0.84. The recalculation from the posted group summaries gives an unadjusted p value of 0.838, which is consistent with the reported p value at its displayed precision. The registry does not flag a discrepancy between the two.

The recalculation also gives a mean difference of 0.28 and a 95% confidence interval from -2.407 to 2.967. The registry's reported analysis does not include its own estimate or confidence interval, so those values should be identified as recalculated rather than attributed to the sponsor. The recalculation is a simple, unadjusted comparison based on the posted summaries, while the sponsor analysis is the analysis identified in the registry record.

The agreement between the p values supports the reading that both analyses indicate no statistically clear group difference in this comparison. The sponsor's analysis takes precedence if a discrepancy is present; no such discrepancy is flagged in this record. Neither p value establishes that the groups are equivalent or that all potentially meaningful differences have been excluded.

15. Multiplicity, Missing Data and Analysis Populations

The study lists multiple secondary outcomes in addition to its primary Mini-ICARS outcome. Multiple testing raises the chance that at least one result will appear unusual by chance when many hypotheses are examined. A prespecified multiplicity strategy can control that risk, for example by adjusting the testing procedure or identifying a hierarchy of outcomes. Whether such a strategy was planned or applied is not reported in the registry record. The displayed secondary p values should therefore be treated as unadjusted unless the record states otherwise.

The primary endpoint analysis is reported as a two-sided t-test. The registry does not report a complete statistical analysis plan, including details about the intended handling of multiple outcomes, analysis populations, or other model choices. It also does not report interim analyses. No assumptions about these procedures can be inferred from the posted results alone.

For the primary endpoint, data were not collected or analyzed for two participants in the acetazolamide arm and one participant in the placebo arm. The reason for missing data, timing of missingness, and method for handling it are not reported in the registry record. The record does not state whether analyses followed an intention-to-treat population, a per-protocol population, or another definition. The primary endpoint counts of 11 in each group describe the reported outcome data; they do not by themselves define the analysis population for every outcome.

Missing outcomes can affect precision and, depending on why they are missing, can also affect the estimated comparison. The reported confidence interval reflects the recalculation from the available summaries, not an adjustment for unreported missing-data mechanisms. The registry status is terminated, but the reason and any relationship to outcome availability or analysis decisions are not reported. These reporting gaps limit assessment of how robust the findings are to analysis choices.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (8.3%), sepsis (8.3%), thromboembolic event (8.3%), acute kidney injury (8.3%), dehydration (7.7%).

The registry reports serious adverse events among 1 of 13 participants at risk in the acetazolamide group and 3 of 12 participants at risk in the placebo group. It reports no deaths in either group. Other adverse events were reported for 9 of 13 participants at risk in the acetazolamide group and 8 of 12 in the placebo group.

These are participant counts over the period recorded, not estimates of comparative risk adjusted for follow-up time or other factors. The registry lists serious adverse event terms with percentages, including Fever at 8.3%, Sepsis at 8.3%, Thromboembolic Event at 8.3%, Acute Kidney Injury at 8.3%, and Dehydration at 7.7%. The record does not provide enough detail to determine whether listed terms occurred in distinct participants or how each was attributed.

These figures describe reported events; they do not establish that an event was caused by a study treatment. The registry record does not report detailed event timing, duration, severity beyond the serious classification, or the sponsor's assessment of relatedness for each event. Small group counts also mean that the observed counts should not be treated as precise comparisons of safety between groups.

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

The primary result describes the difference in average Mini-ICARS change between the two randomized groups over the stated six-month period. The estimated mean difference is 0.28, with a recalculated 95% confidence interval from -2.407 to 2.967. The sponsor-reported two-sided test has p = 0.84. Together, these statistics indicate that the posted primary comparison does not clearly distinguish the group means.

This finding does not prove that the groups are identical. The interval includes zero and a range of differences in either direction, and the registry does not report an equivalence margin that would allow a formal conclusion of equivalence. The data also do not establish that every individual participant experienced the same outcome as the group average. A mean summarizes a group and cannot represent the range of individual results.

The result should not be translated into a claim about clinical improvement or worsening without knowing the sign convention used for change. Although the registry states that higher Mini-ICARS scores indicate greater impairment, it does not specify whether a positive change value means the score increased or decreased. It also does not report a threshold for a clinically meaningful change on the scale.

The available endpoint counts are limited, and three participants lacked primary outcome data. The record does not explain why those data were unavailable or how missingness was handled. The study is listed as terminated, but the reason is not reported. These registry entries constrain how confidently the primary estimate can be generalized or interpreted beyond the analyzed outcomes.

Secondary outcomes and adverse event counts offer additional descriptive information, but they do not replace the primary comparison. Some listed secondary measures have no quantitative results reported in the registry record, and the multiplicity approach is not reported. The posted results are therefore a record of the analyses and event counts described, not a complete account of all possible outcomes or an answer to every question about treatment effect and safety.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate and a significance test are not enough to characterize a clinical comparison. The primary mean difference is close to zero in the posted scale units, but its confidence interval spans values on both sides of zero. The interval makes the uncertainty visible and prevents a nonsignificant p value from being mistaken for proof of no effect.

The design also highlights the importance of knowing which participants contributed outcome data. The trial lists enrollment of 25, while the primary endpoint has 11 reported observations in each arm and three participants without collected or analyzed primary outcome data. The record does not explain the missing outcomes or define the analysis population. Those details are important for judging representativeness and potential bias, in addition to the precision calculation.

Multiple secondary outcomes can broaden the clinical picture, but they also increase interpretive complexity. Without a reported multiplicity strategy, isolated secondary findings require caution. In addition, the listed outcome domains vary, so they cannot be treated as interchangeable evidence about the primary ataxia question.

Finally, registry status and analysis completeness matter. The record identifies the study as terminated but does not report the reason. It also omits the original sample-size justification and full statistical plan. Those absences do not invalidate the posted statistics, but they limit what can be concluded about the intended design, the handling of outcomes, and the context in which the results were generated.

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 limitations are specific to the record and the posted results. First, the primary endpoint is based on 11 participants in each group, and the registry states that primary outcome data were not collected or analyzed for two participants assigned to acetazolamide and one assigned to placebo. Reasons for missing data and methods for handling them are not reported, leaving uncertainty about both representativeness and potential bias.

Second, the study is marked terminated, but the reason for termination is not reported in the registry record. The listed enrollment is 25, but the record does not explain how termination affected recruitment, follow-up, or analysis. The original sample-size justification is also not reported, so the observed endpoint counts cannot be evaluated against a documented target.

Third, the registry does not report a clinically meaningful Mini-ICARS difference or a sign convention for the change score. This limits interpretation of the clinical importance and direction of the group contrast, even though the scale's higher-score interpretation is stated. The sponsor-reported analysis provides a p value but not its own estimate or confidence interval; the interval in the statistical summary is recalculated from posted statistics.

Fourth, the full analysis plan, multiplicity approach, interim analyses, and analysis population definitions are not reported. Several listed secondary outcomes do not have quantitative results in the registry record. Safety information is presented as counts and listed terms, without detailed timing or event-level attribution. These limitations mean the posted results can be described, but a fuller assessment of robustness, clinical importance, and completeness is not possible from the record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Acetazolamide Efficacy in Ataxia in PMM2-CDG — NCT04679389.
• Registry record last updated 2025-03-20; status last verified 2025-03.
• Results first posted 2025-03-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry record describes a randomized, quadruple-masked, parallel, placebo-controlled phase 2 and phase 3 study of acetazolamide for ataxia in PMM2-CDG. Enrollment is listed as 25, the sponsor is Mayo Clinic, and the study status is terminated.

The primary outcome is change in Mini-ICARS score from baseline to six months. The reported group means are 1.64 for acetazolamide and 1.36 for placebo. The unadjusted recalculated mean difference is 0.28, with a 95% confidence interval from -2.407 to 2.967; the registry reports a two-sided t-test p value of 0.84.

The registry lists additional biomarker, clinical, and safety outcomes. It does not report the reason for termination, the original sample-size justification, full statistical plan, missing-data handling, or multiplicity strategy. Primary outcome data were not collected or analyzed for two acetazolamide participants and one placebo participant.