Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Central Retinal Vein Occlusion (CRVO): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Central Retinal Vein Occlusion (CRVO) (NCT01976312), a randomized phase 3 study. The primary outcome is Average Change in Visual Acuity (Letters) From Baseline to Month 1 Through Month 3.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel-group Phase III study sponsored by Novartis Pharmaceuticals. Its stated purpose was to provide efficacy and safety data on intravitreal ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to CRVO. The study status is completed. The recorded start date is 2013-11-12, and the primary completion date is 2016-03-14. Enrollment is listed as 252.

One group was assigned ranibizumab 0.5 mg, described as PRN intravitreal injection. The other was assigned sham injection; its arm description says ranibizumab 0.5 mg PRN intravitreal injections began as of Month 3. The registry therefore describes a sham comparison with a later treatment component, rather than an unchanged sham condition throughout the period covered by all outcomes. Further details of the transition are not reported in the registry record.

The primary measure was change in best corrected visual acuity (BCVA), expressed in letters, averaged over monthly assessments from Month 1 to Month 3 and compared with baseline. BCVA was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. The registry identifies the Full Analysis Set as patients to whom study treatment had been assigned and says they were analyzed according to their randomized group, following the intent-to-treat principle.

The original design assumptions, including any planned sample-size rationale, are not reported in the registry record. Details of the randomization procedure, masking procedures, and protocol deviations are also not reported in the registry record. The enrollment figure describes the trial record; it should not be treated as a substitute for the group-specific numbers used in individual analyses.

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: This study consisted of the 3 periods (Screening period: Day -14 to Day -1; treatment period: Day 1 to Month 11; post-treatment period: Month 11 to Month 12). At Baseline (Visit 2, Day 1), eligible patients were randomized in a 3:1 ratio to one of the treatment arms

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. (MV-LOCF)=Mean value interpolation and last observation carried forward

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Average Change in Visual Acuity (Letters) From Baseline to Month 1 Through Month 3, measured over Baseline, 3 Months.

The primary endpoint is average change in BCVA, measured in letters, from baseline to Month 1 through Month 3. BCVA is a measure of visual acuity: in this study it was assessed with ETDRS-like testing charts while participants were sitting, beginning at a testing distance of 4 meters. The registry says that monthly assessments from Month 1 to Month 3 were averaged and compared with baseline.

As a general statistical point, a continuous endpoint retains information about the magnitude of change rather than reducing each participant’s result to a category such as improved or not improved. Averaging repeated assessments over a specified period can describe performance across that period rather than at a single visit. It also means the endpoint is a summary across the stated assessment months, not an isolated Month 3 measurement.

The group means describe average change, while the standard deviations describe how much individual observations varied around those averages. The endpoint is a measure of visual acuity, not a direct measure of every aspect of vision, daily functioning, or quality of life. The registry lists patient-reported outcomes and other visual measures among secondary outcomes, but they are separate from this primary endpoint.

7. Results Posted in the Registry

• Ranibizumab 0.5 mg: mean 11.30 versus -2.70 on control; difference 14.00 (95% CI 10.21 to 17.79), standardized effect d = 1.20; z-test p = <0.001.

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.

Average Change of Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 12

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ranibizumab 0.5 mg: mean 12.40 versus 3.20 on control; difference 9.20 (95% CI 5.21 to 13.19), standardized effect d = 0.75; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Ranibizumab 0.5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The numerical secondary BCVA summary has the same direction of group averages as the primary result. Its recalculated group difference is smaller than the primary-period difference. This broad consistency in direction is relevant context, but the later summary measures a different follow-up period and does not constitute a replication of the primary endpoint.

The sham arm description states that ranibizumab PRN injections began as of Month 3. That treatment history matters when interpreting outcomes extending to Month 12: the later contrast is not simply a comparison of continued ranibizumab against sham throughout follow-up. The registry record does not give enough information to separate the effect of the initial assignment from the later treatment course.

The registry lists additional secondary outcomes involving BCVA over time, central-sub-field thickness, letter-improvement and letter-loss categories, and NEI-VFQ-25 patient-reported scores. Numerical results for these listed measures are not reported in the registry record. The overall pattern across them therefore cannot be assessed from the posted numerical summaries.

General statistical explanation: secondary outcomes usually have less evidential weight than a prespecified primary endpoint, especially when many outcomes or time points are examined. Without a reported multiplicity strategy, repeated testing can increase the chance of at least one apparently notable result under a collection of null effects. The registry does not report whether secondary-outcome p-values were adjusted or whether a formal hierarchy was used. Accordingly, unadjusted secondary findings, where available, should be treated as supportive or exploratory rather than as independent confirmation of the primary result.

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

• Average Change of Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 12
• Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time
• Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time
• Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time
• Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time
• The Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 3, 6 and 12 Compared to Baseline

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s BCVA change is measured in letters, and the posted group summaries are means with standard deviations. A mean describes the average value within a group. A standard deviation describes the spread of individual values around that group mean; it is not the standard error of the mean and is not an interval for the group average.

What does the mean difference represent?

The recalculated mean difference compares the posted group means by expressing the ranibizumab group’s mean change relative to the sham group’s mean change. For the primary outcome, the estimate is 14.0 letters. This is a simple unadjusted contrast of the posted summaries. It does not control for baseline variables, account for repeated observations through a fitted longitudinal model, or establish that the estimate is free from bias due to missing data. Whether the sponsor’s analysis used any additional adjustments is not reported in the registry record.

The reported group standard deviations are 10.77 and 13.92. A pooled standard deviation is also listed for the recalculation, along with a standardized effect-size estimate. In general, a pooled standard deviation combines within-group variability to express a difference relative to a common scale of spread. A standardized effect size expresses a mean difference in standard-deviation units. Such standardized quantities can help compare measures on different scales, but they do not replace the original letter scale, which is more directly interpretable for this endpoint.

What does the interval add?

A confidence interval is a range of values compatible with the data and the statistical method, under the method’s assumptions. It conveys uncertainty around an estimated effect and shows which effect sizes remain plausible under that calculation. The primary recalculated interval runs from 10.21 to 17.79. The confidence level and the full calculation details are not reported in the registry record, so the interval should be read as the posted recalculation rather than attributed to an undocumented model.

General statistical interpretation: an interval is not a guarantee that the true effect lies within its endpoints, nor does it show the spread of participant-level outcomes. Its width depends on factors such as variability, sample information, and the method used. A narrow interval can indicate greater precision for the particular estimate, but precision does not resolve concerns about outcome measurement, missing observations, or generalizability.

How should the p-values be read?

The recalculated unadjusted p-value is p < 0.001. The registry-reported analysis also gives p < 0.001 and names the Cochran-Mantel-Haenszel method. In general, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It does not measure the size or importance of an effect. It is also not a probability that a result is due to chance or that a hypothesis is true.

The posted recalculation is based on a difference in continuous group means, while the named registry test is Cochran-Mantel-Haenszel. The registry does not report the test’s detailed implementation, any stratification variables, or an estimate and interval from that test. Consequently, the recalculated mean difference and the registry p-value should not be presented as if they necessarily came from the same statistical model.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model expects. It can make standard errors too small and tests too optimistic if the model does not allow for the extra variation. This primary endpoint is summarized with means and standard deviations; the registry does not report an over-dispersion assessment or a model for this continuous outcome. It is therefore not possible to say that over-dispersion was detected or how it was handled.

The outcome description says monthly assessments were averaged across Month 1 to Month 3. Repeated measurements from the same participant are generally correlated, so an analysis of the individual repeated measurements may need to account for that correlation. The posted endpoint is an average over the period, and the registry does not provide enough detail to determine whether a more detailed longitudinal model was used in the sponsor’s analysis.

The population description identifies the Full Analysis Set and says participants were analyzed according to randomized assignment. It also contains the term MV-LOCF and begins to expand it as mean value interpolation and last observation carried..., but the description is incomplete. The exact rules for missing values, the number of participants with missing endpoint data, and any sensitivity analyses are not reported in the registry record.

11. Confidence Intervals and Precision

The primary unadjusted recalculation estimates a mean difference of 14.0 letters, with an interval from 10.21 to 17.79. The interval’s span represents statistical uncertainty around the estimated difference under the recalculation. The confidence level and the specific interval construction are not reported in the registry record, so no confidence percentage should be attached to these bounds.

The group standard deviations are 10.77 letters for ranibizumab and 13.92 letters for sham. They describe participant-level spread, not uncertainty in the group means. The recalculation lists standard errors of 0.785 for the ranibizumab group and 1.768 for the sham group. A standard error describes the estimated sampling variability of a statistic under a particular method; it is distinct from the standard deviation of individual observations.

As a general statistical point, an interval can be used to judge both the direction and the range of effects compatible with the data. Here, both reported bounds for the recalculated difference are above zero. That does not mean the interval captures every source of uncertainty: the calculation is unadjusted and does not address possible bias from missing data, limitations of the outcome, or differences between the recalculation and the sponsor’s analysis. Nor does the interval establish whether the estimated difference is clinically important.

The registry’s own analysis reports p < 0.001 but gives no estimate or interval for that test. The uncertainty described by the recalculated interval therefore belongs to the unadjusted summary-statistic comparison, not automatically to the Cochran-Mantel-Haenszel analysis. Further model details and the interval confidence level are not reported in the registry record.

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 event counts. The stated illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects equal to the stated fraction of the observed effect. These are planning assumptions for an illustration; the trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column uses a higher target chance of detecting that effect and therefore gives a larger planning figure. These are conditional planning calculations, not guarantees about a future study.

The rows describe planning for 100%, 75%, and 50% of the observed effect. As the effect being planned for becomes smaller, more participants are needed to distinguish it from random variation at the stated significance level and power target. The values use the observed effect as their reference, so they should not be taken as an independent estimate of an effect that a future study will necessarily find.

This is not observed power. The calculation is an illustration of planning requirements under the listed assumptions, not a measure of the probability that the completed trial detected its result. The original design rationale and the assumptions used by the trial team 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 14.000; pooled standard deviation σ = 11.624.
2. n = 2 × (1.96 + 0.842)² × 11.624² / 14.000² = 10.8, rounded up to 11 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 14                      # observed difference in means
sigma <- 11.6242278099416                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1976312)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 11 (80% power), 15 (90% power)
 75% of observed effect: n per arm = 20 (80% power), 26 (90% power)
 50% of observed effect: n per arm = 44 (80% power), 58 (90% power)
power.t.test: 11.9 
Simulated power at n = 11 per arm: 0.767 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry identifies the sponsor’s reported analysis as Cochran-Mantel-Haenszel and reports p < 0.001 for the comparison. It does not provide an effect estimate, interval, or further detail about how that analysis was implemented. The unadjusted recalculation from the posted continuous summaries gives a mean difference of 14.0 letters, with an interval from 10.21 to 17.79 and p < 0.001.

These results point in the same inferential direction, but the methods are not identical descriptions. The recalculation compares group means using posted summary statistics; the registry names a different test for its reported analysis. Because the registry does not report the sponsor analysis estimate or its interval, the two sets of numbers cannot be compared as if they were outputs from the same model. The registry-reported analysis should be distinguished from, rather than replaced by, the unadjusted recalculation. No discrepancy is flagged in the posted results.

Details such as model specifications, adjustment variables, stratification, and handling of missing values for the sponsor’s test are not reported in the registry record. The reported p-value alone cannot supply those missing details or establish the magnitude and precision of the sponsor’s estimated effect.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists several secondary outcomes, but a multiplicity plan is not reported in the registry record. Multiplicity refers to the statistical issue that arises when more than one hypothesis, outcome, time point, or comparison is tested. General statistical explanation: the more tests that are conducted, the greater the chance of at least one small p-value arising even when the corresponding null hypotheses are true. A prespecified adjustment or testing hierarchy can address this concern, but the record does not describe one.

The primary registry-reported test has p < 0.001, and the unadjusted recalculation also has p < 0.001. The posted secondary summary has an unadjusted recalculated p-value of p < 0.001. The registry does not state whether these secondary tests were part of a confirmatory testing sequence, whether their p-values were adjusted, or how the listed but numerically unreported outcomes were analyzed. The results should not be treated as though multiplicity control is established.

The Full Analysis Set is described as all patients to whom study treatment had been assigned, analyzed according to randomized group under the intent-to-treat principle. This identifies the intended analysis population, but it does not report the number of participants contributing data to each endpoint or visit. The group-specific numbers in the outcome summaries may differ from enrollment and from safety denominators; the registry does not explain all such differences.

The population description includes the abbreviation MV-LOCF and an incomplete expansion beginning mean value interpolation and last observation carried.... The detailed imputation rules, the amount and reasons for missing data, and sensitivity analyses for missingness are not reported in the registry record. General statistical explanation: missing-data methods can affect estimates when the probability of an observation being missing is related to its value or to participant characteristics. Without the protocol-level rules and missingness summaries, it is not possible to assess that issue fully.

Interim analyses, stopping rules, and the complete statistical analysis plan are not reported in the registry record. Their absence from the record does not show that such procedures were or were not used.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: macular fibrosis (20.0%), acute myocardial infarction (1.8%), left ventricular dysfunction (1.8%), angle closure glaucoma (1.8%), wrist fracture (1.8%).

The registry gives serious adverse event counts alongside the numbers at risk for three safety groups. In the ranibizumab 0.5 mg group, 11 serious adverse events are listed among 190 at risk. In the sham with ranibizumab 0.5 mg group, 5 are listed among 56 at risk. In the sham without ranibizumab 0.5 mg group, 1 is listed among 5 at risk. The groups are presented separately; the record does not explain how participants were assigned to the two sham safety categories or provide further exposure details.

For other adverse events, the record lists 96 among 190 at risk in the ranibizumab group, 32 among 56 at risk in the sham with ranibizumab group, and 3 among 5 at risk in the sham without ranibizumab group. These counts should be read with their listed denominators and group labels, not as directly comparable risks without accounting for differences in exposure and follow-up.

Macular fibrosis is listed among the serious adverse event terms with 20.0%; acute myocardial infarction, left ventricular dysfunction, angle closure glaucoma, wrist fracture, and diabetes mellitus are each listed with 1.8%. The record does not give further detail about the denominator or group attribution for these percentages. Death counts are not reported in the registry record. These figures describe reported events and are not, on their own, evidence that an event was caused by a study intervention.

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

The posted results describe an average change in BCVA over the primary period and a difference between randomized groups. The ranibizumab group had a higher mean change than the sham group, and the unadjusted recalculation estimates the size and uncertainty of that group difference. The registry’s own reported test also gives p < 0.001. These statistics characterize the trial results; they do not, by themselves, establish what an individual participant will experience.

A statistically small p-value does not determine whether a difference matters to patients. The record does not state a threshold for a clinically important change in BCVA, and the summary does not provide the distribution of individual outcomes. It is therefore not possible to determine from the group means alone how many participants experienced changes of particular importance or how consistently the result was shared across participants.

The primary result addresses the specified average change through Month 3. It does not answer every question about vision, quality of life, durability, safety, or outcomes beyond the reported follow-up. The registry lists secondary measures in those broader areas, but numerical results for most of the listed measures are not reported in the registry record. The later BCVA summary also has to be interpreted in light of the sham arm’s described transition to ranibizumab from Month 3.

The analysis concerns the randomized groups and the Full Analysis Set as described in the record. It does not establish that the posted summary fully resolves the effects of missing observations, treatment received after assignment, or differences in individual follow-up. Detailed information about these issues is not reported in the registry record.

General interpretation: a trial estimate is evidence about the outcomes measured in the study population under the conditions of the study. It should not be stretched into a claim about every patient, every care setting, or every outcome. The posted statistics support a precise description of the observed comparison, while questions about clinical importance and broader applicability require information beyond the reported means and test results.

18. Why This Trial Matters Statistically

This trial illustrates the distinction between a primary endpoint, a registry-reported hypothesis test, and an unadjusted recalculation from summary statistics. The continuous BCVA endpoint retains the scale of change in letters. The mean difference gives a directly scaled contrast, while the standard deviations describe variation among participants and the interval communicates uncertainty about the recalculated contrast.

It also shows why analysis methods should be reported alongside p-values. The registry names a Cochran-Mantel-Haenszel analysis and reports p < 0.001, while the available group summaries permit an unadjusted comparison of means. Those methods can answer related questions, but they are not interchangeable. Without the sponsor estimate, interval, and model details, a reader cannot fully reconcile the analyses or assess adjustments made in the reported test.

The time structure matters as well. The primary measure averages monthly assessments from Month 1 to Month 3, whereas the later BCVA summary extends to Month 12. The sham arm description includes ranibizumab beginning as of Month 3, so a later between-group summary has to be understood in the context of that treatment history. Endpoint timing and intervention history are part of the statistical interpretation, not merely administrative details.

Finally, the record demonstrates the limits of a statistically clear comparison when details about multiplicity, missingness, and the original planning assumptions are absent. A small p-value does not settle those design and reporting questions. Careful interpretation separates what the estimates show from what the registry does not report.

19. 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 sham arm description states that ranibizumab PRN injections began as of Month 3. This complicates interpretation of follow-up beyond that point because the later comparison does not represent an unchanged sham group throughout the full study period. The registry does not provide sufficient detail to characterize the treatment received by each group at each visit or to isolate the effect of that transition.

The posted primary summary provides group means, standard deviations, a recalculated mean difference and interval, and p-values, but the confidence level for the interval is not reported. The sponsor analysis has a named method and p-value but no estimate, interval, or implementation details. The unadjusted recalculation should therefore not be mistaken for a full reproduction of the sponsor’s analysis.

The record does not report the original sample-size assumptions, the complete statistical analysis plan, multiplicity handling, interim analyses, or stopping rules. The Full Analysis Set is described, but endpoint-specific missingness counts and detailed imputation rules are not reported. The population description’s MV-LOCF expansion is incomplete, and sensitivity analyses are not reported in the registry record.

Numerical secondary results are limited in the record. Although multiple secondary outcomes are listed, the posted numerical summary does not permit a broad assessment of outcomes such as central-sub-field thickness, categorized letter changes, or NEI-VFQ-25 scores. The safety record also separates the sham group according to ranibizumab exposure but does not provide fuller information about exposure timing, follow-up, or attribution for the listed event-term percentages.

These reporting limitations do not negate the posted results, but they narrow what can be concluded from them. Generalizability beyond the registry’s stated population and study conditions is not established by these summaries.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Central Retinal Vein Occlusion (CRVO) — NCT01976312.
• Registry record last updated 2017-05-30; status last verified 2017-04.
• Results first posted 2017-04-24.
• 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.

23. Record Summary

The registry describes a completed randomized, double-masked, parallel-group Phase III study of ranibizumab 0.5 mg versus sham injection in patients with visual impairment due to macular edema secondary to CRVO. Enrollment is listed as 252. The primary endpoint is average change in BCVA letters from baseline to Month 1 through Month 3.

The primary group means were 11.3 letters for ranibizumab and -2.7 letters for sham. The unadjusted recalculated mean difference is 14.0 letters, with an interval from 10.21 to 17.79 and p < 0.001. The registry-reported Cochran-Mantel-Haenszel analysis also reports p < 0.001, without an estimate or interval.

The sham arm description includes ranibizumab PRN injections from Month 3. The registry lists additional secondary and safety outcomes, but many numerical results and key analysis details are not reported in the registry record.