Comparing Effectiveness of the Hydrus Microstent (TM) to Two iStents to Lower IOP in Phakic Eyes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Effectiveness of the Hydrus Microstent (TM) to Two iStents to Lower IOP in Phakic Eyes (NCT02023242), a randomized na study. The primary outcome is Unmedicated IOP </= 19 mmHg at 12 Months.

2. Clinical Question

The question combines a pressure threshold with medication status. A participant had to meet the stated pressure criterion while not using ocular hypotensive medication to count as meeting the primary endpoint. It is therefore not simply a comparison of average pressure, nor does it describe everyone who reached the threshold while taking medication.

The randomized comparison estimates the difference between the groups as they were represented in the posted Intent-to-Treat result. It addresses the relative frequency of meeting this specific endpoint at the specified follow-up time. It does not, by itself, describe all aspects of pressure control, medication use, safety, or longer-term outcomes.

3. Trial Design

The registry describes a prospective, multicenter, randomized comparison with a parallel-group model and single masking. Participants were assigned to Hydrus Microstent or iStent Trabecular Micro Bypass. The listed enrollment is 152. The registry records the study as completed, with a start date of 2012-10 and primary completion in 2017-08. The phase is listed as not applicable.

Random allocation is intended to make the groups comparable at the start of a trial, on average, and can support a causal comparison when the study is conducted and analyzed appropriately. A parallel design means participants are assigned to one group rather than crossing between the two device groups. The registry does not report details of the randomization procedure, allocation concealment, or which people were masked.

The primary outcome population is identified as Intent-to-Treat. That label indicates an analysis population based on randomized assignment, but the registry record does not describe how missing outcome measurements or deviations from assigned treatment were handled. The posted primary outcome denominators are 73 for Hydrus Microstent and 75 for iStent Trabecular Micro Bypass; these are the denominators reported for that outcome, not a statement about the handling of every randomized participant.

The sponsor is Ivantis, Inc. The brief description states that the study compared two implantable devices intended to lower pressure inside the eye in people with glaucoma. Additional protocol details, including eligibility criteria beyond the conditions listed, are not reported in the registry record.

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: 152 patients were randomized

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT)

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: Intent-to-Treat (ITT) - All participants randomized and grouped according to their randomization assignment

6. Primary Endpoint

The registry lists the primary outcome as Unmedicated IOP </= 19 mmHg at 12 Months, measured over 12 months.

The primary endpoint is the percentage of participants with intraocular pressure at or below 19 mmHg at 12 months who were not using ocular hypotensive medication. The registry specifies the Intent-to-Treat population. The posted percentages are 34.2% for Hydrus Microstent and 13.3% for iStent Trabecular Micro Bypass.

This is a binary endpoint: each participant either meets the combined pressure-and-medication criterion or does not. A threshold endpoint can make a clinically defined state easier to compare between groups, but it compresses information. It does not show the distribution of individual pressure values, how far measurements were from the threshold, or how pressure changed over time. Nor does the endpoint alone show medication use among participants who did not meet the pressure criterion.

The endpoint is used to summarize the proportion reaching a defined pressure level without medication at a particular follow-up time. Its interpretation depends on both parts of its definition: the pressure threshold and the requirement not to be using ocular hypotensive medication. It should not be read as an average pressure result or as a measure of every possible treatment outcome.

7. Results Posted in the Registry

• iStent Trabecular Micro Bypass: 13.3% (10/75) versus 34.2% (25/73) on control; risk difference -20.9 percentage points (95% CI -34.2 to -7.6), risk ratio 0.39 (0.20–0.75); unadjusted two-proportion z-test p = 0.003.

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.

Unmedicated IOP </= 19 mmHg at 24 Months

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • iStent Trabecular Micro Bypass: 13.3% (10/75) versus 23.9% (17/71) on control; risk difference -10.6 percentage points (95% CI -23.2 to 1.9), risk ratio 0.56 (0.27–1.13); unadjusted two-proportion z-test p = 0.099.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between iStent Trabecular Micro Bypass and the control. The interval gives the range of effects that remain compatible with the data.

Unmedicated IOP </= 18 mmHg at 12 Months

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • iStent Trabecular Micro Bypass: 9.3% (7/75) versus 30.1% (22/73) on control; risk difference -20.8 percentage points (95% CI -33.2 to -8.4), risk ratio 0.31 (0.14–0.68); unadjusted two-proportion z-test p = 0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for iStent Trabecular Micro Bypass than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The listed secondary outcomes extend the primary question to other follow-up times and pressure thresholds, and include medication use. Overall, the posted pattern is directionally consistent with a higher proportion meeting the pressure-without-medication criterion in the Hydrus group for the listed secondary pressure endpoints. The degree of statistical support varies across those comparisons.

These outcomes provide related but not interchangeable information. Changing the follow-up time or pressure threshold changes the question being answered, while medication-use outcomes address a different aspect of the comparison. A consistent direction across related endpoints can add context, but it does not turn each outcome into an independent confirmation of the primary result.

The registry lists four secondary outcomes, but reports no secondary analyses in the analysis records. The posted summaries include unadjusted comparisons. If multiple outcomes are examined, the chance of obtaining at least one apparently strong result can increase; methods for accounting for that issue depend on a prespecified analysis plan. No multiplicity adjustment or hierarchy of confirmatory and exploratory outcomes is reported in the registry record.

For these reasons, secondary findings generally carry less confirmatory weight than a prespecified primary result, especially when the analysis plan and multiplicity handling are unavailable. They can help describe whether the primary pattern is echoed across related measures, but should be interpreted as supportive or exploratory rather than as separate definitive tests.

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

• The Percentage of Subjects Who Are Not Using Ocular Hypotensive Medications at 12 and 24 Months
• Mean Medication Use at 12 and 24 Months
• Unmedicated IOP </= 19 mmHg at 24 Months
• Unmedicated IOP </= 18 mmHg at 12 Months

9. Statistical Interpretation

10. Statistical Methods Explained

What does the risk difference compare?

The reported comparison is a risk difference, which subtracts the outcome proportion in one group from the outcome proportion in the other. The comparison is stated as iStent Trabecular Micro Bypass relative to Hydrus Microstent. Its estimate is -0.209. The negative sign indicates that the observed percentage meeting the endpoint was lower in the iStent group. The two group percentages are 13.3% and 34.2%, respectively.

In general, a risk difference expresses an absolute contrast on the proportion scale. It is distinct from a relative measure, such as a risk ratio or odds ratio, which compares the groups using division or odds. Absolute and relative measures answer different questions, so the risk difference is the most direct measure for describing the absolute separation in endpoint proportions. The registry also posts relative measures, but the main interpretation follows the stated risk difference.

What does the unadjusted p-value mean?

The unadjusted p-value is 0.003. In general, a p-value describes how unusual data at least as different as those observed would be under a specified null model, assuming that model and the analysis assumptions are appropriate. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result occurred by chance in an everyday sense.

“Unadjusted” means the posted value is not reported as corrected for the number of outcomes or comparisons examined. Whether such a correction is needed depends on the prespecified analysis plan and the role of each endpoint. That plan is not reported in the registry record, so the p-value should not be interpreted as if a multiplicity strategy were known.

How should the confidence interval be read?

The reported interval for the primary risk difference extends from -0.342 to -0.076. In general, a confidence interval gives a range of estimates compatible with the observed data under the method’s assumptions. It reflects sampling uncertainty and should be read alongside the point estimate. The interval does not include zero, the value corresponding to no difference on the risk-difference scale.

An interval does not capture every source of uncertainty. It does not account automatically for bias, unreported analysis choices, measurement problems, or differences between the trial population and other populations. The confidence level and method used to construct the posted interval are not reported in the registry record.

Why use a binary endpoint?

In general, a binary endpoint records whether a participant meets a specified condition. Here the condition requires both a pressure at or below 19 mmHg and no use of ocular hypotensive medication at 12 months. This makes the endpoint interpretable as a proportion meeting a defined target, but it discards detail about the exact pressure values and changes over time. Participants just on either side of the threshold count differently, even if their measurements are close.

The endpoint also combines pressure status and medication status. A difference in the proportion meeting it could reflect differences in pressure, medication use, or both. The registry does not provide enough detail in the primary endpoint result to separate those contributions.

What does randomization contribute?

In general, randomization helps balance known and unknown baseline characteristics between assigned groups in expectation. That supports a fair comparison of outcomes by assigned group. It does not guarantee identical groups, eliminate missing data, or prevent bias arising after allocation. The registry identifies the study as randomized but does not report the sequence-generation or concealment procedures.

The primary population is listed as Intent-to-Treat, a designation generally intended to preserve the comparison by randomized assignment. The record does not explain how the population was implemented or how missing endpoint data were treated. Those details matter when assessing whether the analysis retains the protections of randomization.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.209, with an interval from -0.342 to -0.076. The interval is entirely below zero, so the posted range of estimates indicates a lower observed endpoint proportion for iStent relative to Hydrus under the comparison’s stated direction. The interval is not especially narrow: it spans a range of possible group contrasts, which signals uncertainty about the precise size of the difference.

The group percentages, 34.2% and 13.3%, are point estimates from the posted outcome denominators of 73 and 75. The registry does not post confidence intervals for these individual percentages in the primary outcome record. The comparison interval is therefore the available interval estimate for the primary group contrast.

In general, confidence intervals describe sampling precision under the statistical method and its assumptions. They do not account automatically for potential bias, multiplicity, or incomplete outcome data. The registry record does not state the confidence level or the interval-construction method, so those technical details cannot be assessed from the posted record alone.

Precision is different from statistical significance. A result can have an interval that excludes zero while still leaving meaningful uncertainty about the magnitude of the difference. The interval should be considered together with the observed percentages, the endpoint definition, and the limitations of the reported analysis.

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 planning figures are participants per arm, not total participants and not total events. They are illustrations based on the observed effect, rather than the original trial’s design assumptions; those original assumptions are not reported in the registry record. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario targets the stated fraction of the observed effect.

For the primary endpoint, planning for 100% of the observed effect gives 64 participants per arm for 80% power and 86 participants per arm for 90% power. Planning for 75% of the observed effect gives 123 participants per arm for 80% power and 164 participants per arm for 90% power. Planning for 50% of the observed effect gives 295 participants per arm for 80% power and 394 participants per arm for 90% power.

In general, power is the chance that a study would detect an effect of the specified size under the planning assumptions if that effect were present. The 80% and 90% columns represent different target chances of detecting the assumed effect. A higher target power generally requires a larger planned sample. The figures also illustrate that smaller effects need more participants to detect than larger effects under the same assumptions.

These values are prospective planning illustrations calculated from the observed result, not observed power for the completed trial. They do not show the probability that the primary finding is correct or whether the original trial was adequately planned. The original sample-size justification and design assumptions are not reported in the registry record.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.342; treatment proportion p₁ = 0.133; average p̄ = 0.238.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6022 = 1.1802.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5837 = 0.4913.
4. n = (1.1802 + 0.4913)² / (-0.2091)² = 63.9, rounded up to 64 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
p0 <- 0.342465753424658                          # control proportion
p1 <- 0.133333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2023242)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 64 (80% power), 86 (90% power)
 75% of observed effect: n per arm = 123 (80% power), 164 (90% power)
 50% of observed effect: n per arm = 295 (80% power), 394 (90% power)
power.prop.test: 63.9 
Simulated power at n = 64 per arm: 0.809 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and lists four secondary outcomes. It posts unadjusted comparisons for the primary endpoint and secondary outcomes, but the analysis records report no analyses. The statistical analysis plan, including any hierarchy among endpoints or multiplicity procedure, is not reported in the registry record.

Multiplicity arises when several outcomes or comparisons are assessed. In general, conducting more tests can increase the chance that at least one result appears statistically notable even when there is no true effect for any comparison. Whether and how to adjust depends on the planned role of the outcomes, the testing strategy, and the intended interpretation. Without those details, the unadjusted secondary p-values should not be treated as if they controlled an overall error rate.

The primary population is described as Intent-to-Treat. The registry does not report how missing primary endpoint values were handled, whether any imputation was used, or how the analysis addressed participants without a recorded outcome. The posted outcome denominators differ across some endpoints, but the reasons for those denominators are not reported in the registry record.

Other analysis details are also unavailable, including the confidence-interval method, adjustments for baseline factors, and any sensitivity analyses. This absence does not establish that such methods were not used; it means they cannot be evaluated from the registry record. The limitations are particularly relevant when considering whether the primary comparison was the sole planned inferential test and how much weight to place on secondary results.

15. 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: uncontrolled glaucoma (9.1%), cataract (4.0%), wet age related macular degeneration (4.0%), bcva loss >/= 2 lines etdrs >/= 3 months (2.6%), proliferative diabetic retinopathy (1.3%).

The registry reports serious adverse events affecting 7 of 75 at risk in the Hydrus Microstent group and 14 of 77 at risk in the iStent Trabecular Micro Bypass group. Other adverse events affected 24 of 75 and 23 of 77, respectively. The recorded deaths are 0 in the Hydrus group and 1 in the iStent group.

These are descriptive counts with the reported at-risk denominators. They should not be read as a formal statistical comparison: the registry does not post a comparative safety analysis or uncertainty intervals for these figures. The listed serious adverse-event terms include Uncontrolled Glaucoma at 9.1%, Cataract at 4.0%, Wet Age Related Macular Degeneration at 4.0%, BCVA loss of at least 2 lines ETDRS for at least 3 months at 2.6%, Proliferative Diabetic Retinopathy at 1.3%, and IOP Increase at 1.3%. The record does not clearly assign these listed term percentages to a specific group, so they should not be attributed to either device group.

Adverse-event counts describe events recorded in the trial and do not, by themselves, establish whether an event was caused by a device. Further definitions, event timing, and comparative analyses are not reported in the registry record.

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

The posted primary result shows that, at 12 months, a larger observed percentage of participants in the Hydrus Microstent group met the combined criterion of intraocular pressure at or below 19 mmHg without ocular hypotensive medication than in the iStent Trabecular Micro Bypass group. The reported risk difference and interval quantify the group contrast for that endpoint, and the interval does not include zero.

This finding is specific to the enrolled trial population, the two randomized groups, the stated threshold, medication status, and the 12-month assessment. It is not a direct comparison of average pressure or pressure change, and it does not describe every participant’s experience. The binary endpoint does not convey how far pressure values were from the threshold or the contribution of pressure versus medication status to the group difference.

The result does not, on its own, establish the broader effectiveness or safety of either device, settle the relative merits of the devices for every patient, or show what happens beyond the reported follow-up. Nor does a statistically notable result quantify clinical importance. The registry record does not provide the full protocol, detailed analysis plan, or missing-data methods needed to assess all aspects of the result.

In general, a randomized comparison can support interpretation of differences between assigned groups, but its strength depends on conduct, outcome completeness, analysis choices, and applicability to the population of interest. The result is best understood as evidence about one defined endpoint at one stated time point, alongside the uncertainty and reporting limitations.

17. Why This Trial Matters Statistically

This trial illustrates why the definition of an endpoint matters as much as the name of the outcome. “Unmedicated IOP at or below 19 mmHg” combines a pressure threshold with medication status. A comparison of that proportion answers a focused question about reaching a defined state without medication, rather than a general question about average pressure or all aspects of glaucoma care.

It also demonstrates the distinction between an observed group difference and the precision of that estimate. The primary percentages describe the observed outcome in each arm, while the risk difference and its interval express the comparative result and its uncertainty. Reporting the contrast on an absolute scale makes the direction and size of the group separation interpretable without substituting a relative measure.

The secondary outcomes show why a set of related results needs a planned interpretive framework. Outcomes at different thresholds or follow-up times may tell a coherent story, but multiple unadjusted tests do not automatically provide independent confirmation. When the multiplicity strategy and analysis plan are not reported, secondary evidence should be weighed cautiously.

Finally, planning illustrations derived from an observed effect are not the same as the original design justification or an assessment of observed power. Separating those concepts prevents a retrospective calculation from being mistaken for evidence about how the trial was planned or how likely its result was to be detected.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record leaves important design and analysis details unspecified. Although the study is described as randomized, prospective, multicenter, parallel, and single-masked, it does not describe the randomization procedure, allocation concealment, or who was masked. Eligibility details beyond the listed glaucoma conditions and the description of phakic eyes are not reported in the registry record.

The primary outcome is binary and threshold-based. It summarizes whether participants met a combined pressure and medication criterion, but it does not show the distribution of pressure values or separate the pressure and medication components. The registry record does not provide confidence intervals for the group percentages themselves or explain the method used for the interval on the risk difference.

The record identifies the primary analysis population as Intent-to-Treat but does not explain missing-data handling or why outcome denominators vary across measures. It does not report the trial’s original sample-size justification, statistical analysis plan, multiplicity strategy, or sensitivity analyses. The posted secondary comparisons are unadjusted, and no secondary analysis records are listed.

Safety results are reported as counts with at-risk denominators, but no comparative safety analysis is posted. The listed serious adverse-event terms are not clearly allocated by group. The available result therefore does not support detailed attribution or a formal comparison of safety between devices.

These are limitations of what can be evaluated from the registry record; they do not establish that unreported procedures or analyses were not conducted. They do constrain how fully the posted results can be appraised.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparing Effectiveness of the Hydrus Microstent (TM) to Two iStents to Lower IOP in Phakic Eyes — NCT02023242.
• Registry record last updated 2019-12-10; status last verified 2019-11.
• Results first posted 2019-12-10.
• 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.

22. Record Summary

NCT02023242 is a completed, prospective, multicenter, randomized, parallel-group comparison of Hydrus Microstent and iStent Trabecular Micro Bypass in glaucoma. The registry lists enrollment of 152, single masking, and a phase of not applicable. The recorded study start is 2012-10, and primary completion is 2017-08. Ivantis, Inc. is the sponsor.

The primary endpoint is the percentage of the Intent-to-Treat population with intraocular pressure at or below 19 mmHg without ocular hypotensive medication at 12 months. The posted result is 34.2% for Hydrus Microstent and 13.3% for iStent Trabecular Micro Bypass, with a reported risk difference of -0.209 for iStent relative to Hydrus and an unadjusted p-value of 0.003.

The record also lists secondary outcomes involving medication use and pressure thresholds at 12 and 24 months. Key details of the statistical plan, missing-data methods, and multiplicity handling are not reported in the registry record.