ACE-Inhibitor Effects on Total Hip and Knee Arthroplasty Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ACE-Inhibitor Effects on Total Hip and Knee Arthroplasty Patients (NCT01867047), a randomized na study. The primary outcome is Number of Participants With Mild Hypotension.

2. Clinical Question

The clinical question concerns the timing of ACE-I use around surgery and a threshold-defined blood-pressure outcome during the hospital period. The treatment strategies are distinct: one continues medication through the day of surgery, while the other stops it before surgery. The registry record identifies both strategies as drug interventions and describes randomized allocation, but does not report the details of the randomization procedure.

The primary outcome is specified as a count of participants with mild hypotension, rather than a continuous measure of blood pressure or a measure of how long hypotension lasted. The stated threshold is SBP less than 85 mmHG. The registry also lists transfer to an intensive care unit, receipt of allogeneic blood, and acute kidney injury as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. The record does not report a single primary-outcome comparison that would establish how the groups differed on the stated question.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. Participants were assigned to an ACE-I Continuation Group or an ACE-I Cessation Group. The continuation strategy was to take ACE-I through the day of surgery. The cessation strategy was to stop two days before surgery, with the last dose more than 48 hours before surgery. The record does not report whether participants, clinicians, or outcome assessors were blinded beyond identifying the study as having no masking.

The study concerns elective total hip or knee arthroplasty. The listed conditions are adverse effects of ACE inhibitors and hypotension. The sponsor is Duke University. The phase is recorded as NA. The registry lists enrollment as 59, a start date of 2013-06, primary completion on 2016-06-24, and status as terminated. The reason for termination and the number of participants who completed follow-up are not reported in the registry record.

The primary outcome timeframe runs from baseline to discharge from hospital, approximately 5 days. The outcome is the number of participants with mild hypotension under the stated SBP threshold. The registry lists 7 outcome measures and 5 analyses, but does not describe the full analysis plan or identify which analyses correspond to each outcome. The number enrolled should not be treated as the number included in every outcome analysis: the adverse-event summary separately lists 23 participants at risk in each group. The registry record does not explain the relationship between those figures or report analysis-population definitions.

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: Randomization of participants occurred only if the proposed inclusion/exclusion criteria were met.

Overall Study

Reasons for not completing this period:

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.

Population: Participants who completed the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Mild Hypotension, measured over From baseline to discharge from hospital (approximately 5 days).

The primary endpoint counts participants with mild hypotension, defined in the registry as systolic blood pressure (SBP) less than 85 mmHG. Its stated timeframe is from baseline to discharge from hospital, approximately 5 days. It is therefore a threshold-based participant outcome: a participant is counted if the specified blood-pressure criterion is met during the period described. The registry does not specify in the available outcome description how many measurements were taken, how repeated readings were handled, or whether the threshold had to be met once or on multiple occasions.

In general, a binary endpoint reduces an outcome to whether an event was recorded or not recorded for each participant. This can make the result interpretable as a count of participants meeting a predefined criterion, but it does not retain details such as the exact blood-pressure values, duration, or recurrence of episodes. Those features cannot be inferred from the endpoint definition. The registry labels the outcome as a count of participants, not as a continuous blood-pressure change.

A threshold-based outcome can be used to assess whether a defined event occurred during a clinically relevant observation period. The record does not state why this particular threshold was selected or provide a separate justification for using mild hypotension as the primary outcome. No primary-outcome event counts, group comparison, or uncertainty estimate are reported in the registry record, so the endpoint definition alone does not show how often the event occurred or whether the groups differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes randomized allocation to two parallel groups. Randomization is intended, in general, to make assignment independent of participants’ measured and unmeasured characteristics, reducing systematic differences between groups at baseline. It does not guarantee identical groups, especially in a limited-sized study, and it does not replace reporting baseline characteristics or the analysis used. The registry record does not describe the sequence-generation method, allocation concealment, or any stratification factors.

What does the primary endpoint count?

The primary endpoint is a binary participant outcome summarized as a count: whether a participant experienced mild hypotension under the stated definition of SBP less than 85 mmHG during the period from baseline to discharge, approximately 5 days. For this type of endpoint, a group’s event count is usually interpreted alongside the number of participants assessed. A comparative analysis can express how event occurrence differs between groups, but the record does not report the primary event counts or a primary comparison. No relative or absolute effect should be inferred from the definition alone.

In general, a confidence interval describes a range of effect values compatible with the data and the specified statistical method. Its width reflects the precision of the estimate; it is not a guarantee that the true effect lies in that range. A p-value, in general, measures how unusual data at least as discrepant as those observed would be under a stated null model. It is not the probability that the null hypothesis is true, and it does not describe clinical importance. The registry record does not report a primary effect estimate, confidence interval, or p-value, so these concepts cannot be applied to a primary result for this trial.

What do the planning assumptions mean?

The recorded planning illustration assumptions specify a two-sided significance level of 0.05, equal allocation, and a normal approximation. They describe an illustrative calculation based on a stated fraction of the observed effect, rather than the trial’s own design justification. For outcomes other than time-to-event outcomes, the planning convention is participants per arm; for time-to-event outcomes, the convention is a total event count. These are planning concepts, not observed trial outcomes. A planning sample size is not observed power, and it does not show that a trial with its actual enrollment had a particular probability of detecting an effect.

In general, planning calculations depend on the assumed effect, variability or event frequency, allocation, significance level, and target power. If the assumed effect changes, the resulting planned sample size can change. A calculation based on an observed effect is especially dependent on that estimate and should not be mistaken for a prospective justification. The registry record does not report the original sample-size justification, target power, or the numerical planning estimates in its study description.

Why can over-dispersion matter?

Over-dispersion is a general concern when variation in observed counts is greater than a statistical model expects. If a model assumes more uniformity than the data support, uncertainty estimates can be too small and tests can appear more decisive than warranted. For a binary participant outcome, the exact analysis depends on the design and the data structure; a count alone does not determine which method is appropriate. The registry record does not report an over-dispersion assessment or describe a model for the primary outcome. No claim about over-dispersion or model fit can therefore be made for this trial.

The record identifies the study as having no masking. In general, lack of masking can matter when care decisions, measurement, or classification of outcomes could be influenced by knowledge of group assignment. The primary endpoint is described using an SBP threshold, but the registry does not state how measurements were collected or whether outcome assessors were independent of treatment decisions. The possibility of measurement or performance effects cannot be quantified from the record.

The outcome description also leaves operational details unspecified. The registry does not report how missing blood-pressure observations were handled, what constituted a complete assessment, whether the analysis followed randomized assignment, or whether any adjusted model was used. Those details matter because they determine which observations contribute to the estimate and how uncertainty is calculated. The reported design and endpoint definition alone are not enough to reconstruct an analysis or reproduce a comparative result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and 5 analyses. It also identifies several secondary outcomes, including transfer to an intensive care unit, receipt of allogeneic blood, and acute kidney injury. Having multiple outcomes or analyses raises a general multiplicity issue: when several statistical tests are performed, the chance of obtaining at least one apparently unusual result can increase if each test is interpreted separately. Whether a correction is appropriate depends on the prespecified questions and analysis plan. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which outcome comparisons were designated as confirmatory.

The record does not present a single primary-outcome comparison, noting that the outcome has several categories or time points and was not reduced to one comparison. It does not specify how those categories or time points were to be combined, prioritized, or analyzed. Without that information, it is not possible to identify a unique primary test or assess how it relates to the listed analyses.

Missing-data methods are not reported in the registry record. The record does not state whether outcome observations were missing, how missing measurements were handled, or whether any sensitivity analyses were conducted. It also does not define the analysis populations or say whether participants were analyzed according to randomized assignment. The enrollment figure and the adverse-event denominators do not resolve those questions. Accordingly, the extent to which missing data or analysis-population choices could affect an estimate cannot be assessed from the registry record.

11. 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 adverse-event summary lists 23 participants at risk in the Continuation Group and 23 in the Cessation Group. In each group, the number with a serious adverse event is 0, the number with another adverse event is 0, and deaths are 0. These are the counts reported for the groups in that summary. They are distinct from the primary endpoint of mild hypotension and do not provide the primary-outcome results.

A zero count in a recorded summary means that no affected participants are listed for that category among the participants at risk in that summary. In general, zero observed events does not establish that an event is impossible or that there is no safety risk. The precision of a safety estimate depends on the number observed, the number assessed, and the completeness and duration of follow-up. The registry record does not provide additional detail about safety-event definitions, collection procedures, or follow-up beyond the reported primary outcome timeframe.

The enrollment figure is 59, while the adverse-event summary lists 23 at risk in each group. The record does not explain the relationship between these figures, so the adverse-event denominators should be read as specific to that summary rather than as a complete account of trial participation. These counts do not support broader conclusions about safety outside the listed participants, event categories, and recorded follow-up.

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

The registry record describes a randomized comparison of two perioperative medication strategies in people undergoing elective total hip or knee arthroplasty. One strategy continued ACE-I through the day of surgery; the other stopped it before surgery, with the last dose more than 48 hours before surgery. The primary endpoint was the number of participants meeting a threshold definition of mild hypotension from baseline to hospital discharge, approximately 5 days.

That description clarifies the question the study set out to address, but the registry record does not report a single primary-outcome comparison or its underlying group counts. It therefore does not show the direction or size of a difference in mild hypotension, nor how precise any difference may be. The secondary outcomes are named, but their numerical results are not reported in the registry record. The adverse-event summary reports zero serious events, zero other adverse events, and zero deaths in each group among 23 participants at risk per group; these figures do not substitute for results on the primary or secondary outcomes.

The status is terminated, and the reason is not reported in the registry record. Neither that status nor the enrollment figure of 59 establishes why the study stopped, how many participants completed each assessment, or whether the available outcome data represent all participants enrolled. The record does not report the analysis populations, missing-data approach, or a complete statistical analysis plan.

In general, results from a clinical trial are best understood through the outcome definition, group-specific data, effect estimate, and uncertainty. Here, the outcome definition and broad design are available, but the primary comparative result is not. The available registry information therefore supports a description of the trial question and its reported safety counts, not a conclusion about the effect of either strategy on hypotension or other clinical outcomes.

13. Why This Trial Matters Statistically

This trial is statistically notable because the registry describes a randomized comparison while not reporting a single primary-outcome comparison. Randomization clarifies the intended comparison, but the absence of group-specific primary event counts and an effect estimate prevents readers from assessing the magnitude, direction, or precision of the outcome contrast. The result is a useful distinction between knowing what a trial set out to measure and knowing what its posted data show.

The endpoint is a threshold-based count over a defined hospital period. Such an outcome compresses potentially varied blood-pressure experiences into whether the threshold criterion was met. In general, that can aid interpretation of event occurrence, while leaving unanswered questions about measurement frequency, duration, severity beyond the threshold, and repeat episodes. The registry outcome description does not resolve those operational details.

The record also illustrates why enrollment and analysis denominators should not be treated as interchangeable. Enrollment is listed as 59, while the adverse-event summary uses 23 participants at risk in each group. Without an explanation of the relationship between those counts, they answer different reporting questions and cannot establish the primary-outcome analysis population.

Finally, the status is terminated, but the reason is not reported in the registry record. The status alone cannot explain the evidence available or the absence of a primary comparison. For statistical interpretation, transparent reporting of outcomes, denominators, missing-data handling, and analysis methods is essential. Those details are not reported sufficiently to evaluate a comparative effect.

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 central limitation for interpreting this trial is that the registry record does not provide a primary-outcome comparison. It identifies the event definition and timeframe, but does not report primary event counts by group, an effect estimate, or its uncertainty. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. The resulting information does not establish the observed pattern of mild hypotension between the groups.

The record lists enrollment as 59 but does not explain how many participants contributed to each outcome analysis. The adverse-event summary lists 23 participants at risk per group, with no explanation of how those denominators relate to enrollment. The reason for trial termination is not reported. Participant characteristics, eligibility details, and the number completing the study are also not reported in the registry record.

Important analysis details are absent, including the randomization procedure, analysis populations, missing-data handling, and whether any adjusted analyses were conducted. The registry identifies no masking, but does not describe outcome measurement procedures or the role of assessors. It lists 7 outcome measures and 5 analyses, yet does not report a testing hierarchy or multiplicity approach. These omissions limit evaluation of potential bias, analysis choices, and the precision of any result.

Numerical results for the listed secondary outcomes are not reported in the registry record. The adverse-event summary contains zero counts in the reported categories, but its denominators and scope do not answer the primary clinical question or establish safety beyond the recorded summary. The registry also does not report the original sample-size justification or the reason for stopping the trial. These limitations leave the trial’s comparative outcome findings unresolved in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ACE-Inhibitor Effects on Total Hip and Knee Arthroplasty Patients — NCT01867047.
• Registry record last updated 2017-09-28; status last verified 2017-06.
• Results first posted 2017-09-28.
• 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

The registry describes NCT01867047, a randomized, parallel-group study with no masking, sponsored by Duke University. It compares continuing ACE-I through the day of surgery with stopping ACE-I two days before surgery, with the last dose more than 48 hours before surgery, among participants undergoing elective total hip or knee arthroplasty. Enrollment is listed as 59; status is terminated. The study start is recorded as 2013-06 and primary completion as 2016-06-24.

The primary outcome is the number of participants with mild hypotension, defined as SBP less than 85 mmHG from baseline to discharge, approximately 5 days. The registry does not report a single primary-outcome comparison. It lists 7 outcome measures and 5 analyses, and names secondary outcomes of ICU transfer, allogeneic blood receipt, and acute kidney injury. The adverse-event summary lists 23 participants at risk in each group and zero serious events, other adverse events, and deaths in each group. The reason for termination and the primary outcome results are not reported in the registry record.