Benazepril Hydrochloride, Lisinopril, Ramipril, or Losartan Potassium in Treating Hypertension in Patients With Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Benazepril Hydrochloride, Lisinopril, Ramipril, or Losartan Potassium in Treating Hypertension in Patients With Solid Tumors (NCT01234922), a randomized phase 2 study. The primary outcome is Changes in Ang1-7 Levels Among Patients After ACE-I/ARB Treatment Measured in Picogram/Milliliter.

2. Clinical Question

The study’s stated rationale concerns blood-pressure treatment and pro-angiogenic hormones in patients with cancer and hypertension. A secondary outcome names changes in Ang II, VEGF, PlGF, and ACE levels. Those objectives provide context for measuring a biological marker, but the registry record does not establish what change in Ang1-7 would mean for an individual patient or for clinical outcomes. The outcome should therefore be read as a short-term laboratory measure, not as a direct measure of blood-pressure control, tumor response, or patient benefit.

3. Trial Design

This was a phase II, randomized, parallel-arm trial with no masking. The registry record lists enrollment of 6 and a terminated status. It lists a study start of 2011-02 and primary completion of 2013-12. The reason for termination and the timing of the termination are not reported in the registry record.

Participants were assigned among four treatment arms. Arm I received oral benazepril hydrochloride once daily on days 1-7. Arm II received oral lisinopril once daily on days 1-7. Arm III received oral ramipril twice daily on days 1-7. Arm IV received oral losartan potassium once daily on days 1-7. Laboratory biomarker analysis is also listed as an intervention, but details of the laboratory procedures are not reported in the registry record.

Randomization is intended to reduce systematic differences between treatment groups at the point of assignment. In a parallel-arm design, participants receive an assigned treatment rather than crossing through all treatments. With enrollment of 6 across four arms, however, the posted arm sizes are only 1, 1, 2, and 2. Such small groups offer little information about the range of participant characteristics or the variability of outcomes within each treatment group. Randomization does not remove this limitation, and the registry record does not report a baseline comparison or adjusted analysis.

The record does not describe the allocation sequence, concealment procedures, adherence, concurrent treatments, or the reason the trial was terminated. It also does not report a protocol-based sample-size justification or a prespecified statistical analysis plan. These omissions prevent assessment of how planned methods and trial conduct align with the posted outcome summaries.

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 Changes in Ang1-7 Levels Among Patients After ACE-I/ARB Treatment Measured in Picogram/Milliliter, measured over 7 days post-baseline.

The primary endpoint is described as changes in Ang1-7 levels among patients after ACE-I/ARB treatment, measured in picogram/milliliter. The stated timeframe is 7 days post-baseline. Ang1-7 is a laboratory biomarker, so this endpoint records a biological measurement rather than a direct clinical outcome such as symptoms, blood pressure, tumor response, or survival. The registry record does not further define the measurement procedure or explain how the change was calculated.

Biomarkers can be used to study biological responses over a specified period. In this trial, measuring Ang1-7 after a short treatment period fits the stated interest in pro-angiogenic hormones among cancer patients with hypertension. A biomarker result may help describe a biological pattern, but its interpretation depends on the measurement’s reliability, the clinical meaning of different values, and the strength of the comparison. Those details are not reported in the registry record.

The posted endpoint summaries are means and standard deviations for each arm. The mean describes the central value in the reported group, while the standard deviation describes dispersion around that mean. The summaries do not provide individual measurements or an estimate of the difference between treatments. Because the registry record does not report a two-arm comparison, the endpoint summaries are descriptive and cannot establish that the arms differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous: Ang1-7 is measured on a numerical scale in picogram/milliliter. The registry record summarizes each arm with a mean and standard deviation. The mean is the arithmetic average of the observations in a group; the standard deviation describes how spread out those observations are around their mean. These are descriptive statistics. By themselves, they do not test whether treatment groups differ or quantify the uncertainty in a contrast between them.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. It does not guarantee balance in any particular trial, especially when groups are extremely small. Here the arm sizes are 1, 1, 2, and 2, so chance differences in participant characteristics could substantially affect the observed means. The registry record does not report baseline characteristics that would allow readers to assess group balance, nor does it describe the randomization procedure in detail.

Why is the standard deviation limited in the smallest arms?

In general, a standard deviation estimates the spread of observations within a group. With one observation, there is no collection of within-group values from which to assess how much participants vary. The reported standard deviation of 0.0 in the two single-participant arms should therefore be read as a consequence of the available group summary, not evidence that the biomarker has no variation among people receiving those treatments. Even where two participants are represented, an estimate of spread from such a small group is highly uncertain. It cannot reliably describe the broader population’s variability.

Why is a comparison estimate important?

A treatment comparison is usually expressed as a contrast between groups, together with an indication of uncertainty. A confidence interval, in general, is a range of values compatible with the data under a specified statistical method and its assumptions. A narrow interval indicates greater precision than a wide interval; an interval that is wide signals that the estimate is uncertain. The registry record does not report a confidence interval or an inferential comparison for this endpoint. The descriptive means alone do not show the precision of a difference between treatments.

The record explicitly indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. No two-arm contrast should therefore be inferred from the arm summaries. The registry record also reports no analyses. It does not identify a statistical test, model, covariate adjustment, or method for handling the four treatment arms in a single analysis. Those choices cannot be reconstructed from the summaries.

What does over-dispersion mean in general?

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variability. For continuous outcomes, a model that assumes a particular residual spread may be poorly calibrated if the data are more variable than expected. This is a general statistical issue, not a finding established by these posted data. With so few observations, the registry summaries do not allow a reliable assessment of the shape or amount of outcome variability.

The sample-size planning assumptions described for the page are illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are hypothetical planning aids, not observed power and not evidence that the original trial was designed with those assumptions. The registry record does not report its own sample-size justification. Since a two-arm comparison for the continuous endpoint is not estimable in the posted results, an observed effect for that comparison is not available in the record to support an interpretation of a planning illustration.

In general, a sample-size calculation depends on the effect to be detected, outcome variability, significance level, desired power, allocation, and analysis method. Changing these assumptions can change the planning result. A planning calculation cannot repair sparse outcome data or establish that an observed treatment effect is real. It also cannot be interpreted as a probability that the trial’s findings are correct.

The appropriate statistical reading is consequently descriptive and cautious. The reported means and standard deviations preserve the posted numerical summaries, but the arm sizes and absence of a reported comparison leave treatment effects and their precision unresolved. No claim about statistical significance, equivalence, or a treatment ranking is supported by the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and one secondary outcome: change in Ang II, VEGF, PlGF, and ACE levels. The primary outcome is the Ang1-7 measure. It does not report how many separate statistical tests were planned for the secondary biomarkers, whether a hierarchy of outcomes was prespecified, or how multiplicity was to be handled. When many outcomes or comparisons are examined, the chance of a seemingly notable result arising by chance can increase. In general, multiplicity procedures can address that issue, but no such procedure is reported in the registry record.

The record reports no analyses. It does not report which participants were included in an analysis, whether the analysis followed assigned treatment, or how participants who did not complete the treatment period would be handled. The analysis population is not reported in the registry record. Although the overall enrollment is 6 and the outcome summaries list arm-specific sample sizes, the record does not explain whether these are all enrolled participants or whether any participants lacked a measurement.

Missing-data details are also not reported in the registry record. There is no description of missing measurements, reasons for missingness, imputation, or sensitivity analyses. In general, missing outcomes can affect interpretation when the availability of a measurement is related to participant characteristics or outcome values. With no account of missingness or analysis populations, readers cannot determine whether the posted summaries represent every enrolled participant or how missing measurements may have influenced them.

The protocol-based multiplicity plan, missing-data strategy, and analysis-population definitions are therefore unknown. These are not technical details that can be recovered from arm means alone; they are important parts of the analysis plan needed to interpret results as confirmatory evidence.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports zero serious adverse events among the participants at risk in each of the four arms: 1 in Arm I, 1 in Arm II, 2 in Arm III, and 2 in Arm IV. No serious adverse-event terms are listed. The death counts are not reported in the registry record.

For other adverse events, the record reports 1 affected participant among 1 at risk in Arm I, 1 among 1 in Arm II, 1 among 2 in Arm III, and 2 among 2 in Arm IV. These are small counts from a total enrollment of 6. They are descriptive reports, not precise estimates of how often events would occur in a larger population, and they do not support a reliable comparison of safety between medicines.

Serious and other adverse events are separate registry categories. A report of zero serious events does not mean that no adverse events occurred: the record lists other adverse events in every arm. Conversely, a count in the other-adverse-event category does not establish severity or causation. The registry record does not provide event descriptions for those other events, attribution to treatment, timing, or details about ascertainment. Safety interpretation is therefore limited to the posted counts and categories.

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

The posted result is a set of short-term, arm-level Ang1-7 summaries from a randomized phase II study. It gives the mean and standard deviation for each treatment arm at the stated seven-day post-baseline timeframe, alongside very small arm sizes. This is useful as a record of what was reported for the biomarker measurement, but it is not a reported estimate of the effect of one treatment compared with another.

The results do not show whether any treatment changed Ang1-7 from baseline, because the registry record does not describe the calculation of change or provide baseline measurements. The endpoint title refers to changes, while the posted summaries give a mean for each arm. Without a clear definition of the reported value and a baseline summary, the relationship between these arm means and within-participant change cannot be assessed from the registry record.

The results also do not establish whether the medicines affect blood pressure, cancer outcomes, or patient well-being. The primary measure is a biomarker, the treatment period is described as days 1-7, and no clinical endpoint comparison is reported. A biomarker pattern is not interchangeable with a demonstrated clinical effect. The registry record also does not report evidence that would connect the Ang1-7 measurements to clinical outcomes in this population.

Nor do the summaries establish equivalence between treatments. Failure to report a comparison is not evidence that treatments have the same effect, just as differences among descriptive means do not by themselves establish a real treatment difference. With the reported arm sizes, uncertainty is substantial, and no confidence intervals or inferential tests are available.

The most defensible reading is limited to description: several arm-specific biomarker summaries were posted for this small, terminated study. The summaries can motivate questions about measurement, analysis, and study conduct, but they do not settle those questions. No medical advice or treatment recommendation follows from these registry results.

13. Why This Trial Matters Statistically

This trial illustrates a distinction central to clinical biostatistics: an outcome summary is not the same as an estimate of a treatment effect. The registry record reports means and standard deviations, but does not report a two-arm comparison or an inferential analysis. Readers may notice that the arm means differ, yet the summaries alone do not quantify the uncertainty in those differences. Interpretation requires keeping descriptive values separate from comparative evidence.

The study also shows why sample size matters for both estimates and variability. The arm sizes are 1, 1, 2, and 2. In the single-participant arms, the reported standard deviation of 0.0 cannot characterize variation among participants. Even the groups with two participants provide little information about the population spread. In general, small samples can produce unstable averages and highly uncertain estimates, even when treatment allocation is randomized.

A further statistical issue is the distinction between a study’s design and a later planning illustration. The registry record does not report its own sample-size justification. A planning calculation based on an observed effect is not a substitute for a prespecified design rationale, nor is it evidence of observed power. That distinction matters especially when the posted results do not include an estimable treatment comparison.

Finally, outcome definitions and analysis details are essential. The endpoint is titled as a change, but the registry record does not explain how change was defined; it reports arm-level means at the stated timeframe. Missing-data handling, analysis populations, multiplicity methods, and the reason for termination are also not reported. These gaps show why complete registry reporting is part of statistical interpretability: readers need enough information to understand how the data connect to the question being asked.

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 main limitation is the very small enrollment of 6, distributed across four arms with sizes of 1, 1, 2, and 2. The posted summaries cannot precisely characterize outcome distributions or support stable estimates of treatment differences. The zero standard deviations in the one-participant arms do not represent evidence of uniform responses; those arms provide no meaningful estimate of between-participant spread.

The registry record does not report an inferential comparison for the primary continuous endpoint and identifies values as missing or not estimable for a two-arm comparison. It provides no confidence intervals, p-values, or adjusted estimates. The means should therefore not be interpreted as evidence that treatments differ or are equivalent.

There is also uncertainty about what the outcome summaries represent. The primary endpoint is titled as changes in Ang1-7, but the record does not explain how change was calculated or provide baseline values. The analysis population and missing-data methods are not reported, so the completeness of the outcome data cannot be assessed from the record.

The trial is marked terminated, but the reason and timing of termination are not reported in the registry record. The protocol-based sample-size justification and statistical analysis plan are not reported either. The record does not describe allocation concealment, adherence, laboratory procedures, or participant characteristics beyond the stated condition. These gaps limit assessment of potential bias and the applicability of the summaries.

Finally, the measurement is a short-term biomarker outcome, with a stated timeframe of 7 days post-baseline. The record does not establish how the biomarker relates to blood pressure, tumor outcomes, or other clinical endpoints. Safety reports are also limited to small event counts without descriptions of other adverse events or reported death counts. Each limitation constrains the scope of conclusions that can be drawn.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Benazepril Hydrochloride, Lisinopril, Ramipril, or Losartan Potassium in Treating Hypertension in Patients With Solid Tumors — NCT01234922.
• Registry record last updated 2018-08-28; status last verified 2018-07.
• Results first posted 2014-12-15.
• 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.

18. Record Summary

NCT01234922 is a terminated, randomized, unmasked, parallel phase II study sponsored by Wake Forest University Health Sciences. It enrolled 6 patients with hypertension and an unspecified adult solid tumor, protocol specific. The registry record lists a study start of 2011-02 and primary completion of 2013-12.

Four arms used benazepril hydrochloride, lisinopril, ramipril, or losartan potassium for days 1-7. The primary outcome concerns Ang1-7 levels at 7 days post-baseline. Arm-level means and standard deviations are reported, but no two-arm comparison or statistical analysis is reported. The reason for termination, analysis population, missing-data handling, and study-specific sample-size justification are not reported in the registry record.