Trusopt and Cosopt; Ocular Perfusion Pressure and Blood Flow: New Long-term Prospective Data: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trusopt and Cosopt; Ocular Perfusion Pressure and Blood Flow: New Long-term Prospective Data (NCT01145898), a registered phase not stated study. The primary outcome is 6-month Change in Ophthalmic Artery (OA) Peak Systolic Velocity (PSV).

2. Clinical Question

The study concerns ocular blood flow in patients with glaucoma. Its stated primary endpoint is change in ophthalmic artery peak systolic velocity (PSV) from baseline to the 6 month visit. The broader study summary describes an interest in ocular perfusion pressure, comprehensive ocular blood flow, visual field progression, and optic nerve structural changes. It does not provide results for those outcomes in the record.

3. Trial Design

The registry lists this as a completed study sponsored by Indiana University. Its start is recorded as 2010-06 and its primary completion as 2012-01. The condition is glaucoma, and the enrollment field reports 56. The brief summary, however, describes an ongoing 3 year prospective study involving 120 patients with open angle glaucoma. The record does not explain how that description relates to the enrollment figure, or whether it refers to a broader study cohort or a different scope.

The study is described as prospective, but the registry does not state an allocation method. In particular, it does not establish random assignment. The arm description names “Glaucoma patients,” described as patients with glaucoma. The record also flags that the arms are not a like-for-like control comparison. A controlled treatment effect therefore cannot be interpreted from the design information alone.

The intervention entry names “(Cosopt®, prostaglandin)” and is classified as a drug. The study title names Trusopt and Cosopt, while the brief summary focuses on analyzing Cosopt. Details about the treatment schedule, use of the named medications, eligibility criteria, and follow-up beyond the primary endpoint timeframe are not reported in the registry record.

The primary endpoint is a continuous measure: 6-month change in ophthalmic artery PSV, with baseline and 6 month visits specified. The record lists 14 outcome measures and 14 analyses, but does not provide their complete results in the information. The statistical plan, sample-size justification for the trial, and any interim analyses are not reported in the registry record. Planning illustrations based on an observed effect are not evidence about how the original study was designed.

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: observational study, patients were treated by their physician not by study personel, treatments/interventions were self-reported by the patients, treatment was not necessarily started at glaucoma diagnosis

6-month Treatment

3-year Treatment

Reasons for not completing this period:

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: glaucoma patients:There will be (as shown) differences in the number of subjects based upon the time of analysis due to patient loss, data of insufficient quality at visit, or change in the drug use during period of study (patient switched off treatment by their doctor) so the number of data points varies throughout the analysis by availability.

6. Primary Endpoint

The registry lists the primary outcome as 6-month Change in Ophthalmic Artery (OA) Peak Systolic Velocity (PSV), measured over Baseline and 6 month visits.

The primary endpoint is 6-month change in ophthalmic artery (OA) peak systolic velocity (PSV), measured in cm/sec. The stated timeframe is baseline and 6 month visits. PSV is a measure of blood flow velocity in the ophthalmic artery, so a change in this measure is used to describe how the recorded velocity differs between those visits. The registry describes the measurement as an assessment of change in ocular blood flow.

The endpoint is classified as continuous, and the parameter is the mean. For a continuous measure, a mean describes the central value across participants; the registry identifies standard error as the dispersion statistic. Standard error characterizes the precision of an estimated mean, rather than the spread of individual participants’ measurements. General statistical interpretation depends on having the actual estimate and its uncertainty, neither of which is reported for this endpoint in the registry record.

The registry’s broader study description also mentions ocular perfusion pressure, comprehensive ocular blood flow, visual field progression, and optic nerve structural changes. Those aims provide context, but they do not replace the stated primary endpoint. A recorded change in PSV alone would not establish a change in every other aspect of ocular blood flow or in visual function or optic nerve structure. The registry record does not report the observed PSV change, so its direction, magnitude, and precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measurement, and the registry identifies the mean as the analysis parameter. General statistical explanation: a mean summarizes the average value across observations. In a change analysis, the quantity of interest is the difference between measurements at the specified visits for the participants included in the analysis. The record names baseline and 6 month visits, but does not report the observed mean change or how participant-level changes were calculated.

The registry lists standard error as the dispersion statistic. General statistical explanation: standard error describes the uncertainty in an estimated mean due to sampling variability. It is not the same as the standard deviation, which describes variation among individual measurements. A smaller standard error generally corresponds to a more precise estimate, but the actual standard error is not reported for the primary endpoint. A confidence interval would combine an estimate and its uncertainty to show a range of values compatible with the data under the method used. No confidence interval is reported in the registry record.

A p-value, if reported, would address how compatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It would not measure the size or importance of a change. No p-value or test for the primary endpoint is reported. Because the endpoint estimate itself is absent, neither statistical evidence against a null hypothesis nor the precision of the estimate can be assessed.

What would a within-person change describe?

General explanation: comparing the same participants at baseline and follow-up can describe within-person change over time. Such a comparison does not by itself separate treatment-related change from other explanations, including natural change over time, measurement variation, or differences in who has follow-up data. A comparison with a suitable control group can help address some of these issues, but the registry cautions that the arms are not a like-for-like control comparison and does not state allocation. The record does not specify whether the primary analysis used paired measurements or another method.

How should group comparisons be interpreted?

General explanation: a between-group contrast is most interpretable when groups are comparable and the allocation process is clear. If groups differ at baseline or are formed through non-random processes, observed differences may reflect those characteristics as well as the intervention. Here, allocation is not stated and a like-for-like control comparison is not established. The comparator and detailed treatment assignment are not reported in the registry record, so a causal treatment contrast cannot be reconstructed from the design description.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, not the original trial design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. The record does not provide the numerical planning outputs in the information. These assumptions therefore should not be treated as the study’s protocol, evidence of its original design, or observed power. Planning illustrations describe hypothetical sample sizes under stated assumptions; they do not change what was actually observed.

General explanation: a normal approximation uses a mathematical distribution to approximate the sampling behavior of a statistic. Its suitability depends on the data and analysis. The registry does not report diagnostic checks or details that would show how the approximation applies to this endpoint. Over-dispersion is a concern mainly for count outcomes when variability exceeds the model’s assumptions; it is not a substitute for examining the distribution and variability of a continuous endpoint such as PSV.

What remains unknown about the analysis?

The registry lists 14 outcome measures and 14 analyses, but does not give the full analysis plan, endpoint hierarchy, covariate adjustments, or the methods used for missing observations. It is also not reported how many participants contributed measurements at each visit or which analysis population was used. These omissions limit assessment of assumptions, precision, and the possibility that analysis choices affected the reported results. Since the primary estimate and its uncertainty are not reported, recalculation from posted summary statistics is not possible from this record.

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("Trusopt", "Prostaglandin Alone")
n   <- c(12, 44)
m   <- c(2.32, -0.3)
sp  <- c(1.2, 1.17)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Trusopt  12  2.320  4.157  -0.321  4.961
CARM  Prostaglandin Alone  44  -0.300  7.761  -2.660  2.060

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and 14 analyses. With multiple outcomes or analyses, general statistical practice distinguishes a prespecified primary question from additional questions and considers how repeated testing may affect the interpretation of statistical evidence. The primary endpoint is identified as 6-month change in ophthalmic artery PSV, but a full hierarchy for the other measures is not reported in the registry record. Any multiplicity adjustment, or a rationale for not adjusting, is not reported.

Missing-data methods are not reported in the registry record. The record does not state how missing baseline or follow-up measurements were handled, whether participants with incomplete measurements were excluded, or whether any imputation method was used. The number of participants contributing to the primary analysis is also not reported. Enrollment of 56 does not by itself establish how many had measurements at both visits.

The analysis populations and rules for inclusion are not reported. It is therefore unknown whether the primary analysis included all enrolled participants, a subset with available measurements, or a population defined by another rule. The registry also does not report interim analyses or stopping rules. Without the analysis plan, completeness information, and endpoint estimates, the impact of missing data or multiple analyses on interpretation cannot be evaluated.

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

The registry record describes a prospective study in glaucoma focused on ocular perfusion pressure and blood flow. It identifies a primary endpoint—6-month change in ophthalmic artery PSV—and specifies that the measure is continuous, analyzed as a mean, with standard error as the dispersion statistic. These details explain the intended measurement and the type of summary statistic, but they do not provide the result.

The observed change, standard error, confidence interval, and p-value are not reported in the registry record. Accordingly, the posted information does not establish the direction or size of the endpoint change, or how precisely it was estimated. The study’s stated interest in visual field progression and optic nerve structural changes likewise does not establish findings for those outcomes, which are not reported.

The design information also does not support a clear treatment-effect interpretation. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. The comparator and detailed treatment regimen are not reported. An outcome measured over time can describe change, but without suitable design and analysis details that change cannot be attributed to a particular treatment based on this record.

The enrollment figure and the brief-summary description differ: the registry lists 56, while the summary describes a 3 year prospective study involving 120 patients with open angle glaucoma. The record does not explain the relationship between these figures. They should not be treated as interchangeable counts of participants in the primary analysis. The record therefore supports a description of the research question and endpoint, not a conclusion about the result or its clinical implications.

13. Why This Trial Matters Statistically

This record illustrates why an endpoint definition and an outcome result must be read separately. A precise label—6-month change in ophthalmic artery PSV—identifies what was measured and when. But without the observed mean change and its uncertainty, readers cannot assess the estimated magnitude or its precision. Statistical interpretation requires the estimate and an account of its variability, not just the name of the outcome.

The study also highlights the importance of understanding comparison structure. The title names Trusopt and Cosopt, while the intervention entry names “(Cosopt®, prostaglandin).” Allocation is not stated, the comparator is not identified, and the registry warns that the arms are not a like-for-like control comparison. Those design details matter because a change over time and a difference between groups answer different questions, and neither alone guarantees a causal interpretation.

Finally, the registry contains information that is difficult to reconcile without further detail: enrollment is listed as 56, whereas the brief summary describes a 3 year prospective study involving 120 patients with open angle glaucoma. It also lists 14 outcome measures and 14 analyses without reporting the full statistical plan. These features make clear why analysis populations, missing-data methods, outcome hierarchy, and complete estimates are important to transparent interpretation. In their absence, the research question can be described, but the findings cannot be appraised quantitatively from the registry record.

14. 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 principal limitation for interpreting this study is that the registry record does not report the primary endpoint estimate or its uncertainty. The mean change in PSV, standard error, confidence interval, and p-value are absent. The record therefore does not allow assessment of the size, direction, or precision of the primary result.

The comparison structure is also unclear. Allocation is not stated, the comparator is not specified, and the registry explicitly says the arms are not a like-for-like control comparison. The intervention entry names “(Cosopt®, prostaglandin),” while the title names Trusopt and Cosopt; the treatment regimen and assignment details are not reported. This limits interpretation of any apparent group or time differences as treatment effects.

The population counts are not reconciled: enrollment is 56, whereas the brief summary refers to a 3 year prospective study involving 120 patients with open angle glaucoma. The number included in the primary analysis and the number with measurements at both visits are not reported. Eligibility criteria and details of the study cohort are also not reported in the registry record.

Additional limitations include the absence of reported missing-data methods, analysis populations, multiplicity procedures, and a full statistical plan. Although the registry lists 14 outcome measures and 14 analyses, their hierarchy and results are not provided in the information. The adverse-event entry lists zero at risk and zero affected for serious and other events, with deaths recorded as null; the record does not explain those entries or provide further safety-reporting context.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trusopt and Cosopt; Ocular Perfusion Pressure and Blood Flow: New Long-term Prospective Data — NCT01145898.
• Registry record last updated 2014-01-22; status last verified 2014-01.
• Results first posted 2014-01-22.
• 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.

18. Record Summary

The registry record identifies a completed prospective study sponsored by Indiana University, with glaucoma as the condition. It lists a start of 2010-06, primary completion of 2012-01, and enrollment of 56. The brief summary describes a 3 year prospective study involving 120 patients with open angle glaucoma; the relationship between that description and the enrollment field is not explained.

The study focuses on ocular perfusion pressure and blood flow. Its primary endpoint is 6-month change in ophthalmic artery PSV, measured in cm/sec, with baseline and 6 month visits specified. The outcome is continuous, summarized as a mean with standard error identified as the dispersion statistic. The record lists 14 outcome measures and 14 analyses.

Allocation is not stated, and the registry says the arms are not a like-for-like control comparison. The comparator is not reported. The primary estimate, its uncertainty, missing-data methods, analysis populations, and statistical plan are not reported in the registry record.