Study to Evaluate the Safety of the Viscoelastic Substance PRO-149, Compared to Healon® EndoCoat.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety of the Viscoelastic Substance PRO-149, Compared to Healon® EndoCoat. (NCT04702802), a randomized na study. The primary outcome is Change in Corneal Endothelial Cell Count.

2. Clinical Question

3. Trial Design

This was a pilot, controlled, parallel-group, open, randomized clinical trial. The registry record lists the allocation as randomized, masking as none, and the model as parallel. It lists an enrollment of 36 participants. The posted results for the primary outcome include 18 participants in the PRO-149 arm and 18 in the Healon® EndoCoat arm.

The study evaluated the viscoelastic substances as devices used during phacoemulsification and intraocular lens implantation in patients with age-related cataract. Both products are described as sodium hyaluronate 3% in pre-filled syringes. Each was applied in the ocular anterior chamber to form the space needed for the procedure. The registry record lists the sponsor as Laboratorios Sophia S.A de C.V. and the phase as NA.

The record lists the study as completed, with a start date of 2021-09-07 and a primary completion date of 2021-10-29. These dates describe the registry entry and do not by themselves establish the timing of each participant's follow-up or the completeness of all outcome data. The primary outcome timeframe specifies an eligibility visit at Days -15 (±2) and a final visit at Days 29 (±2).

Five secondary outcomes are listed: participants presenting adverse events, central corneal thickness change, anterior chamber cellularity change, anterior chamber flare change, and best corrected visual acuity change. Eight outcome measures are listed in total. Detailed methods for random sequence generation, allocation concealment, implementation, and analysis populations are not reported in the registry record. The study is open, so masking is not listed.

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

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 Corneal Endothelial Cell Count, measured over Days: -15 (±2) (eligibility visit), and 29 (±2) (final visit).

The primary endpoint is change in corneal endothelial cell count, measured using specular microscopy and expressed in cells/mm2. The registry record identifies the outcome as a mean with standard deviation and gives the measurement occasions as the eligibility visit at Days -15 (±2) and the final visit at Days 29 (±2). The arm-level results are reported as mean changes, with negative values in both arms.

Corneal endothelial cells are relevant to the safety evaluation because the count is a measured feature of the cornea. The study's stated purpose is to evaluate the safety of PRO-149 when used as a device during cataract surgery, compared with Healon® EndoCoat. The registry description notes that normal density varies with age and gives an average range of 1500 - 3500 cells/mm2 for ages 40 to 90. That reference describes density, whereas the posted primary results describe change; they should not be treated as the same quantity.

The record does not state the precise calculation used to define change, such as the order of subtraction, nor does it give a clinically important threshold for interpreting a change. It also does not report how missing measurements were handled. The endpoint therefore supports a comparison of the posted group summaries, but the registry information alone does not define a threshold for judging the size or importance of the observed changes.

7. Results Posted in the Registry

• Arm 2; Healon® EndoCoat: mean -482.30 versus -441.33 on control; difference -40.97 (95% CI -338.42 to 256.48), standardized effect d = -0.09; z-test p = 0.787.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical measurement of endothelial cell count change. The registry record reports a mean and standard deviation for each arm. The mean describes the average recorded change within an arm. The standard deviation describes how dispersed individual measurements were around that arm's mean. These summaries answer different questions: the mean characterizes the group average, while the standard deviation describes variability among participants.

What does the mean difference represent?

The posted comparison is a difference between the arm means. Its estimate is -40.97 cells/mm2 for Healon® EndoCoat relative to PRO-149. A negative estimate in this comparison indicates that the Healon® EndoCoat mean change was lower than the PRO-149 mean change, using the comparison direction reflected in the posted arm values. The estimate is not an individual participant's change, nor does it describe how many participants had a particular response.

In general, a difference in means is useful when an outcome is measured on a numeric scale and the research question concerns average outcomes between groups. It does not show the full shape of the individual results. The standard deviations, 420.4 cells/mm2 for PRO-149 and 487.7 cells/mm2 for Healon® EndoCoat, give context for the within-arm spread. The record does not provide individual participant measurements or a distributional plot that would allow a fuller assessment of the outcome's shape.

How should the confidence interval be read?

A confidence interval describes the uncertainty around an estimated effect under the statistical method used. In general, it gives a range of values reasonably compatible with the observed data and the method's assumptions. The posted 95% confidence interval for the mean difference is -338.4 to 256.5 cells/mm2. Because the interval includes zero and values on either side, the data do not identify the direction of the mean difference precisely. A confidence interval is not a guarantee that the true value lies within its limits, and it is not a range containing a specified share of individual participant outcomes.

What does the p value add?

The unadjusted p value is 0.787. In general, a p value describes how unusual the data, or results more extreme than these, would be if the null hypothesis and the test assumptions were true. It does not measure the size or clinical importance of an effect, and it is not the probability that the null hypothesis is true. Here, the p value is consistent with the broad interval and does not indicate strong evidence against a zero mean difference. The registry record does not report whether any other inferential testing was prespecified.

Why does variability matter?

In general, greater outcome variability makes it harder to estimate a group mean difference precisely, all else being equal. The standard deviations are large relative to the point estimate, and each arm has 18 participants in the posted outcome results. That context helps explain why a modest estimated difference can coexist with a broad confidence interval. This is an interpretation of the posted summaries, not a reconstruction of the trial's design or its original statistical plan.

Over-dispersion is a concern when observed variation is greater than a statistical model expects. In general, failing to account for over-dispersion can make uncertainty estimates too small and statistical evidence appear stronger than it is. The registry record does not report a model-based analysis, a dispersion assessment, or evidence that over-dispersion was evaluated. The posted summary statistics alone do not establish whether that issue arose.

What details of the analysis are available?

The registry record identifies the primary outcome as a mean of a continuous measure with standard deviation. It posts arm-level summaries and a mean-difference estimate, confidence interval, and unadjusted p value. It does not report the named statistical test, any covariate adjustment, the exact method for calculating the interval, or the precise formula used to define change from the eligibility visit to the final visit. It also does not report the analysis population or how missing outcome measurements were treated.

Randomization can support a fair comparison by reducing systematic differences between assigned groups in expectation, but the registry record does not describe sequence generation or concealment. Open allocation means masking is listed as none; the record does not explain whether outcome measurement or analysis was independently masked. These reporting gaps limit how fully the analysis can be assessed. The posted comparison should therefore be understood as a summary of the registry results, rather than as a complete account of the statistical methods.

10. Confidence Intervals and Precision

The mean difference estimate is -40.97 cells/mm2, and its 95% confidence interval ranges from -338.4 to 256.5 cells/mm2. The interval is broad and spans zero, so the estimate does not pin down the direction of the difference. Values compatible with the interval include a lower mean change in the Healon® EndoCoat arm and a higher mean change. The interval also allows differences substantially larger in magnitude than the point estimate.

In general, a confidence interval communicates precision by showing how much uncertainty remains around an estimate. A narrow interval indicates greater precision than a wide interval, given the same measurement scale. It does not describe the spread of individual participant outcomes; the arm-level standard deviations do that. Here, the standard deviations are 420.4 cells/mm2 for PRO-149 and 487.7 cells/mm2 for Healon® EndoCoat, while the primary outcome results include 18 participants per arm.

The interval's inclusion of zero is consistent with the unadjusted p value of 0.787. Neither fact proves that the mean changes are equal. A nonsignificant comparison can reflect an effect near zero, substantial variability, limited information, or a combination of these. The registry record does not report a threshold defining a clinically important difference, so the interval cannot be classified against such a threshold from the posted information.

The confidence interval should be interpreted in the context of the stated outcome and follow-up timeframe: change in endothelial cell count between the eligibility and final visits. Details of the change calculation and the interval method are not reported in the registry record. These limitations counsel against treating the displayed limits as a complete account of every source of uncertainty.

11. 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 describe participants per arm, not total events. They are illustrations based on the observed mean difference and are not the original trial's sample-size justification. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial's own original design assumptions are not reported in the registry record.

The 80% power column represents the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the selected effect under those assumptions, if that effect were real. The 90% power column gives the corresponding number per arm for a 90% chance. These are prospective planning concepts, not descriptions of the probability that the completed trial found a true effect. They are not observed power.

The planning estimates are 1,939 participants per arm for 80% power and 2,596 for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, the corresponding estimates are 3,447 and 4,614 participants per arm. For 50% of the observed effect, they are 7,755 and 10,382 participants per arm. Smaller effects are harder to distinguish from random variation, so detecting them requires more participants under the same assumptions.

These figures are sensitive to the observed effect used as their starting point and to the stated calculation assumptions. They do not revise the trial's actual enrollment of 36, and they do not establish what enrollment would have been appropriate under a different effect, outcome model, or design. No time-to-event outcome is involved in these planning figures.

12. 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 = -40.970; pooled standard deviation σ = 455.295.
2. n = 2 × (1.96 + 0.842)² × 455.295² / -40.970² = 1,938.6, rounded up to 1,939 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 <- -40.97                      # observed difference in means
sigma <- 455.295206432047                     # 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(4702802)
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 = 1,939 (80% power), 2,596 (90% power)
 75% of observed effect: n per arm = 3,447 (80% power), 4,614 (90% power)
 50% of observed effect: n per arm = 7,755 (80% power), 10,382 (90% power)
power.t.test: 1939.6 
Simulated power at n = 1,939 per arm: 0.799 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists five secondary outcomes in addition to the primary outcome: participants presenting adverse events, change in central corneal thickness, change in anterior chamber cellularity, change in anterior chamber flare, and change in best corrected visual acuity. Eight outcome measures are listed in total. The record posts no analysis records, and it does not give detailed results for those secondary measures in the information summarized for this trial.

When a study examines multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. In general, methods for handling multiplicity may define a primary comparison, adjust significance thresholds, or specify a hierarchy of tests. The registry record does not report a multiplicity strategy, whether secondary outcomes were tested inferentially, or whether any analyses were planned as exploratory. The posted p value is identified as unadjusted; it should not be interpreted as accounting for tests of other outcomes.

The record does not report the analysis population for the primary outcome or explain whether participants were analyzed according to randomized assignment. It does not report missing-data counts, reasons for missing measurements, imputation methods, or sensitivity analyses. As a result, the impact of incomplete endpoint data cannot be assessed from the registry information. The posted outcome summaries include 18 participants in each arm, but the record does not explain whether this represents all randomized participants or a particular analysis set.

Other details that would support an assessment of the analysis are also not reported in the registry record: the prespecified statistical plan, handling of protocol deviations, covariate adjustment, and the exact method used to calculate change and its confidence interval. These absences do not establish that such methods were not used; they mean the registry record does not describe them. Interpretations should remain tied to the analyses and summaries that are actually posted.

14. 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 non-serious adverse event terms

The registry record lists 18 participants at risk for serious adverse events in each arm. It lists zero participants with serious adverse events in the PRO-149 arm and zero in the Healon® EndoCoat arm. Deaths are listed as zero in both arms. For other adverse events, 1 participant is listed in the PRO-149 arm and 2 participants in the Healon® EndoCoat arm, with 18 participants at risk in each.

These figures are participant counts, not a description of event severity or duration. The record does not report the types, timing, seriousness criteria, or relationship to treatment for the other adverse events. No serious adverse-event terms are listed, and specific event details are not reported in the registry record. A count of zero recorded serious events does not establish that a treatment is free of risk; it describes what was recorded in this trial.

The trial was a pilot with 18 participants per arm in the posted results. Small participant counts limit how much the safety figures can characterize uncommon events. The adverse-event counts should be read as a brief registry summary, not as a complete safety profile or a definitive comparison between the devices.

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

The posted primary results describe decreases in mean corneal endothelial cell count in both arms over the stated measurement period. The mean change was -441.3 cells/mm2 for PRO-149 and -482.3 cells/mm2 for Healon® EndoCoat. The estimated mean difference, -40.97 cells/mm2 for Healon® EndoCoat relative to PRO-149, is imprecise: its 95% confidence interval extends from -338.4 to 256.5 cells/mm2 and includes zero.

These data do not establish that the arms have the same mean change. Nor do they establish a clear difference in either direction. The result is compatible with a range of possible differences, and the registry record does not provide a clinically important threshold with which to judge that range. The unadjusted p value of 0.787 is not a measure of equivalence, and it does not mean there is a 78.7% probability that the observed difference is due to chance.

The results apply to the trial as recorded: a randomized, open, parallel-group pilot study of viscoelastic devices used during phacoemulsification and intraocular lens implantation in participants with age-related cataract. The primary outcome is a measured change in endothelial cell count between the eligibility and final visits. The results do not, by themselves, answer questions about outcomes beyond the recorded timeframe or establish findings for populations or procedures not described in the registry record.

The adverse-event summary lists no serious adverse events and no deaths in either arm, and other adverse events for 1 participant with PRO-149 and 2 with Healon® EndoCoat. Limited event detail and the small group sizes prevent these counts from serving as a comprehensive comparison of safety. Overall, the registry results should be read as descriptive evidence from a small pilot trial, with a broad interval around the primary comparison and limited detail about analysis and safety ascertainment.

16. Why This Trial Matters Statistically

This trial illustrates why a point estimate should be read together with its uncertainty. The primary comparison's estimate is -40.97 cells/mm2, but the confidence interval from -338.4 to 256.5 is wide and includes differences in either direction. Looking only at the point estimate would conceal the uncertainty; looking only at the p value would also miss the range of effects compatible with the data.

The design is explicitly described as a pilot, with 18 participants per arm in the primary results. Pilot studies can provide early information about procedures, measurements, and observed variability, but a small trial may leave a wide range of plausible group differences. The planning illustrations based on the observed effect show how strongly required enrollment depends on the effect size selected for planning. They are not a substitute for the trial's original design rationale, which is not reported in the registry record.

The study also highlights the distinction between a statistical comparison and a claim of equivalence. A confidence interval containing zero does not demonstrate that two devices produce the same result. A conclusion of equivalence would require a suitable framework and a prespecified margin; such information is not reported in the registry record.

Finally, transparent interpretation depends on more than the outcome values. The registry record identifies randomization and an open design, but does not describe sequence generation, missing-data handling, analysis populations, or multiplicity procedures. The posted summaries are informative, while those reporting gaps limit a fuller appraisal of the comparison. This is why the strength of a conclusion should match both the precision of the estimate and the detail available about how it was obtained.

17. 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 registry record characterizes the study as a pilot and reports 36 participants enrolled, with 18 participants per arm in the primary outcome results. The resulting comparison has a broad confidence interval, so the direction and size of the mean difference are not estimated precisely. The posted primary outcome is a change measure, but the exact calculation used to derive change is not reported in the registry record.

The study is listed as open, with masking set to none. The record does not explain whether cell-count measurement or statistical analysis was masked. It also does not report the randomization sequence method or allocation concealment. These details matter when assessing the potential for bias in a small randomized comparison.

The primary outcome timeframe is stated as Days -15 (±2) and 29 (±2), but the registry information does not describe adherence to visit windows, missing measurements, or the analysis population. There is no reported clinical threshold for a meaningful difference. The five listed secondary outcomes are not accompanied by detailed results in the information recorded here, and a multiplicity approach is not reported.

Safety results are brief participant counts. Specific types and characteristics of other adverse events, their timing, and their relationship to the devices are not reported in the registry record. The record lists zero serious adverse events and zero deaths in both arms, but a small pilot trial cannot characterize uncommon events precisely. These limitations do not invalidate the posted statistics; they define the scope of conclusions that can be drawn from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety of the Viscoelastic Substance PRO-149, Compared to Healon® EndoCoat. — NCT04702802.
• Registry record last updated 2025-12-16; status last verified 2025-12.
• Results first posted 2025-12-16.
• 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.

21. Record Summary

NCT04702802 is a completed, randomized, open, parallel-group pilot trial comparing PRO-149 with Healon® EndoCoat during phacoemulsification and intraocular lens implantation in patients with age-related cataract. Both devices are described as sodium hyaluronate 3%. The registry record lists 36 participants enrolled.

The primary outcome is change in corneal endothelial cell count, measured by specular microscopy between the eligibility and final visits. The posted mean changes were -441.3 cells/mm2 for PRO-149 and -482.3 cells/mm2 for Healon® EndoCoat. The reported mean difference was -40.97 cells/mm2, with a 95% confidence interval from -338.4 to 256.5 and an unadjusted p value of 0.787.

The safety summary lists no serious adverse events or deaths in either arm, and other adverse events for 1 participant with PRO-149 and 2 with Healon® EndoCoat. Further details about the analysis, missing data, and event characteristics are not reported in the registry record.