Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI. (NCT00430040), a randomized phase 4 study. The primary outcome is Change in Brachial Artery Vascular Reactivity.

2. Clinical Question

The trial addresses an add-on treatment question: whether carvedilol controlled release, when added to lisinopril, is associated with a different vascular-reactivity measure than lisinopril alone in people with type 2 diabetes and hypertension. This is distinct from a comparison of carvedilol with no treatment, because lisinopril is the active comparator and is named as the background treatment in the registry summary.

The registry describes the rationale as possible added benefits to blood vessels through suppression of free radicals and inflammation. That rationale explains why vascular reactivity and oxidative stress were of interest; it does not establish that either process changed. The primary endpoint was the percent change in brachial artery vascular reactivity at 6 months. The record reports group means and standard errors, but it does not report an inferential comparison between groups. The clinical question therefore remains more specific than the descriptive numbers can answer: the posted results do not quantify the uncertainty around a treatment contrast or establish whether the observed group summaries are compatible with no difference.

3. Trial Design

This was a randomized, phase 4, parallel-group trial with no masking. The registry lists University at Buffalo as sponsor, 14 as enrollment, and a status of terminated. The recorded study start is 2007-02, and the primary completion date is 2013-05. The reason for termination is not reported in the registry record. The registry does not provide further details about how randomization was generated or implemented, or whether allocation was concealed.

The study compared a carvedilol group with a lisinopril group. The brief description presents carvedilol controlled release as an addition to lisinopril treatment, while the arm descriptions identify the groups simply as carvedilol and lisinopril. The registry does not specify further details about the treatment schedules, dose, adherence, or whether lisinopril was continued in the carvedilol group throughout follow-up. Those details are not reported in the registry record.

The primary outcome was change in brachial artery vascular reactivity, expressed as percent change from baseline and assessed at 6 months. The registry also identifies change in oxidative stress in mononuclear cells as a secondary outcome. It lists 2 outcome measures but 0 analyses. Thus, the record contains endpoint summaries but does not provide analysis results that test the primary comparison. It also does not state how participants were assigned to analysis populations, how missing endpoint measurements were handled, or whether any protocol-defined interim analyses took place.

Enrollment and endpoint reporting are not the same thing. The registry lists 14 enrolled participants, while the primary endpoint summaries report 5 in the carvedilol group and 6 in the lisinopril group. The registry does not explain the difference between the enrollment total and those endpoint group counts. It should not be assumed from these figures alone that the unreported participants withdrew, were excluded, or lacked a measurement for a particular reason.

The record identifies this as a phase 4 trial, but does not report a protocol, detailed statistical analysis plan, sample-size justification, or rationale for termination. Without those details, the design features that can be described are limited to the recorded randomization, masking, group model, enrollment, endpoints, and status.

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

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 Change in Brachial Artery Vascular Reactivity, measured over 6 months.

The primary endpoint is percent change from baseline in brachial artery vascular reactivity at 6 months. The registry defines the measure as the value at 6 months minus the value at baseline, divided by the baseline value, then multiplied by 100. It is reported in percentage-of-change units. This endpoint is a continuous measure: its possible values can vary across a scale rather than representing only categories such as event versus no event.

Brachial artery vascular reactivity is used in this trial as a measure of vascular response. In general, measuring change from a baseline value can describe how an endpoint differs from its starting level over follow-up. Expressing that change relative to baseline places the change on a percentage scale. That explanation is general; it does not establish the biological interpretation or clinical importance of a particular value in this trial.

The registry reports a mean for each group and labels the accompanying dispersion as standard error. The carvedilol group has a reported mean of 28.0 and standard error of 20.0, with 5 participants listed; the lisinopril group has a mean of 19.0 and standard error of 17.0, with 6 participants listed. These are group summaries, not a reported estimate of the difference between groups. The registry does not give a confidence interval for a treatment contrast, a p-value, or a stated threshold for a clinically meaningful change.

The endpoint is useful for describing the trial's stated vascular question, but interpreting a change measure depends on how it was measured and on the uncertainty in the comparison. Details of the measurement procedure and any clinically meaningful threshold are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the reported summaries mean. The primary endpoint is continuous, and the registry reports a mean and standard error for each treatment group. A mean describes the central value of the observations included in a group summary. A standard error describes the precision of that estimated mean under the analysis assumptions; it is not the standard deviation of individual observations and does not show the range of participant-level values. The listed means and standard errors are 28.0 and 20.0 for carvedilol, and 19.0 and 17.0 for lisinopril. The associated endpoint group sizes are 5 and 6.

Why a treatment contrast matters. In a randomized comparison, the main inferential question is generally about the difference between groups, not whether each group mean has a particular value in isolation. A between-group estimate would quantify the contrast on the endpoint scale. A confidence interval would show the precision of that contrast by expressing a range of values compatible with the data and the analysis assumptions. A p-value, when reported, addresses how surprising the data would be under a specified null hypothesis and model. Neither a confidence interval nor a p-value is reported for the primary comparison in this registry record. No contrast should be reconstructed from the group summaries in this explanation.

What the dispersion label does and does not tell us. Standard error is useful for understanding precision of a mean, but it is not a direct description of participant-to-participant variability. The registry does not report individual observations, standard deviations, or a distributional plot in its outcome text. General statistical practice distinguishes these quantities because the standard error depends on both variability and the amount of information contributing to a mean. With limited group counts, the uncertainty around summaries can be important, but the record does not supply the inferential analysis needed to quantify uncertainty for the treatment contrast.

Change from baseline. The endpoint is defined as the 6-month value minus the baseline value, divided by the baseline value, multiplied by 100. This is a relative change measure rather than a direct report of the endpoint's value at follow-up. In general, change scores can be affected by baseline values and by measurement variability at both time points. Those are general considerations; the registry does not report baseline group values, participant-level changes, or an analysis adjusting for baseline. The record also does not give details about measurement reliability or the measurement procedure.

Randomization and masking. The registry identifies the study as randomized and parallel-group, with no masking. Randomization is generally intended to support comparability of treatment groups at assignment, while masking can reduce some forms of knowledge-related influence on care, measurement, or reporting. These are general concepts, not claims about how well they were achieved in this trial. The registry does not report the sequence-generation method, allocation concealment, who knew treatment assignment, or whether endpoint assessment was masked. No masking is the recorded status; further implementation details are not reported in the registry record.

Sample-size illustrations. The planning assumptions described for sample-size illustrations use a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial's own design. Planning calculations answer a hypothetical question about how many participants per arm might be needed under chosen assumptions. They are not observed power, do not explain the enrollment of 14, and do not show that the original study was designed using those assumptions. The registry does not report its own sample-size justification.

Why over-dispersion can matter in general. Over-dispersion means that observed variability is greater than a statistical model expects. When relevant, failing to account for it can make uncertainty estimates too narrow and statistical evidence appear stronger than warranted. This is a general concept, not a reported feature of this trial. The registry does not describe an over-dispersion assessment or a model for the primary endpoint. Given the continuous endpoint and the summary format, no conclusion about over-dispersion can be drawn from the posted information.

Recalculation and sponsor analysis. A simple unadjusted recalculation can sometimes be made from posted summary statistics, but the registry flags the continuous two-arm comparison as having values missing or not estimable. Accordingly, no recalculated comparison is available. There is no reported sponsor analysis to take precedence over a recalculation in the record's listed analysis results. The absence of a recalculation should not be filled by deriving a contrast from the two reported means; the required inferential information and analysis context are not reported.

Multiplicity. The registry lists 2 outcome measures, including the primary vascular-reactivity endpoint and a secondary oxidative-stress endpoint, but reports 0 analyses. Multiple outcomes can raise a general concern about how many hypotheses are examined and whether inferential error is controlled across them. The registry does not report a multiplicity strategy, an outcome hierarchy beyond the primary and secondary labels, or results for the secondary endpoint. It is therefore not possible to assess multiplicity handling or selective reporting from this record.

Missingness and analysis populations. The difference between the enrollment total and the group counts for the primary endpoint makes the analysis population important to understand, but does not establish why the counts differ. The registry does not report missing-data methods, reasons for unavailable measurements, imputation procedures, or whether an intention-to-treat population was used. These omissions prevent assessment of how missing outcome information may have influenced the reported summaries. The group counts should be read as the counts attached to the posted endpoint summaries, not as a complete account of participant flow.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Carvedilol", "Lisinopril")
n   <- c(5, 6)
m   <- c(28, 19)
sp  <- c(20, 17)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Carvedilol  5  28.000  44.721  -27.529  83.529
CARM  Lisinopril  6  19.000  41.641  -24.700  62.700

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures: the primary measure of change in brachial artery vascular reactivity and a secondary measure of change in oxidative stress in mononuclear cells. It reports 0 analyses. No analysis result is posted for the secondary outcome, and the record does not describe a plan for handling multiple outcomes or multiple statistical tests. In general, multiplicity matters because examining multiple outcomes or hypotheses can increase the chance of a nominally unusual result. Whether an adjustment or other strategy is appropriate depends on the study's aims and analysis plan; that plan is not reported in the registry record.

Enrollment is listed as 14, while the primary outcome summaries list 5 participants for carvedilol and 6 for lisinopril. The record does not explain these counts or give a participant flow account. It does not state the analysis population, whether all randomized participants were included, how unavailable endpoint values were handled, or whether any values were imputed. The reasons for the difference between enrollment and endpoint group counts are not reported in the registry record.

Missing-data methods can affect both the estimate and its uncertainty, particularly when unavailable measurements are related to participant characteristics or outcomes. That is a general statistical concern, not a claim about what occurred in this study. Without reasons for missingness and the analysis approach, the impact cannot be assessed. The registry also does not report an interim-analysis plan, stopping rule, or detailed statistical analysis plan. No assumptions about these procedures can be made from the terminated status.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse event counts of 0 affected participants among 7 at risk in the carvedilol group and 0 among 7 at risk in the lisinopril group. It also reports 0 deaths in each group. For other adverse events, the record likewise lists 0 affected participants among 7 at risk in each group. These are the counts recorded in the registry; they should not be interpreted as proof that no event of any kind occurred beyond the categories and reporting represented in the record.

At-risk counts are the denominators attached to these safety summaries. They are not the same as the primary endpoint group counts, which are 5 and 6. The registry does not explain why the safety counts and endpoint counts differ. It also does not provide event-specific serious adverse event terms, because no top serious terms are listed. Details about event definitions, collection methods, follow-up completeness, or causal attribution are not reported in the registry record.

In general, zero recorded events in a small group does not establish that an event is impossible or that two treatments have identical safety profiles. A safety comparison requires consideration of the amount and duration of observation, event ascertainment, and uncertainty. Those details are not available. The figures describe the recorded counts only and do not support a broader safety conclusion.

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

The registry record shows that a randomized, parallel-group phase 4 study compared carvedilol with lisinopril in people with type 2 diabetes and hypertension, with vascular reactivity designated as the primary endpoint. It reports group means for percent change at 6 months, along with standard errors and endpoint group sizes. It also reports no serious adverse events, other adverse events, or deaths in the listed at-risk groups.

Those details do not establish whether adding carvedilol changed vascular reactivity relative to lisinopril alone. The record contains no reported between-group estimate, confidence interval, or p-value for the primary outcome. Group means alone cannot show how precise a treatment contrast is, and the standard errors shown for the group means are not a substitute for uncertainty around that contrast. The record also does not state a threshold for a clinically meaningful change.

The registry's rationale mentions oxidative stress and inflammation, but the secondary oxidative-stress outcome has no posted analysis result. The rationale is not a result. Likewise, the terminated status does not explain why the trial ended or what effect, if any, termination had on recruitment, follow-up, or interpretation. Such details are not reported in the registry record.

The findings should therefore be read as limited descriptive reporting rather than a definitive comparison. The endpoint summaries represent the group counts attached to those results, and the reasons they do not match the enrollment total are not stated. The record does not provide enough information to determine the robustness of the result to missing data, to evaluate a planned statistical approach, or to assess whether the study had adequate precision for its question. This interpretation is about what the registry reports; it is not medical advice and does not imply that either treatment should or should not be used.

14. Why This Trial Matters Statistically

This trial is statistically notable because the registry contains a randomized comparison and numeric group summaries, yet reports 0 analyses. That distinction is important: descriptive values can show what was entered for each group, but an inferential comparison is needed to quantify the treatment contrast and its uncertainty. Without that contrast, the primary clinical question is not resolved by the posted numbers.

The endpoint summaries also illustrate why denominators matter. Enrollment is 14, while the primary endpoint group counts are 5 and 6. The safety summaries use 7 at risk in each group. These counts refer to different parts of the registry record, and the record does not explain the relationships among them. Careful statistical reading avoids treating them as interchangeable or inventing a participant-flow explanation.

The trial also highlights the difference between a study's stated rationale and its measured results. The registry describes interest in oxidative stress and inflammation, but only change in oxidative stress in mononuclear cells is listed as a secondary outcome, and no secondary analysis is posted. A biologically motivated question does not replace reported outcome evidence.

Finally, the record is marked terminated but does not state why. A status label can alert readers to the study's course, but it cannot establish whether termination was related to recruitment, logistics, safety, or results. The statistical lesson is to separate known design and outcome information from details that the record does not report. Doing so keeps descriptive summaries, planning illustrations, safety counts, and inferential evidence from being conflated.

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 restrict interpretation of the registry record. First, the primary outcome is reported only through group means, standard errors, and endpoint group counts. A between-group estimate and its confidence interval are not reported, nor is a p-value. The posted summaries therefore do not quantify the precision of the primary comparison.

Second, the primary endpoint counts are 5 for carvedilol and 6 for lisinopril, whereas enrollment is 14. The registry does not report participant flow, reasons for the count differences, or an analysis population definition. The possible influence of missing outcome data cannot be assessed because missing-data procedures and reasons for unavailable measurements are not reported.

Third, the registry does not report the randomization method, allocation concealment, measurement procedures, or detailed treatment schedules. It records no masking but does not state who knew assignments or whether endpoint assessment was masked. These details would help readers assess implementation and potential sources of bias.

Fourth, the record lists a secondary oxidative-stress outcome but no analysis results. It does not report a multiplicity strategy, detailed statistical analysis plan, or sample-size justification. The stated planning assumptions for illustrations are not evidence of the trial's own design assumptions. Finally, the study is marked terminated, but the reason and any implications for follow-up or analysis are not reported in the registry record. These limitations are specific gaps in the posted account; they do not establish what occurred in the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI. — NCT00430040.
• Registry record last updated 2024-04-16; status last verified 2024-03.
• Results first posted 2024-04-16.
• 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.

19. Record Summary

NCT00430040 is a randomized, unmasked, parallel-group phase 4 trial sponsored by University at Buffalo. The registry lists 14 enrolled participants and a terminated status. The recorded start is 2007-02, and primary completion is 2013-05. The reason for termination is not reported in the registry record.

The primary outcome is percent change from baseline in brachial artery vascular reactivity at 6 months. The registry reports a mean of 28.0 with standard error 20.0 for 5 participants in the carvedilol group, and a mean of 19.0 with standard error 17.0 for 6 participants in the lisinopril group. It lists change in oxidative stress in mononuclear cells as a secondary outcome. The record reports 0 analyses and no inferential comparison for the primary endpoint.

Safety summaries list 0 serious adverse events, 0 other adverse events, and 0 deaths in each group, with 7 at risk per group for the adverse-event counts. Further details about analysis populations, missing data, sample-size justification, and the termination reason are not reported in the registry record.