This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Sirolimus Versus Anti-Vascular Endothelial Growth Factor (antiVEGF) for Wet AMD (NCT02357342), a randomized phase 2 study. The primary outcome is Change in Edema From Baseline to Month 6 Central Subfield Thickness ) on Heidelberg Optical Coherence Topography.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02357342 |
| Phase | Phase 2 |
| Condition | Age-Related Macular Degeneration |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 40 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Maturi, Raj K., M.D., P.C. |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned subjects with wet age-related macular degeneration and persistent intraretinal or subretinal edema due to neovascular AMD despite previous anti-VEGF treatment. The registry record does not report further eligibility details or a more specific analysis population.
Intervention
The intervention was intravitreal sirolimus. The trial was designed to assess its safety and efficacy in the stated clinical setting, but the registry record does not give additional dosing or treatment-schedule details.
Comparator
The comparator was standard-of-care intravitreal anti-VEGF injections. The registry record identifies this as the control arm but does not report further details about which anti-VEGF agents or treatment schedules were used.
Primary question
The primary outcome asked how central subfield thickness changed from baseline to month 6 in each treatment group, as measured on Heidelberg optical coherence topography. The posted results give a mean change for each group. They do not report a formal between-group analysis for this primary outcome, so the registry record does not establish the size or precision of a comparative treatment effect on that measure.
This question is specific to a randomized, subject-masked Phase 2 study with a posted enrollment of 40. The central statistical distinction is between describing change within each arm and estimating a difference between arms. The former is available for the primary measure; the latter is not reported in the registry record.
3. Trial Design
The registry describes a randomized, single-masked, parallel-group Phase 2 trial at a single site. It lists enrollment of 40 and a completed status. The recorded start is 2015-04 and primary completion is 2017-01. The sponsor is Maturi, Raj K., M.D., P.C.
Participants were assigned to intravitreal sirolimus or standard-of-care intravitreal anti-VEGF injections. The registry describes the study as subject-masked; further information about who was masked, how masking was maintained, or whether masking was assessed is not reported in the registry record. Details of the randomization sequence and allocation concealment are also not reported in the registry record.
The primary outcome was change in central subfield thickness from baseline to 6 months. The posted arm counts for that outcome are 18 for sirolimus and 20 for standard-of-care anti-VEGF. These are the counts attached to the outcome results; the registry record does not explain how they relate to the overall enrollment or report the reasons for any difference.
Best corrected visual acuity is listed as a secondary outcome. The record posts one secondary outcome and three outcome measures, but no reported analyses are listed. It does not report a detailed analysis plan, the planned sample-size justification, interim analyses, or a description of the analysis population. The posted results therefore support a limited account of study structure and outcome summaries, not a reconstruction of the full protocol or statistical plan.
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.
First 6 Months
| Stage | Sirolimus | Standard of Care Intravitreal Anti-VEGF |
|---|---|---|
| STARTED | 20 | 20 |
| COMPLETED | 18 | 20 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | Sirolimus | Standard of Care Intravitreal Anti-VEGF |
|---|---|---|
| Death | 2 | 0 |
Extension Study
| Stage | Sirolimus | Standard of Care Intravitreal Anti-VEGF |
|---|---|---|
| STARTED | 4 | 9 |
| COMPLETED | 4 | 9 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Sirolimus | Standard of Care Intravitreal antiVEGF | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 20 | 40 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 2 | 2 |
| Age, Categorical: >=65 years | Participants | 20 | 18 | 38 |
| Sex: Female, Male: Female | Participants | 12 | 16 | 28 |
| Sex: Female, Male: Male | Participants | 8 | 4 | 12 |
| Region of Enrollment: United States | participants | 20 | 20 | 40 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Edema From Baseline to Month 6 Central Subfield Thickness ) on Heidelberg Optical Coherence Topography, measured over Baseline to 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | microns |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the change in edema from baseline to month 6, represented by the mean difference in central subfield thickness, measured in microns on Heidelberg optical coherence topography. Central subfield thickness is an imaging measure used to quantify retinal structure. In general, measuring change from a baseline value can describe how that measurement differs at follow-up, while using the same stated measure across treatment groups permits a potential comparison of their changes.
A negative change means the recorded thickness at follow-up is lower than at baseline; a positive change means it is higher. That direction describes the measurement, not by itself a clinical benefit or a causal treatment effect. A between-group estimate would be needed to quantify the contrast in changes, with uncertainty around that contrast to show its precision.
The registry gives group means and full ranges, but it does not report a formal comparative estimate, confidence interval, or p-value for the primary outcome. The reason is recorded as values missing or not estimable for a two-arm comparison. Consequently, the arm-level summaries describe the observed data but do not answer the comparative question with a reported estimate of precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary endpoint, the posted mean change from baseline to month 6 was -30.0 microns in the sirolimus arm, with 18 participants and a full range from -136.0 to 76.0. In the standard-of-care intravitreal anti-VEGF arm, the mean change was 7.5 microns, with 20 participants and a full range from -113.0 to 128.0. These are descriptive summaries of change within each arm.
The ranges show that individual observed changes varied substantially in both groups and extended in both negative and positive directions. A mean is a summary of the group, not a description of every participant. The registry does not post a standard deviation or another dispersion estimate for these primary results; it reports full ranges. Ranges alone do not show how observations are distributed between their endpoints, and they do not provide the standard error needed to assess the precision of a mean.
Most importantly, no between-arm primary comparison is reported. The record explicitly identifies values as missing or not estimable for a two-arm comparison for this outcome. It would therefore be inappropriate to treat the two arm means as a reported treatment contrast, or to claim a formal difference, statistical significance, or a confidence interval for that difference. The posted summaries permit a description of the observed arm-level changes, but the uncertainty around a comparative effect is not available from the registry record.
The secondary visual-acuity outcome has a posted count of 9 in each arm. Its accompanying comparison reports a risk difference of 0.05 and an unadjusted p-value of 0.758. The record also gives risk-ratio and odds-ratio estimates, but it does not describe the underlying binary criterion in enough detail to explain what counted as the event. The secondary result should therefore be read as a registry-posted comparison, not as a complete clinical interpretation of visual acuity. Its unadjusted status and the absence of a reported multiplicity plan further limit the weight that can be placed on it.
These results do not establish that the treatments are equivalent. A non-significant secondary p-value is not evidence that any difference is absent, and the primary outcome has no reported comparative test to interpret. The small posted arm counts, wide observed ranges, and missing primary contrast leave the comparative precision unresolved. No conclusion about benefit or lack of benefit should be drawn from the descriptive primary summaries alone.
9. Statistical Methods Explained
Randomization is intended, in general, to make treatment groups comparable at the point of assignment by distributing measured and unmeasured prognostic factors without systematic selection. That rationale does not guarantee balance in a particular small trial. The registry identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or detailed implementation, so those features cannot be evaluated from the record.
What do the primary arm summaries describe?
The primary outcome is a change score: follow-up central subfield thickness relative to the baseline measurement. The registry reports a mean change for each group. A group mean summarizes the average observed change among the participants counted for that outcome. It does not, on its own, estimate the randomized contrast between groups. A comparison would ordinarily be reported as a difference between group summaries or as an adjusted model estimate, accompanied by an uncertainty measure and a specified analysis method. No such primary comparison is reported in the registry record.
The record gives the full range for each arm rather than a standard deviation or standard error. In general, a range identifies the lowest and highest recorded values but not how densely observations cluster within that interval. It is therefore not a substitute for a standard deviation or a confidence interval. The available range also cannot reveal whether the mean is sensitive to a small number of unusually high or low observations.
How should a confidence interval be understood?
In general, a confidence interval expresses uncertainty in an estimate under a specified statistical procedure. A narrower interval indicates greater precision than a wider interval on the same scale, while an interval that includes a null value is compatible with a range of effects that includes no difference. A confidence interval does not give the probability that the true effect lies within the particular calculated interval. The primary outcome has no reported comparative confidence interval, so its comparative precision cannot be assessed this way.
The secondary outcome includes a risk-difference estimate and an unadjusted p-value. A risk difference compares event proportions between groups, with the direction depending on the stated group ordering. The registry reports an estimate of 0.05 and p = 0.758. In general, a p-value measures how incompatible the observed data are with a specified null model, under its assumptions; it is not the probability that the null hypothesis is true. This p-value is unadjusted, and the registry record does not report a multiplicity procedure. It should not be read as a definitive test of the trial’s broad clinical question.
The registry also reports relative effect measures for that secondary outcome. In general, a risk ratio compares event probabilities and an odds ratio compares event odds. Their interpretation depends on a clearly defined event and group ordering. Although the posted results contain estimates for these measures, the event criterion and a detailed endpoint definition are not reported in the registry record. Those omissions constrain clinical interpretation.
What does the planning illustration mean?
The record includes a sample-size planning illustration based on the observed secondary effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. Its rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For 80% power, the stated participants per arm are 1,565, 2,779, and 6,243, respectively; for 90% power, they are 2,095, 3,720, and 8,357, respectively.
In general, power is the probability that a specified statistical test will reject a null hypothesis under a particular assumed effect and model. A planning calculation asks how many participants would be needed under stated assumptions. It does not measure the power achieved by a completed trial. These figures are explicitly a planning illustration based on the observed effect, not the trial’s own design justification. The planned sample-size rationale is not reported in the registry record. The primary endpoint also lacks a posted two-arm estimate, so the illustration should not be treated as planning evidence for the primary outcome.
Over-dispersion is a general concern when outcomes vary more than a simple statistical model assumes. It can make standard errors too small and intervals too narrow if not accounted for. The registry record does not report a model-based primary analysis or enough dispersion information to assess that issue for the primary endpoint. It is therefore not possible to determine whether a particular model assumption was checked or whether an adjustment was used.
Finally, the record does not state how missing outcome values were handled, whether analyses followed assigned treatment, or whether any adjustment for baseline values or other covariates was made. Those choices can affect estimates and precision. Without a posted analysis plan and comparative primary analysis, the endpoint summaries remain descriptive rather than a complete inferential analysis of the randomized comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity plan. It does not say whether the primary outcome was intended as the sole confirmatory test, whether secondary outcomes were arranged in a hierarchy, or whether any adjustment was planned for multiple testing. The one listed secondary outcome has an unadjusted p-value. In general, when several hypotheses are tested, the probability of at least one chance finding can rise; a prespecified strategy helps clarify which results are confirmatory and how their uncertainty should be interpreted.
Missing-data methods are also not reported. The posted primary counts are 18 for sirolimus and 20 for standard-of-care anti-VEGF, while total enrollment is 40. The registry does not explain the relationship between those figures, identify missing measurements, state reasons for missingness, or describe an imputation or sensitivity-analysis approach. The posted counts alone do not establish why they differ from enrollment or whether missing outcomes affected the results.
The analysis population is not reported in the registry record. It is not stated whether the posted results include all randomized participants, only participants with measured outcomes, or another defined group. The record also does not say whether participants were analyzed according to randomized assignment or whether any exclusions were made after randomization. These details matter because decisions about inclusion can affect the comparability created by randomization.
Interim analyses, stopping rules, and the detailed statistical analysis plan are not reported in the registry record. The record does not give the trial’s sample-size justification either; the posted planning illustration is explicitly based on an observed effect and is not the trial’s design calculation. As a result, readers cannot assess from the registry whether the analysis followed a prespecified plan or how missing observations and multiple outcomes were intended to be handled.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sirolimus | 1 | 20 | 5.0% |
| Standard of Care Intravitreal Anti-VEGF | 1 | 20 | 5.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sirolimus | 2 of 20 |
| Standard of Care Intravitreal Anti-VEGF | 0 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sirolimus | 14 of 20 |
| Standard of Care Intravitreal Anti-VEGF | 15 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Sirolimus | Standard of Care Intravitreal Anti-VEGF |
|---|---|---|---|
| pulmonary embolism | Vascular disorders | 1 of 20 | 1 of 20 |
| myocardial infarction | Cardiac disorders | 1 of 20 | 0 of 20 |
| pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 20 | 0 of 20 |
| subretinal hemorrhage | Eye disorders | 1 of 20 | 0 of 20 |
| central retinal artery occlusion | Eye disorders | 1 of 20 | 0 of 20 |
| anterior chamber inflammation | Eye disorders | 1 of 20 | 0 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sirolimus | Standard of Care Intravitreal Anti-VEGF |
|---|---|---|---|
| decreased visual acuity | Eye disorders | 5 of 20 | 1 of 20 |
| corneal irritation | Eye disorders | 2 of 20 | 2 of 20 |
| increased intraocular pressure | Eye disorders | 2 of 20 | 1 of 20 |
| intraretinal hemorrhage | Eye disorders | 1 of 20 | 1 of 20 |
| Subretinal Hemorrhage | Eye disorders | 1 of 20 | 1 of 20 |
| Sinusitis | Infections and infestations | 1 of 20 | 1 of 20 |
| photopsia | Eye disorders | 0 of 20 | 1 of 20 |
| underactive thyroid | Endocrine disorders | 0 of 20 | 1 of 20 |
| unexplained vision Loss | Eye disorders | 1 of 20 | 0 of 20 |
| hypothyroidism | Endocrine disorders | 1 of 20 | 0 of 20 |
Serious events with the highest arm-level rate: pulmonary embolism (5.0%), myocardial infarction (5.0%), pneumonia (5.0%), subretinal hemorrhage (5.0%), central retinal artery occlusion (5.0%).
The registry posts serious adverse event figures for 20 participants at risk in each arm. It reports one participant affected by a serious adverse event in each arm. The recorded death count is 2 in the sirolimus group and 0 in the standard-of-care intravitreal anti-VEGF group. The record also lists other adverse events in 14 participants in the sirolimus group and 15 in the comparator group.
These counts are descriptive. They do not, by themselves, establish that a treatment caused an event or that the groups differ in safety. In general, safety comparisons require attention to event definitions, duration of observation, exposure, severity, and the number of participants assessed. The registry record does not provide enough information to evaluate those elements or to interpret the deaths’ causes or relationship to treatment.
The listed serious-event terms each carry a posted frequency of 5.0%: pulmonary embolism, myocardial infarction, pneumonia, subretinal hemorrhage, central retinal artery occlusion, and anterior chamber inflammation. The record does not specify the treatment-arm attribution for each listed term in the summary, nor does it give detailed timing or relatedness. These entries should not be treated as a complete account of all event details or as evidence of causality.
12. What the Result Does, and Does Not, Mean
The primary results describe observed mean changes in central subfield thickness within each randomized arm over the stated baseline-to-month-6 interval. The sirolimus arm’s posted mean change was -30.0 microns, and the standard-of-care intravitreal anti-VEGF arm’s was 7.5 microns. The full ranges show that observed participant-level changes varied in both groups. These summaries can orient readers to the direction and spread of the recorded measurements, but they are not a formal estimate of the comparative effect.
The registry record does not report a primary between-arm estimate, confidence interval, or p-value. Without that comparative analysis, the uncertainty around the treatment contrast cannot be quantified from the primary results. It is not justified to infer statistical significance from the separate arm means or to conclude that the treatments are equivalent because a comparison is absent.
The secondary visual-acuity result supplies a separate, unadjusted comparison, but its event definition is not reported in enough detail to give the count a fuller clinical meaning. Its unadjusted p-value is not evidence that there is no difference, and it cannot substitute for the missing primary comparison. The record also does not report the multiplicity strategy, analysis population, or missing-data handling.
In general, statistical results address particular outcomes, populations, time points, and assumptions. A result for central subfield thickness does not automatically describe visual acuity or safety, and a summary at 6 months does not establish longer-term outcomes. The registry record contains a completed Phase 2 study with limited posted results; it does not support a definitive claim about clinical benefit, lack of benefit, equivalence, or comparative safety. Those claims would require more complete outcome definitions, prespecified analyses, and estimates with interpretable uncertainty.
13. Why This Trial Matters Statistically
This trial illustrates a key distinction in clinical statistics: arm-level change summaries are not the same as a randomized between-arm treatment-effect estimate. The registry reports means and ranges for the primary outcome but marks a two-arm comparison as missing or not estimable. A reader can describe the posted measurements, yet cannot use them to quantify the primary comparative effect or its precision from the registry record.
The distinction matters because randomization supports a comparison of assigned groups, while interpretation requires an analysis that actually estimates that comparison. Reporting means separately does not show how uncertain their contrast is. The ranges provide information about observed extremes, but they do not replace a standard error or confidence interval for the treatment contrast.
The record also demonstrates why a posted p-value needs context. The secondary visual-acuity comparison is unadjusted, its binary event definition is not fully reported, and the multiplicity strategy is unknown. Those limitations make it less suitable for strong confirmatory interpretation. The planning illustration is likewise not evidence of achieved power; it is a prospective calculation based on an observed effect under stated assumptions.
For clinical researchers and biostatisticians, the practical lesson is to distinguish what the record directly documents from what would require a fuller statistical report. Clear endpoint definitions, analysis populations, missing-data methods, prespecified comparisons, and uncertainty estimates are essential to interpret a randomized trial. Their absence does not erase the descriptive findings, but it places firm limits on the inferences those findings can support.
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.
Several limitations are specific to the posted record. The primary endpoint has arm-level means and full ranges, but no reported comparative estimate or uncertainty measure. The recorded reason is that values are missing or not estimable for a two-arm comparison. This prevents a direct assessment of the primary randomized contrast.
The posted primary outcome counts are 18 and 20, while enrollment is 40. The registry record does not explain the difference or describe whether participants lacked a month-6 measurement, were excluded, or entered another analysis set. Reasons for missingness and the approach to missing outcomes are not reported. Thus, the completeness and selection of the outcome data cannot be evaluated from the record.
The visual-acuity outcome is described as a number of participants, but the binary definition behind the count is not reported. Although an unadjusted comparison is posted, the registry does not give a multiplicity plan or an analysis hierarchy. This limits the interpretation and confirmatory weight of that secondary result.
Further details about randomization, concealment, masking procedures, treatment schedules, and analysis methods are not reported in the registry record. The record also lacks a reported sample-size justification, interim-analysis details, and a detailed analysis population. These omissions do not prove that such procedures were absent; they mean their conduct cannot be assessed from the registry record.
Finally, safety information is presented as counts and selected serious-event terms without detailed attribution, timing, relatedness, or causes of death. The summaries therefore provide only a limited description of recorded events and do not support a complete comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sirolimus Versus Anti-Vascular Endothelial Growth Factor (antiVEGF) for Wet AMD — NCT02357342.
- Registry record last updated 2017-06-22; status last verified 2017-06.
- Results first posted 2017-06-05.
- 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.
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18. Record Summary
NCT02357342 is a completed, randomized, single-masked, parallel-group Phase 2 study of intravitreal sirolimus versus standard-of-care intravitreal anti-VEGF injections for wet age-related macular degeneration. It was described as a single-site study, with enrollment of 40 and primary completion in 2017-01.
The primary outcome was change in central subfield thickness from baseline to 6 months. Posted results include a mean and full range for each arm, but no two-arm primary analysis. Best corrected visual acuity is listed as a secondary outcome, with an unadjusted comparison posted. The registry record does not report a detailed analysis plan, multiplicity method, missing-data approach, or analysis population, limiting the strength of comparative interpretation.