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 of Aliskiren in the Treatment of Diabetic Macular Edema (NCT00768040), a randomized phase 2 study. The primary outcome is Change From Baseline in Central Retinal Thickness in Patients With Type 1 or Type 2 Diabetes, After 12 Weeks of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00768040 |
| Phase | Phase 2 |
| Condition | Diabetic Macular Edema |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 39 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
The study asked whether adding oral aliskiren to care for people with diabetic macular edema was associated with a change in central retinal thickness over 12 weeks, compared with matching placebo. Participants had type 1 or type 2 diabetes. The registry describes the study as a randomized, double-masked, placebo-controlled add-on study; it also records triple masking.
Population
Participants with diabetic macular edema and type 1 or type 2 diabetes. The study enrolled 39 participants and was terminated early because of low recruitment.
Intervention
Aliskiren 300 mg once daily for 12 weeks. The official title describes oral aliskiren as an add-on treatment, but the registry record does not report the background treatments participants received.
Comparator
Matching placebo once daily for 12 weeks.
Primary question
How did central retinal thickness change from baseline to week 12 in the aliskiren group compared with the placebo group? The registry record does not report the estimated changes or the between-group comparison.
Central retinal thickness was measured using optical coherence tomography. The registered outcome concerns a change in a continuous measurement, rather than a count of people who did or did not meet a response threshold. The registry specifies an adjusted analysis that accounts for the baseline measurement, but does not report the numerical results of that analysis. Consequently, the posted record does not establish the size or precision of any difference between groups.
3. Trial Design
This was a phase 2, randomized, parallel-group study of aliskiren and placebo for diabetic macular edema. The registry lists 39 participants enrolled. It records the study status as terminated and states that the study ended early because of low recruitment of patients. The registry records a start date of 2008-09 and primary completion of 2011-02.
Participants were assigned to aliskiren 300 mg once daily or matching placebo once daily, with both regimens described as lasting 12 weeks. The official title characterizes the study as an add-on study. Details of background treatment, eligibility criteria beyond the stated condition and diabetes types, and how randomization was implemented are not reported in the registry record.
The record describes the study as randomized, double-masked and placebo-controlled, and separately identifies the masking as triple. It does not identify which participant or study roles were masked, or explain how masking was maintained. The parallel-group model means the design compared groups assigned to different study regimens rather than describing a crossover between regimens.
Early termination due to low recruitment is important context for interpreting the evidence. It does not, by itself, reveal the direction or size of the treatment comparison. The registry does not report the planned enrollment target, the reason recruitment was low, or whether other operational issues contributed to termination. Those details are not reported in the registry record.
Although the study has a registered primary outcome and an analysis description, numerical outcome estimates are not reported in the registry record. Therefore the design can be described, but the record does not permit a numerical account of the primary comparison. It also does not provide enough information to assess how closely the completed study followed its original plans.
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.
Overall Study
| Stage | Aliskiren 300 mg | Placebo |
|---|---|---|
| STARTED | 20 | 19 |
| COMPLETED | 16 | 16 |
| NOT COMPLETED | 4 | 3 |
Reasons for not completing this period:
| Reason | Aliskiren 300 mg | Placebo |
|---|---|---|
| Adverse Event | 3 | 2 |
| Abnormal laboratory value | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: This study was terminated early due to low recruitment of patients.
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 | Aliskiren 300 mg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 19 | 39 | |
| Age Continuous | years | 64.3 (SD 10.76) | 60.1 (SD 10.57) | 62.2 (SD 10.74) |
| Age, Customized: 18 - 64 years | participants | 9 | 13 | 22 |
| Age, Customized: 65 - 84 years | participants | 11 | 6 | 17 |
| Sex: Female, Male: Female | Participants | 7 | 4 | 11 |
| Sex: Female, Male: Male | Participants | 13 | 15 | 28 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Central Retinal Thickness in Patients With Type 1 or Type 2 Diabetes, After 12 Weeks of Treatment, measured over Baseline to week 12.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | μm |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in central retinal thickness at week 12, measured in μm using optical coherence tomography. Central retinal thickness is a continuous measurement of retinal structure. Analyzing change from baseline focuses the comparison on how the measured thickness shifted during the treatment period, rather than on the final measurement alone.
The registry describes the outcome as a least-squares mean and specifies standard error as the measure of dispersion. It states that changes were analyzed with a univariate analysis of covariance model, including baseline value as a covariate and treatment as a fixed factor. In general, adjusting for a baseline measurement can account for starting differences in the outcome when estimating the treatment-group comparison. The posted record does not report the group estimates, the adjusted contrast, or its uncertainty.
This endpoint addresses a measured structural outcome over the specified treatment period. It does not, on its own, describe symptoms, vision-related functioning, or longer-term outcomes. Those outcomes are not reported as primary measures in the registry record. The registry also does not supply a threshold for what would count as a clinically important change in central retinal thickness. Without the outcome estimates and a stated interpretive threshold, the record cannot establish the magnitude or practical significance of the observed change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies central retinal thickness change from baseline to week 12 as the primary outcome and describes an adjusted comparison between aliskiren and placebo. However, it does not report the numerical results for that outcome. In particular, the record contains no posted least-squares mean changes, standard errors, treatment contrast, confidence interval, or p-value. The direction and magnitude of the primary comparison therefore cannot be determined from the registry record.
The study enrolled 39 participants and was terminated early because of low recruitment. That context matters when considering how much information the study could provide, but it cannot substitute for the missing outcome estimates. A small or prematurely terminated study may leave substantial uncertainty, yet the extent of uncertainty cannot be quantified without the estimated effect and its precision. It would be inappropriate to infer an effect from the enrollment count or from the fact that an analysis method is described.
The registry lists one outcome measure and no analysis records. This means the posted record does not provide a numerical analysis to inspect; it does not show that no analysis was ever conducted. The detailed statistical analysis plan, whether any interim analyses took place, and the handling of deviations from the intended analysis are not reported in the registry record.
The adverse-event entries provide some safety counts for the two groups, but they do not fill the gap in the primary efficacy results. The record lists serious adverse events affecting 2 of 20 participants at risk in the aliskiren group and 2 of 19 at risk in the placebo group. Other adverse events are listed as affecting 13 of 20 and 9 of 19, respectively. These counts should be read as descriptive entries in the registry, not as a complete comparison of safety or as a basis for drawing conclusions about treatment effects. Deaths are not reported in the registry record.
Any sample-size figures based on the observed effect are planning illustrations, not observed power. The stated assumptions describe two-sided significance level 0.05, equal allocation, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Since the primary effect estimate is not reported in the registry record, such illustrations should not be mistaken for a substitute for the trial’s outcome estimates or for evidence about the result.
Overall, the record documents the question, design, endpoint and reason for early termination, but leaves the primary statistical result unavailable. It supports a description of what the trial intended to compare, not a conclusion about the direction, size or precision of the treatment-group difference.
9. Statistical Methods Explained
The registry specifies an analysis approach for a continuous endpoint: change in central retinal thickness from baseline to week 12. It describes the endpoint estimate as a least-squares mean, identifies standard error as the dispersion measure, and names a univariate analysis of covariance model with baseline value as a covariate and treatment as a fixed factor. The numerical output from that model is not reported in the registry record.
What does an ANCOVA do?
General statistical explanation: analysis of covariance, or ANCOVA, models an outcome while accounting for a covariate. In this study’s registered description, the outcome is change in central retinal thickness, the baseline measurement is the covariate, and treatment group is a fixed factor. Adjusting for baseline can help distinguish the treatment-group comparison from variation related to where participants started. It does not guarantee that groups were identical at baseline, nor does it remove uncertainty from an incomplete or small dataset.
The registry calls the reported group estimate a least-squares mean. General explanation: a least-squares mean is a model-based mean estimated after accounting for terms included in the model. Here, the described model includes baseline and treatment. It is not necessarily identical to a simple arithmetic average of observed changes. Since the estimates are not posted, readers cannot compare model-based values with raw group summaries or assess the size of any adjustment.
How should standard error be understood?
General statistical explanation: a standard error describes the sampling uncertainty of an estimate under the statistical model; it is not the spread of individual participants’ measurements. A standard error can be used in forming a confidence interval when the estimate and relevant modeling details are available. The registry names standard error as the dispersion measure, but does not report the values. Therefore neither the precision of the group estimates nor the precision of the treatment contrast can be evaluated from the posted record.
General statistical explanation: a confidence interval gives a range of values compatible with the data and analysis under the method’s assumptions. Its width reflects uncertainty, and it should be interpreted alongside the estimated effect and the clinical context. No confidence interval for the primary comparison is reported in the registry record. A p-value, even if available, would not by itself show the size or practical importance of an effect; no primary-outcome p-value is reported either.
Why does the outcome’s continuous scale matter?
General statistical explanation: a continuous endpoint retains information about the degree of change, rather than reducing each participant to a yes-or-no category. That can be useful when the measurement is meaningful across its range. Interpretation still depends on the measurement process, the distribution of values, and whether a difference of a given size matters. The registry identifies optical coherence tomography as the measurement method but does not report a threshold for a meaningful change or detailed information about measurement quality.
The registry’s description is univariate, naming a single outcome model with baseline and treatment terms. It does not specify additional covariates, diagnostics, transformations, or procedures for checking model assumptions. Those details are not reported in the registry record. General statistical explanation: model-based comparisons rely on assumptions about the relationship between the outcome and covariates and about the behavior of model errors. Without diagnostic information or the underlying results, those assumptions cannot be evaluated from this record.
What can planning calculations tell readers?
The stated sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These calculations are planning illustrations, not observed power. General statistical explanation: sample-size planning estimates how much information a future study might need under selected assumptions; it does not measure the probability that the completed trial has demonstrated an effect. Any such illustration depends on the effect estimate and assumptions used. The primary effect estimate is not reported in the registry record, so those planning figures should not be treated as a substitute for a reported trial result.
The registry does not report the trial’s original sample-size justification, target enrollment, or detailed statistical analysis plan. It also does not report whether an interim analysis was planned or conducted. No inference about these design choices can be made from the model description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure, change from baseline in central retinal thickness at week 12. It records no analysis entries, and numerical results for the primary outcome are not reported in the registry record. The record therefore does not allow an assessment of how many statistical comparisons were performed or which analysis was designated as primary in a detailed analysis plan.
Multiplicity concerns arise when multiple outcomes, time points, groups or analyses create several opportunities to obtain apparently notable results. General statistical explanation: a prespecified strategy for handling multiple comparisons can help control the chance of misleading findings when many tests are performed. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a broader testing strategy. It also does not report interim analyses or stopping rules; these should not be assumed from the early termination entry, which is attributed to low recruitment.
The handling of missing outcome measurements is not reported in the registry record. Details such as the analysis population, inclusion rules, imputation, sensitivity analyses and treatment of participants who did not complete the intended follow-up are also not reported. The early termination means the study ended before the planned 12-week treatment description could be interpreted as proof that every enrolled participant had a week-12 measurement. The number with observed endpoint data is not reported in the registry record.
These omissions limit reproducibility and make it difficult to judge whether the reported statistical approach, if used, addressed incomplete data or multiple analyses. They do not establish that the investigators failed to conduct such procedures; they mean that the registry record does not describe them.
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 |
|---|---|---|---|
| Aliskiren 300mg | 2 | 20 | 10.0% |
| Placebo | 2 | 19 | 10.5% |
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 |
|---|---|
| Aliskiren 300mg | 13 of 20 |
| Placebo | 9 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Aliskiren 300mg | Placebo |
|---|---|---|---|
| Cellulitis | Infections and infestations | 1 of 20 | 0 of 19 |
| Pneumonia | Infections and infestations | 1 of 20 | 0 of 19 |
| Pneumonia legionella | Infections and infestations | 0 of 20 | 1 of 19 |
| Diabetic foot | Metabolism and nutrition disorders | 1 of 20 | 0 of 19 |
| Cerebrovascular accident | Nervous system disorders | 0 of 20 | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Aliskiren 300mg | Placebo |
|---|---|---|---|
| Dizziness | Nervous system disorders | 2 of 20 | 2 of 19 |
| Headache | Nervous system disorders | 2 of 20 | 2 of 19 |
| Macular oedema | Eye disorders | 1 of 20 | 1 of 19 |
| Vomiting | Gastrointestinal disorders | 0 of 20 | 2 of 19 |
| Seasonal allergy | Immune system disorders | 1 of 20 | 1 of 19 |
| Gastroenteritis viral | Infections and infestations | 1 of 20 | 1 of 19 |
| Urinary tract infection | Infections and infestations | 1 of 20 | 1 of 19 |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 20 | 0 of 19 |
| Hypotension | Vascular disorders | 2 of 20 | 0 of 19 |
| Atrial fibrillation | Cardiac disorders | 0 of 20 | 1 of 19 |
Serious events with the highest arm-level rate: pneumonia legionella (5.3%), cerebrovascular accident (5.3%), cellulitis (5.0%), pneumonia (5.0%), diabetic foot (5.0%).
The registry lists serious adverse events and other adverse events separately for the two groups. In the aliskiren 300mg group, serious adverse events are recorded for 2 of 20 participants at risk, and other adverse events for 13 of 20. In the placebo group, serious adverse events are recorded for 2 of 19 participants at risk, and other adverse events for 9 of 19. These are descriptive counts in the registry and should not be read as a complete assessment of comparative safety.
The record also lists serious-event terms with percentages: Pneumonia legionella, 5.3%; Cerebrovascular accident, 5.3%; Cellulitis, 5.0%; Pneumonia, 5.0%; and Diabetic foot, 5.0%. It does not specify in this listing how the terms are allocated between study groups. The registry record does not report deaths. The listed terms and percentages do not provide the full context needed to interpret event timing, recurrence, severity details beyond the serious-event classification, or possible relationship to treatment.
General statistical explanation: safety counts are most informative when their definitions, follow-up, attribution procedures and denominators are clear and when they are interpreted alongside the study design and duration. The registry specifies participants at risk for each group, but does not report further detail about safety ascertainment. These entries should therefore be treated as a limited descriptive record, not as proof for or against a safety difference.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, placebo-controlled phase 2 study was designed to compare aliskiren 300 mg once daily with matching placebo over 12 weeks in people with diabetic macular edema. It also records the primary endpoint and the intended adjusted analysis. Those details explain what the investigators set out to study.
The posted record does not report the primary outcome estimates. Without the group changes, adjusted contrast and uncertainty, it is not possible to say whether central retinal thickness changed more in one group, how large any difference was, or how precisely it was estimated. The absence of numerical results in the registry record is not evidence that the groups had the same result, and it is not evidence that one group had a better result.
Likewise, early termination due to low recruitment does not determine the outcome. It indicates an important limitation in the study’s completion, but the record does not explain whether other factors affected the conduct or analysis. The enrollment count alone cannot indicate the degree of uncertainty around an unreported effect.
The listed adverse-event counts give limited descriptive information for the enrolled groups. They are not a comprehensive evaluation of safety, and the registry does not report deaths. Nor does the registry provide enough information to assess missing outcome data, the analysis population, multiplicity, or adherence to a detailed analysis plan.
General statistical explanation: evidence from a randomized comparison is interpreted by considering both the estimated difference and its uncertainty, alongside study quality and relevance. Here, the design and endpoint are described, but the primary numerical comparison needed for that assessment is not reported in the registry record. The record therefore supports a clear account of the research question and limitations, but not a conclusion about the treatment effect.
13. Why This Trial Matters Statistically
This study illustrates why a registered outcome definition is not the same as a reported result. The registry identifies a clinically relevant continuous measure, specifies its measurement method, and describes an adjusted comparison. But without the estimated changes and uncertainty, readers cannot evaluate the size, direction or precision of the primary finding.
Early termination for low recruitment also highlights the distinction between a study’s design and the information ultimately available. The study enrolled 39 participants, while its planned enrollment target and original sample-size justification are not reported in the registry record. The stated sample-size calculations are planning illustrations based on an observed effect, not observed power. Statistical planning assumptions cannot replace a completed outcome report.
The statistical method is described at a high level, including baseline adjustment, but key interpretive details are absent. The registry does not report missing-data procedures, analysis populations, multiplicity handling or a detailed analysis plan. These omissions matter because they affect how readers judge reliability and reproducibility, particularly when a study ends early.
For clinical researchers and biostatisticians, the record demonstrates the value of complete results reporting: an endpoint definition and an analysis method are most useful when accompanied by estimates and measures of uncertainty. It also shows the importance of distinguishing descriptive safety counts from a fully interpretable safety comparison. The available information is enough to reconstruct the broad question and design, but not the primary statistical result.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most consequential limitation is that numerical results for the primary outcome are not reported in the registry record. The registered endpoint and statistical model are described, but the estimated changes, adjusted between-group comparison and uncertainty are absent. This prevents assessment of effect size and precision.
The study was terminated early because of low recruitment and enrolled 39 participants. The registry does not report the intended enrollment target or the original sample-size justification. It also does not explain the recruitment difficulty beyond identifying it as the reason for early termination. Consequently, the implications of early termination for the intended analysis cannot be quantified from the record.
The registry does not report the analysis population, number of participants with week-12 measurements, missing-data handling, adherence, or sensitivity analyses. It also does not give eligibility criteria in detail or report background therapies, despite describing the study as an add-on study. The roles covered by triple masking, the randomization procedures and the detailed analysis plan are not reported in the registry record.
Safety information is limited to group counts and a list of serious-event terms with percentages. Deaths are not reported in the registry record, and further details about event timing, attribution and ascertainment are not available. The record also does not describe multiplicity procedures or interim analyses. These limitations are gaps in what the registry reports; they should not be treated as proof that the relevant procedures or information did not exist outside the registry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy of Aliskiren in the Treatment of Diabetic Macular Edema — NCT00768040.
- Registry record last updated 2012-03-06; status last verified 2012-02.
- Results first posted 2012-03-06.
- 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
NCT00768040 is a randomized, parallel-group, phase 2 study of oral aliskiren for diabetic macular edema. The registry describes triple masking and a placebo-controlled add-on design. Aliskiren 300 mg once daily and matching placebo were each described for 12 weeks. The study enrolled 39 participants and was terminated early because of low recruitment. The registry records a start date of 2008-09 and primary completion of 2011-02.
The primary outcome was change from baseline to week 12 in central retinal thickness, measured by optical coherence tomography and analyzed using ANCOVA with baseline as a covariate and treatment as a fixed factor. Numerical primary outcome results are not reported in the registry record. Safety entries list serious adverse events affecting 2 of 20 participants at risk in the aliskiren group and 2 of 19 in the placebo group; other adverse-event counts are also listed. Deaths and detailed analysis procedures are not reported in the registry record.