Study of Rhopressa® for the Reduction of Elevated Intraocular Pressure in Patients With Glaucoma or Ocular Hypertension in a Real-world Setting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Rhopressa® for the Reduction of Elevated Intraocular Pressure in Patients With Glaucoma or Ocular Hypertension in a Real-world Setting (NCT03808688), a na phase 4 study. The primary outcome is Intraocular Pressure (IOP).

2. Clinical Question

3. Trial Design

This completed Phase 4 study assessed netarsudil ophthalmic solution 0.02% in a real-world setting among people with elevated IOP due to open-angle glaucoma or ocular hypertension. It was multicenter and open-label. The registry lists a single-group model, no allocation, and no masking. Participants received treatment for 12 weeks, either as monotherapy or concomitantly with other IOP-lowering agents.

The registry reports enrollment of 261. That figure is not necessarily the number included in the primary analysis. The mITT population required at least 1 dose of study medication and at least 1 follow-up visit with a completed IOP measurement; the number meeting these criteria is not reported in the registry record. The registry also does not report how many participants received monotherapy or concomitant therapy in the endpoint analysis. Safety group counts are reported separately.

The primary outcome was mean percent change from baseline IOP at Week 12, measured by Goldmann applanation tonometry. The registry identifies the measure as continuous and reports that the summary parameter is a mean with standard deviation. The posted record does not include the mean change or standard deviation for either treatment-use group, nor does it report an overall endpoint result.

Because the study was not randomized and has no control group, the treatment-use groups cannot be interpreted as randomized arms. Differences between them may reflect who received each treatment approach as well as any change during follow-up. The registry record does not report details of how treatment choice was made or whether analyses adjusted for baseline differences. The study dates are recorded as 2018-12-27 for start and 2019-07-26 for primary completion, and its status is completed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The enrolled population includes all subjects who signed ICF. One subject enrolled but withdrew consent before study drug dispensed; thus, post-baseline treatment is unavailable. Participant Flow data represents ITT population. Clarification of enrolled (n= 261) vs treated (n=260) subjects is provided in Recruitment \& Pre-assignment sections.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (mITT) population included all subjects who received at least 1 dose of study medication and had at least 1 follow-up visit with a completed IOP measurement.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Modified intent to treat (mITT) population included all subjects who received at least 1 dose of study medication and had at least 1 follow-up visit with a completed IOP measurement.

6. Primary Endpoint

The registry lists the primary outcome as Intraocular Pressure (IOP), measured over 12 weeks.

The primary endpoint was percent change from baseline IOP at Week 12. IOP is the pressure inside the eye, and Goldmann applanation tonometry is the measurement method identified in the registry. Reporting change relative to baseline expresses the follow-up measurement in relation to each participant’s starting measurement, rather than describing only the pressure observed at follow-up. The registry specifies that the endpoint was summarized as a mean with standard deviation.

In general, a continuous endpoint can retain information about the range of measured values rather than reducing results to a yes-or-no event. A mean describes the central value of the observations, while a standard deviation describes their spread around that mean. The measure may be useful for describing the direction and size of change in IOP over the treatment period. It does not, by itself, establish that any observed change was caused by the study treatment, particularly in an open-label study without a randomized control group.

The registry identifies the primary analysis population as mITT participants who received at least 1 dose and had at least 1 follow-up visit with a completed IOP measurement. The number analyzed and the endpoint estimate are not reported in the registry record. As a result, the posted information does not allow readers to assess the observed mean change, its variability, or how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s main endpoint is continuous: percent change from baseline IOP at Week 12. For a continuous measure, a mean provides a summary of the central tendency of the analyzed observations. The standard deviation describes how dispersed individual observations are around that mean. The registry identifies both the mean and standard deviation as the intended summary, but does not report their values. Consequently, readers cannot reconstruct the observed endpoint distribution or quantify its variability.

In general, an estimate should be read together with a measure of uncertainty. A confidence interval communicates the range of effect values reasonably compatible with the data and the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the model and study design. The registry record does not report a confidence interval for the primary endpoint. It also does not report a p-value or a test of a specified null hypothesis. No statistical significance conclusion about the primary endpoint can therefore be drawn from the posted record.

The mITT population is defined by two conditions: participants had to receive at least 1 dose and have at least 1 follow-up visit with a completed IOP measurement. Such a definition makes the analysis dependent on participants having usable follow-up data. It differs from simply counting everyone enrolled. The number meeting the mITT definition is not reported in the registry record, nor is the number with missing or incomplete Week 12 measurements. That prevents assessment of how much endpoint information was available and whether follow-up availability might have affected the result.

The study was open-label and had no masking. In general, lack of masking can affect behavior, reporting, care decisions, or outcome assessment, depending on the endpoint and setting. IOP was measured with an identified instrument, but the registry does not report procedures for standardizing measurement, masking assessors, or handling repeated measurements. The record also does not describe the statistical model used for the primary analysis, any covariate adjustment, or assumptions about the distribution of the outcome.

The design is listed as single-group with allocation recorded as NA. The two safety groups are described by use of monotherapy or concomitant therapy, but they are not randomized comparison groups. In general, comparisons between nonrandomized groups can be confounded: group membership may be associated with participant characteristics that also relate to the outcome. The registry does not report a method for controlling such differences. A simple difference between group summaries, if one were available, would not on its own isolate a treatment effect.

Over-dispersion is a general concern for count outcomes when observed variation exceeds what a simple count model assumes. It is less central to a continuous mean endpoint such as the primary IOP measure, although the distribution and variability of continuous observations still matter for the model and its uncertainty estimates. The registry does not report a distributional assessment or a method used to address departures from model assumptions.

The record contains sample-size planning assumptions for an illustration based on the observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. These assumptions are not a reported protocol justification for the trial’s enrollment, and the registry does not report the trial’s own sample-size justification. The illustration is a planning exercise, not observed power and not evidence that a particular effect was detected. No calculated illustration values are stated in the registry entries summarized in the record.

In general, a planning calculation asks what sample size might be needed under specified assumptions; it does not reveal the probability that a completed study has found a true effect. Observed power is not a substitute for an effect estimate and confidence interval. For this study, the reported planning assumptions cannot fill the gap left by the absent primary endpoint result.

The registry indicates one outcome measure and one analysis, but does not report whether there were interim analyses, how multiplicity was handled, or a detailed statistical analysis plan. Those details are not reported in the registry record. Without the analysis method, estimate, and uncertainty measure, the primary result cannot be independently interpreted or compared quantitatively with another study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Netarsudil Ophth Sol 0.02% Monotherapy - Tx Naïve ", "Netarsudil Ophth Sol 0.02% Monotherapy - Replaced ", "Netarsudil Ophth Sol 0.02% Monotherapy - Replaced ", "Netarsudil Ophth Sol 0.02% Concomitant Therapy")
n   <- c(24, 61, 6, 151)
m   <- c(-16.9, -2.3, 0.2, -17)
sp  <- c(16.35, 16.23, 8.81, 16.81)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Netarsudil Ophth Sol 0.02% Monotherapy - Tx Naïve   24  -16.900  16.350  -23.804  -9.996
CARM  Netarsudil Ophth Sol 0.02% Monotherapy - Replaced   61  -2.300  16.230  -6.457  1.857
CARM  Netarsudil Ophth Sol 0.02% Monotherapy - Replaced   6  0.200  8.810  -9.046  9.446
CARM  Netarsudil Ophth Sol 0.02% Concomitant Therapy  151  -17.000  16.810  -19.703  -14.297

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study tests multiple outcomes, time points, subgroups, or comparisons, increasing the chance of a false-positive finding if each test is interpreted separately. The registry lists one outcome measure and one analysis, and identifies the primary endpoint as mean percent change from baseline IOP at Week 12. It does not describe a multiplicity adjustment, a hierarchy of outcomes, or whether other analyses were prespecified. Such details are not reported in the registry record, so the approach to multiplicity cannot be assessed.

The record defines the mITT population as participants who received at least 1 dose and had at least 1 follow-up visit with a completed IOP measurement. The number meeting that definition is not reported in the registry record. Nor does the record state how missing Week 12 measurements were handled, whether any values were imputed, or whether sensitivity analyses assessed the effect of missing data. In general, missingness can matter if participants without endpoint measurements differ systematically from those with observed measurements. The available record does not show whether that concern arose or how it was addressed.

Enrollment was 261, but this number should not be assumed to equal the primary analysis population. The registry reports safety counts by treatment-use group, but those do not identify how many participants contributed to the primary endpoint analysis. The analysis population counts and the disposition of participants after enrollment are not reported in the registry record.

The registry record also does not report interim analyses or a detailed statistical analysis plan. It is therefore not possible to determine from the record whether analysis choices were prespecified or how deviations, if any, were treated.

12. 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: malignant melanoma of eyelid (1.0%), pneumonia (1.0%), cellulitis lower left extremity (0.6%).

The registry reports serious adverse event counts separately for netarsudil 0.02% monotherapy and concomitant therapy. In the monotherapy group, 2 of 99 participants were listed as affected by a serious adverse event; in the concomitant-therapy group, 1 of 161 was listed as affected. The record reports 0 deaths in each group. These counts describe what was recorded during the study and should not be treated as a randomized comparison, because the groups were not randomized control arms.

The registry also lists other adverse events for each group: 43 of 99 participants in the monotherapy group and 58 of 161 in the concomitant-therapy group. The record does not provide enough context in these counts alone to determine event severity, duration, relationship to treatment, or whether participants experienced more than one event. Serious-event terms listed include Malignant Melanoma of Eyelid at 1.0%, Pneumonia at 1.0%, and Cellulitis Lower Left Extremity at 0.6%. These entries are descriptive and do not establish causation.

In general, safety counts depend on how adverse events were defined, collected, and attributed. The registry record does not report additional detail on those procedures. Group sizes and treatment circumstances differ, and there is no randomized comparison; therefore, raw counts should not be read as evidence that one treatment approach has a higher or lower risk than another.

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

The registry establishes that a completed, multicenter, open-label Phase 4 study evaluated netarsudil ophthalmic solution 0.02% for elevated IOP in people with open-angle glaucoma or ocular hypertension. It describes treatment for 12 weeks, either as monotherapy or with other IOP-lowering agents, and identifies a primary outcome based on percent change from baseline IOP at Week 12. It also gives the definition of the mITT population and reports adverse-event counts.

What the record does not establish is the magnitude or direction of the primary endpoint result. The numerical endpoint estimate, its standard deviation, and a measure of uncertainty are not reported in the registry record. It is therefore not possible to state how much IOP changed on average, how variable the change was, or how precisely it was estimated. The information also does not support a statistical significance conclusion for the primary endpoint.

The nonrandomized, single-group design is important to interpretation. An observed change from baseline, if reported, would describe change during the study period, but without a randomized control group it would not by itself distinguish treatment-related change from other influences. The monotherapy and concomitant-therapy groups are not like-for-like randomized controls, and any contrast between them could reflect differences in the participants or treatment context.

The record’s safety counts are descriptive. They identify affected participants and listed serious-event terms, but do not establish that an event was caused by treatment or permit a controlled comparison between approaches. The results should therefore be read as a limited registry account of study design and safety reporting, not as a definitive estimate of treatment effect or comparative safety.

In general, a clinical result is most informative when the effect estimate is presented with its uncertainty, analysis population, missing-data handling, and relevant comparison. Several of these details are not reported in the registry record. The available information supports understanding what the study set out to measure, but not a conclusion about the size, precision, or causal interpretation of the primary outcome.

14. Why This Trial Matters Statistically

This study illustrates why a clearly named endpoint is not the same as a fully interpretable result. The registry specifies mean percent change from baseline IOP at Week 12, identifies the measurement method, and defines the mITT population. Those details help clarify what outcome was intended and whose observations were eligible for the primary analysis. But the endpoint estimate and its variability are not reported, so the central statistical result cannot be evaluated from the record.

Its design also makes comparison and causal interpretation important statistical issues. The study was open-label, with no allocation and a single-group model. Although the registry distinguishes monotherapy from concomitant therapy, those groups are not randomized controls. This makes it important not to interpret a difference between them as though treatment assignment had been randomized. General differences in participant characteristics or clinical decisions could contribute to any observed contrast.

The enrollment count and analysis definition also highlight the distinction between recruitment and information in the primary analysis. Enrollment was 261, while the mITT definition required treatment exposure and a follow-up IOP measurement. The number analyzed is not reported in the registry record. Without it, readers cannot tell how much of the enrolled group contributed to the primary result.

Finally, registry reporting is itself part of statistical transparency. The record conveys the research question, endpoint, and some safety counts, while leaving the primary estimate, uncertainty, missing-data handling, and detailed analysis plan unreported. That combination makes this study useful for illustrating how design and reporting determine what conclusions can reasonably be drawn from clinical-trial statistics.

15. 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 central limitation for interpretation is that the primary endpoint result is not reported in the registry record. Although the endpoint, measurement method, time point, and analysis-population definition are given, the mean percent change from baseline, standard deviation, and uncertainty measure are absent. This prevents assessment of the size, direction, and precision of the result.

The study was open-label and had no randomized control group. Monotherapy and concomitant-therapy groups are not like-for-like randomized comparisons, so any between-group contrast could be affected by differences in participants or treatment circumstances. The registry does not report whether treatment choice was adjusted for in an analysis or describe a method for addressing confounding.

The registry reports enrollment of 261 but does not report the number included in the mITT analysis. It also does not describe missing Week 12 measurements, reasons for missing data, or any imputation or sensitivity analyses. Thus, the completeness of primary outcome follow-up and the potential influence of missing observations cannot be evaluated from the record.

Further statistical details are not reported in the registry record, including the primary analysis model, covariate adjustment, handling of multiplicity, interim analyses, and a detailed statistical analysis plan. The registry also does not report measurement-standardization procedures or whether outcome assessors were masked. These omissions limit independent assessment of the analysis assumptions and possible sources of bias.

The safety counts are descriptive and are not a randomized comparison. The registry record does not provide enough detail in the reported counts to determine event-level context or establish causality. These limitations apply to interpretation of the registry information and should not be mistaken for evidence about unreported outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Rhopressa® for the Reduction of Elevated Intraocular Pressure in Patients With Glaucoma or Ocular Hypertension in a Real-world Setting — NCT03808688.
• Registry record last updated 2020-09-29; status last verified 2019-11.
• Results first posted 2020-09-29.
• 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.

19. Record Summary

The registry describes a completed, multicenter, open-label Phase 4 study of netarsudil ophthalmic solution 0.02% in people with open-angle glaucoma or ocular hypertension and elevated IOP. Enrollment was 261. Treatment was given for 12 weeks as monotherapy or concomitantly with other IOP-lowering agents. The design is listed as single-group, with no allocation and no masking.

The primary endpoint was mean percent change from baseline IOP at Week 12, measured by Goldmann applanation tonometry. The mITT population required at least 1 dose and at least 1 follow-up visit with a completed IOP measurement. The primary endpoint estimate and analysis population count are not reported in the registry record.

The record reports serious and other adverse-event counts for the two treatment-use groups and 0 deaths in each. These are descriptive, not randomized comparative results. Details of missing-data handling and the full statistical analysis plan are not reported in the registry record.