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 Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (NCT03917472), a randomized phase 3 study. The primary outcome is Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03917472 |
| Phase | Phase 3 |
| Condition | Diabetic Macular Edema |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 517 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants had visual impairment due to diabetic macular edema. The primary analysis used the full analysis set with last observation carried forward for missing values. The registry describes eligible study-eye baseline visual acuity scores from 73 to 23 ETDRS letters, approximately equivalent to Snellen acuity from 20/40 to 20/320.
Intervention
Brolucizumab 6 mg/0.05 mL was administered every 4 weeks. The primary question concerns the change in best-corrected visual acuity in the study eye from baseline to Week 52.
Comparator
Aflibercept 2 mg/0.05 mL was administered every 4 weeks. The trial compared the Week 52 visual-acuity outcome between the brolucizumab and aflibercept groups.
Primary question
How did mean change in study-eye best-corrected visual acuity at Week 52 compare between the randomized groups? The registry also reports a superiority analysis and a non-inferiority analysis. The non-inferiority margin and its justification are not reported in the registry record, so the non-inferiority result cannot be fully assessed from the posted information alone.
The clinical focus was visual function, measured using Early Treatment Diabetic Retinopathy Study visual-acuity charts. A higher ETDRS letter score represents better functioning. The primary endpoint therefore concerns change in a scored measure of vision rather than a direct measure of retinal anatomy or fluid. The registry also lists anatomical and fluid-related outcomes, along with safety outcomes, but these address different aspects of the study and should not be treated as interchangeable with the primary visual-acuity endpoint.
3. Trial Design
KINGFISHER was a phase III, randomized, parallel-group study of brolucizumab and aflibercept in participants with visual impairment due to diabetic macular edema. The official title describes a 12-month, 2-arm, randomized, double-masked, multicenter study. The registry’s masking field is recorded as triple. The record does not explain this difference in masking terminology. The trial status is completed.
The registry records enrollment of 517 participants. The primary outcome lists 346 participants in the brolucizumab group and 171 in the aflibercept group. The interventions were brolucizumab 6 mg/0.05 mL every 4 weeks and aflibercept 2 mg/0.05 mL every 4 weeks. The primary endpoint was change from baseline in study-eye best-corrected visual acuity at Week 52. The registry identifies the analysis population as the full analysis set and states that last observation carried forward was used to impute missing values.
The recorded study start date is 2019-07-17, and the primary completion date is 2021-03-24. The record identifies Novartis Pharmaceuticals as sponsor. Additional details about the randomization procedure, allocation concealment, participating sites, adherence, protocol deviations, or the rationale for the planned enrollment are not reported in the registry record. The registry also does not report the statistical-analysis plan in enough detail to establish how all analyses were prespecified or how the reported masking labels relate to one another.
The study compared active treatments, rather than comparing an active treatment with no treatment. Consequently, the primary contrast addresses relative outcomes between the two randomized groups under the recorded regimens. It does not, by itself, establish the absolute effect of either intervention compared with no treatment. The trial’s duration and endpoint timing also mean that its primary visual-acuity result concerns the Week 52 assessment, not outcomes beyond the study period recorded in the registry.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 48). For all subjects, the last study assessment was performed at the Week 52/end of study (EOS) visit. All subjects had study visits q4w through Week 52. The primary analysis was performed at the EOS visit (Week 52).
Overall Study
| Stage | Brolucizumab 6mg q4w | Aflibercept 2mg q4w |
|---|---|---|
| STARTED | 346 | 171 |
| COMPLETED | 311 | 156 |
| NOT COMPLETED | 35 | 15 |
Reasons for not completing this period:
| Reason | Brolucizumab 6mg q4w | Aflibercept 2mg q4w |
|---|---|---|
| Physician Decision | 4 | 0 |
| Adverse Event | 3 | 1 |
| Death | 7 | 5 |
| Withdrawal by Subject | 11 | 4 |
| Lost to Follow-up | 10 | 5 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) - Last observation carried forward (LOCF)
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 | Brolucizumab 6mg q4w | Aflibercept 2mg q4w | Total |
|---|---|---|---|---|
| Participants analysed | 346 | 171 | 517 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 208 | 115 | 323 |
| Age, Categorical: >=65 years | Participants | 138 | 56 | 194 |
| Age, Continuous | years | 60.9 (SD 10.59) | 60.2 (SD 9.31) | 60.7 (SD 10.18) |
| Sex: Female, Male: Female | Participants | 152 | 66 | 218 |
| Sex: Female, Male: Male | Participants | 194 | 105 | 299 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 14 | 7 | 21 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 40 | 15 | 55 |
| Race (NIH/OMB): White | Participants | 288 | 145 | 433 |
| Race (NIH/OMB): More than one race | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 3 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52, measured over Baseline, Week 52.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Scores on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in best-corrected visual acuity in the study eye at Week 52. Visual acuity was assessed with Early Treatment Diabetic Retinopathy Study charts and recorded as a letter score. The registry states that possible scores ranged from 0 to 100 and that a higher score represents better visual functioning. The eligibility range is recorded as 73 to 23 letters, with an approximate Snellen equivalent of 20/40 to 20/320.
Visual acuity is used because it directly quantifies a component of visual function that is relevant to the study population. A change-from-baseline endpoint compares the Week 52 score with the participant’s baseline score, focusing the analysis on change during the study rather than only the final score. The registry reports group least-squares means and a between-group least-squares mean difference, with a 95% confidence interval.
This endpoint is distinct from measures of retinal thickness, fluid, or absence of diabetic macular edema. Those outcomes can provide information about retinal structure or disease features, but they do not replace the visual-acuity endpoint. The registry states that last observation carried forward was used for missing primary endpoint values. The details of how missingness was handled in sensitivity analyses, if any, are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported Week 52 least-squares mean change was 12.2 for brolucizumab and 11.0 for aflibercept. The reported between-group least-squares mean difference was 1.1, with a 95% confidence interval from -0.6 to 2.9 and p = 0.099 for superiority. The confidence interval includes zero, so the posted estimate is compatible with no between-group difference as well as with differences in either direction within the interval. The p-value does not provide strong evidence against the no-difference hypothesis under the reported superiority analysis. It should not be read as proof that the groups were identical or that a difference is impossible.
The registry separately reports a non-inferiority analysis with p < 0.001. That result is labelled as a non-inferiority test, but the margin, the confidence-interval criterion, and the analysis details needed to judge the test are not reported in the registry record. A small p-value by itself does not reveal the size or clinical meaning of the allowed difference. The non-inferiority result therefore cannot be independently interpreted fully from the available record.
The primary estimate is a comparison of group means, not a statement about every participant’s response. A mean can conceal variation among participants, and the confidence interval describes uncertainty in the group contrast rather than the range of individual changes. It is also important that the outcome is a change score analyzed using least-squares means; the registry does not give further model details in the record.
The numerical result should be read within its stated context: the full analysis set, last observation carried forward for missing values, the study-eye measure, and the Week 52 timeframe. It does not establish how the groups compare at other time points or beyond the recorded study period. Nor does the result alone determine whether a difference of a particular size matters to patients; a threshold for clinical importance is not reported in the registry record.
Overall, the posted superiority analysis estimates a modest positive between-group difference, but its confidence interval spans zero and its p-value is 0.099. The separate non-inferiority label is accompanied by a p-value but not enough information to evaluate the margin or the full test. These are distinct statistical questions and should not be collapsed into a single claim about the trial’s conclusion.
9. Statistical Methods Explained
The registry reports an analysis of a continuous endpoint: change in ETDRS visual-acuity score from baseline to Week 52. It presents least-squares means for each group and a least-squares mean difference for the comparison. A least-squares mean is a model-based group estimate. It can differ from a simple arithmetic mean when the analysis model adjusts for factors or uses a particular model structure. The registry identifies ANOVA for the reported comparison, but further details of the model and any adjustment variables are not reported in the registry record.
What does the confidence interval say?
The reported 95% confidence interval for the between-group difference is -0.6 to 2.9. In general, a confidence interval expresses the uncertainty around an estimate under the analysis assumptions: intervals that are wider indicate less precision than narrower intervals. The interval includes zero, the value corresponding to no difference between group means. It therefore does not rule out no difference under the reported model. The interval also includes values on either side of zero, so the posted estimate is not precise enough to establish the direction of the underlying difference with confidence at this interval level.
A confidence interval is not a range containing most individual participants’ changes. It concerns uncertainty in the estimated group contrast. It also does not, by itself, determine whether a difference is clinically important. The registry does not report a clinical-importance threshold for this endpoint.
How should the superiority test be read?
The registry reports an ANOVA superiority comparison with a least-squares mean difference of 1.1, a 95% confidence interval from -0.6 to 2.9, and p = 0.099. A p-value describes how unusual data at least as incompatible with the null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, nor is it a measure of the probability that the result will replicate. Here, the p-value and interval both indicate that the posted superiority analysis does not resolve whether there is a between-group difference. The registry’s threshold for declaring superiority is not reported in the registry record, so the statistical interpretation should stay with the estimate, interval, and p-value rather than assume a decision rule.
What does a non-inferiority test require?
In general, a non-inferiority test asks whether the outcome with one intervention is not worse than the comparator by more than a prespecified margin. The margin is central: it defines the largest difference that the study is intended to rule out. The registry reports p < 0.001 for a non-inferiority analysis, but does not report the margin, its rationale, the corresponding estimate and interval, or enough detail to reconstruct the decision rule. The result can therefore be described as the registry’s reported non-inferiority finding, but it cannot be independently evaluated in full from the posted record.
What does over-dispersion mean?
Over-dispersion is a general concern for count outcomes when observed variability exceeds what a statistical model assumes. When it is present and not handled appropriately, standard errors and confidence intervals can be unreliable. The primary endpoint in this trial is continuous, and the registry identifies ANOVA for its reported comparison. Details about model diagnostics or dispersion assessments are not reported in the registry record. The concept is more relevant to some count or event outcomes than to interpreting the primary mean difference as posted.
How should the planning illustrations be used?
The planning illustrations are based on the observed risk difference for non-ocular adverse events, not on the primary visual-acuity endpoint. The assumptions state a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. For planning for 100% of the observed effect, the illustration gives 2,098 participants per arm for 80% power and 2,809 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 3,717 participants per arm for 80% power and 4,975 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 8,331 participants per arm for 80% power and 11,152 participants per arm for 90% power.
These are planning illustrations computed from an observed effect; they are not the trial’s own design justification and are not observed power. They do not establish the probability that the completed study detected an effect, and they do not show what enrollment was required under the trial’s original assumptions. The trial’s own sample-size assumptions and justification are not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANOVA | LS mean difference 1.1 | -0.6 to 2.9 | 0.099 |
| ANOVA | not reported | < 0.001 |
The registry reports the sponsor-associated primary analysis as an ANOVA comparison of least-squares means. For superiority, the reported difference is 1.1, with a 95% confidence interval from -0.6 to 2.9 and p = 0.099. The group least-squares means are 12.2 for brolucizumab and 11.0 for aflibercept. These are the posted trial-analysis results and should be distinguished from any recalculation based on summary data.
No recalculated primary comparison is reported in the registry record. The registry entries therefore do not establish an independent recalculated primary estimate to compare with the sponsor’s analysis. The posted comparison uses ANOVA and least-squares means, while a simple recalculation from group summaries would not necessarily reproduce a model-based analysis, particularly when model details are absent. No discrepancy between a recalculated primary analysis and the reported analysis is recorded.
The registry also reports a non-inferiority p-value of < 0.001, but does not provide the margin or enough associated statistical detail for an independent assessment. The sponsor’s reported result can be stated as recorded, while the missing margin and model information limit interpretation. The superiority and non-inferiority analyses address different hypotheses and should be considered separately.
11. Multiplicity, Missing Data and Analysis Populations
The registry records multiple outcomes and analyses, including a primary visual-acuity endpoint, secondary anatomical and visual outcomes, and safety outcomes. It does not report a multiplicity-adjustment strategy or explain how the statistical testing hierarchy was organized. When many outcomes or comparisons are tested, the chance of at least one apparently positive result can increase. In general, prespecified testing sequences or multiplicity adjustments can address that issue, but whether either approach was used in this trial is not reported in the registry record. Unadjusted secondary results, if considered, therefore warrant more caution than a result protected by a clearly stated testing plan.
Missing primary outcome values were handled using last observation carried forward in the full analysis set. This method carries a participant’s last recorded value forward to represent a later missing assessment. In general, that approach relies on assumptions about how the outcome would have changed after the last observation; those assumptions may not match the actual course of the measure. The registry does not report the amount or pattern of missing Week 52 data, reasons for missingness, or sensitivity analyses examining alternative missing-data assumptions. The impact of the imputation choice therefore cannot be assessed from the posted record alone.
The registry identifies the primary population as the full analysis set, but further details of the population definition and exclusions are not reported in the registry record. It also does not report whether the non-inferiority analysis used a separate population or how any protocol deviations were handled. These details matter because the analysis population and missing-data approach can affect interpretation, particularly for non-inferiority questions.
The non-inferiority margin, its clinical rationale, the complete analysis plan, and the approach to interim analyses are not reported in the registry record. No assumptions about these features can be made from the posted results. The record also does not provide enough information to determine whether all secondary outcomes were prespecified or how their results were intended to be interpreted alongside the primary endpoint.
12. 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 |
|---|---|---|---|
| Brolucizumab 6mg | 74 | 346 | 21.4% |
| Aflibercept 2mg | 36 | 171 | 21.1% |
| Overall | 110 | 517 | 21.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Brolucizumab 6mg | 7 of 346 |
| Aflibercept 2mg | 5 of 171 |
| Overall | 12 of 517 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Brolucizumab 6mg | 144 of 346 |
| Aflibercept 2mg | 92 of 171 |
| Overall | 236 of 517 |
Most frequent serious adverse event terms
| Event term | Organ system | Brolucizumab 6mg | Aflibercept 2mg | Overall |
|---|---|---|---|---|
| Cerebrovascular accident | Nervous system disorders | 6 of 346 | 6 of 171 | 12 of 517 |
| COVID-19 | Infections and infestations | 8 of 346 | 1 of 171 | 9 of 517 |
| Osteomyelitis | Infections and infestations | 3 of 346 | 2 of 171 | 5 of 517 |
| Pneumonia | Infections and infestations | 3 of 346 | 2 of 171 | 5 of 517 |
| Acute kidney injury | Renal and urinary disorders | 4 of 346 | 1 of 171 | 5 of 517 |
| Cardiac failure | Cardiac disorders | 3 of 346 | 1 of 171 | 4 of 517 |
| Cardiac failure congestive | Cardiac disorders | 4 of 346 | 0 of 171 | 4 of 517 |
| Coronary artery disease | Cardiac disorders | 3 of 346 | 1 of 171 | 4 of 517 |
| Myocardial infarction | Cardiac disorders | 3 of 346 | 1 of 171 | 4 of 517 |
| COVID-19 pneumonia | Infections and infestations | 4 of 346 | 0 of 171 | 4 of 517 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Brolucizumab 6mg | Aflibercept 2mg | Overall |
|---|---|---|---|---|
| Hypertension | Vascular disorders | 18 of 346 | 13 of 171 | 31 of 517 |
| COVID-19 | Infections and infestations | 11 of 346 | 11 of 171 | 22 of 517 |
| Diabetic retinal oedema - Fellow eye | Eye disorders | 10 of 346 | 7 of 171 | 17 of 517 |
| Vitreous detachment - Study eye | Eye disorders | 10 of 346 | 7 of 171 | 17 of 517 |
| Conjunctival haemorrhage - Study eye | Eye disorders | 9 of 346 | 7 of 171 | 16 of 517 |
| Cataract - Study eye | Eye disorders | 9 of 346 | 6 of 171 | 15 of 517 |
| Vitreous haemorrhage - Fellow eye | Eye disorders | 10 of 346 | 4 of 171 | 14 of 517 |
| Nasopharyngitis | Infections and infestations | 8 of 346 | 6 of 171 | 14 of 517 |
| Vitreous floaters - Study eye | Eye disorders | 8 of 346 | 5 of 171 | 13 of 517 |
| Urinary tract infection | Infections and infestations | 11 of 346 | 2 of 171 | 13 of 517 |
Serious events with the highest arm-level rate: cerebrovascular accident (3.5%), covid-19 (2.3%), diabetic foot infection (1.2%), osteomyelitis (1.2%), pneumonia (1.2%).
The registry reports serious adverse events among 74 of 346 participants at risk in the brolucizumab group and 36 of 171 at risk in the aflibercept group. The overall figures are 110 of 517 at risk. Deaths are recorded as 7 in the brolucizumab group, 5 in the aflibercept group, and 12 overall. These are counts reported by the registry; they do not establish that an event was caused by study treatment.
The registry lists cerebrovascular accident at 3.5%, COVID-19 at 2.3%, and diabetic foot infection, osteomyelitis, pneumonia, and hypertension at 1.2% each among the top serious-event terms. The event terms and percentages describe reported safety findings, not a causal comparison between groups. The record does not provide a detailed event-by-event assessment of causality or enough information in these figures alone to assess differences in severity, timing, or clinical context.
In general, safety counts should be read with their denominators, the observation period, and the way events were defined in mind. Non-ocular adverse events were reported from the first dose until the end of study treatment plus 30 days post-treatment, up to a maximum duration of approximately 52 weeks. The posted figures support description of reported events during that period; they do not by themselves establish comparative risk or causation.
13. What the Result Does, and Does Not, Mean
The primary result describes average change in study-eye visual-acuity scores at Week 52 among participants in the full analysis set, using the registry’s last-observation-carried-forward approach. The reported mean difference is 1.1, and its 95% confidence interval extends from -0.6 to 2.9. This conveys both the direction of the point estimate and the uncertainty around it. Because the interval includes zero, the analysis does not establish a clear between-group difference in the superiority comparison.
That interpretation is not equivalent to saying the treatments are identical. Failure to establish superiority does not prove equivalence, and the interval remains compatible with differences in either direction. Equivalence would require an appropriate prespecified margin and a corresponding analysis; such a margin is not reported in the registry record. Similarly, the reported non-inferiority p-value cannot be taken as a complete demonstration without the margin and analysis details.
The result also does not describe individual participants’ outcomes. It is a comparison of group-level model estimates, and the registry’s summary does not show how outcomes varied across participants. Nor does the primary result settle the findings for anatomical outcomes, fluid status, or adverse events. Numerical results for the listed visual and anatomical secondary outcomes are not reported in the registry record.
Finally, the finding is tied to the recorded study population, treatment schedules, endpoint, analysis population, missing-data method, and Week 52 timeframe. It should not be extended automatically to other populations, other regimens, other time points, or outcomes not measured in the primary analysis. The posted data support a precise description of the trial’s recorded estimates and their uncertainty, not medical advice or a universal conclusion about treatment.
14. Why This Trial Matters Statistically
This trial is statistically informative because it reports both a continuous primary endpoint and separate superiority and non-inferiority analyses. Those analyses ask different questions. The superiority comparison estimates a mean difference and reports its confidence interval, making the uncertainty around the Week 52 contrast visible. The non-inferiority result is also posted, but its interpretation depends critically on a margin that is not reported in the registry record.
The case also illustrates why a point estimate should not be read in isolation. The reported least-squares mean difference is 1.1, while the confidence interval ranges from -0.6 to 2.9. The interval communicates that the data do not pin down the direction of the underlying difference with precision. The p-value of 0.099 complements that interval but does not replace it or express the probability that a treatment effect is real.
Another important statistical issue is missing-data handling. The registry states that last observation carried forward was used for the primary analysis, but does not report missingness patterns or sensitivity analyses. Those details are essential for understanding how robust the result is to assumptions about participants with unobserved Week 52 outcomes. Likewise, the registry lists numerous secondary outcomes, but does not describe a multiplicity strategy or post numerical findings for the listed visual and anatomical outcomes.
The record therefore provides a useful example of the distinction between a reported result and a fully assessable analysis. Clear estimates and intervals are valuable, but interpretation also depends on the analysis plan, missing-data assumptions, multiplicity control, and non-inferiority margin. Where those details are absent, statistical conclusions should remain appropriately bounded.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several trial-specific limitations of interpretation arise from what the registry record reports. The primary superiority result is accompanied by an estimate, confidence interval, and p-value, but detailed model specifications and adjustment variables are not reported in the registry record. The non-inferiority analysis is less completely described: the margin, rationale, estimate, and interval are not reported. This prevents independent evaluation of the non-inferiority criterion.
The primary analysis used last observation carried forward, yet the record does not give the amount or pattern of missing outcome data or report sensitivity analyses. Without that information, it is not possible to judge how strongly the primary result depends on the imputation assumption. The full analysis set is named, but the record does not fully describe its membership or how deviations from the planned treatment and assessments were handled.
The registry lists multiple secondary outcomes, but numerical findings for the visual and anatomical outcomes are not reported in the record. The multiplicity strategy is also not reported. These gaps limit the ability to evaluate whether secondary findings are consistent with the primary comparison or how any secondary p-values should be interpreted.
The official title calls the study double-masked, while the registry masking field says triple. The record does not explain the difference. The registry also does not report details about the randomization procedure, allocation concealment, or the sample-size rationale. These limitations do not erase the posted results, but they constrain how fully the trial’s conduct and statistical analysis can be assessed from the registry record alone.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema — NCT03917472.
- Registry record last updated 2022-08-12; status last verified 2022-08.
- Results first posted 2022-04-21.
- 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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19. Record Summary
KINGFISHER (NCT03917472) is a completed, randomized, parallel-group phase III study of brolucizumab versus aflibercept for visual impairment due to diabetic macular edema. The registry records enrollment of 517 participants and identifies Novartis Pharmaceuticals as sponsor. The recorded study start date is 2019-07-17 and primary completion date is 2021-03-24.
The primary outcome was change from baseline in study-eye best-corrected visual acuity at Week 52. The reported superiority comparison gives a least-squares mean difference of 1.1, with a 95% confidence interval from -0.6 to 2.9 and p = 0.099. A non-inferiority p-value of < 0.001 is also reported, but the margin and associated details are not reported in the registry record. The primary analysis used the full analysis set and last observation carried forward for missing values.
The record lists additional visual, anatomical, and safety outcomes. Important details about multiplicity, missing-data sensitivity analyses, and the full non-inferiority analysis are not reported in the registry record, limiting independent assessment of those aspects.