Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL) (NCT05156437), a randomized phase 4 study. The primary outcome is All-cause Mortality at Six (6) Months Post-surgery..

2. Clinical Question

In clinical-trial terms, the intended comparison concerned two postoperative antibiotic strategies: an oral course after the initial inpatient IV course, versus continuing IV therapy after that initial course. The registry record identifies the study as randomized and parallel-group, but does not report how participants were assigned between groups or the number assigned to each group. Its brief summary describes safety and compliance as aims, while the named primary endpoint is mortality. The listed secondary outcomes include readmission for recurrent infection or cardiac re-operation at six months and at one year, and cost of care. The record does not provide results for those outcomes.

3. Trial Design

The record describes OPTIMAL as a randomized, parallel-group, phase 4 study sponsored by West Virginia University. It lists enrollment of 5 and identifies the condition as endocarditis. Participants were assigned to Group I, the experimental group, or Group II, the control group. The study was unmasked: masking is listed as none. The registry record does not report the allocation procedure, whether assignment was concealed, or the number of participants assigned to either group.

The planned regimens shared an initial period of two weeks of postoperative inpatient IV antibiotic therapy. Group I then received four weeks of oral therapy with outpatient follow-up. Group II continued IV antibiotic therapy for four weeks, either as an inpatient or under facility supervision if an indwelling catheter was used. The listed drug names are examples recorded for the respective intervention groups; the record does not report which drug each participant received or how clinicians selected among the listed drugs.

The study start date is 2022-03-16, and the primary completion date is 2024-10-31. The current status is terminated. A termination date and reason are not reported in the registry record. The record also does not report details about recruitment, protocol amendments, adherence, or follow-up procedures beyond the descriptions of the treatment groups and outcome time points.

Randomization is intended, in general, to make treatment groups comparable with respect to measured and unmeasured baseline characteristics on average. It does not guarantee balance in a particular study, especially when enrollment is limited. Lack of masking can also matter: knowledge of an assigned strategy may affect care decisions, follow-up, or outcome assessment. These are general design considerations, not findings about how the trial was conducted. The record does not report enough detail to assess those processes.

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: Five participants were enrolled and assigned to two study arms (Group I: 4; Group II: 1). After surgery and treatment initiation, all were lost to follow-up before completing the six-week therapy period or reaching any follow-up visit, resulting in 0 completions. The only reason for non-completion was loss to follow-up; no participants withdrew consent, had adverse events, or were removed. All were classified as "Not Completed-Lost to Follow-up."

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants enrolled in the study were assigned to a study arm; however, all participants were lost to follow-up prior to the six-month assessment. As a result, no outcome data were collected for this measure in either arm, and no participants were included in the analysis population. No interim, partial, or alternative data were available for analysis.

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 All-cause Mortality at Six (6) Months Post-surgery., measured over Six months.

The primary endpoint was all-cause mortality at six months after surgery. It was defined as the incidence of death from any cause during the specified follow-up period. An all-cause endpoint does not require assigning a death to a particular cause, which can avoid uncertainty in cause-of-death classification. In general, mortality is a direct clinical outcome, but its interpretation depends on complete and sufficiently reliable outcome ascertainment.

For this trial, the endpoint was not observed in the analysis population. The registry record states that all enrolled participants were lost to follow-up before the six-month assessment. No outcome data were collected for either group, and no participants were included in the analysis population for the endpoint. Consequently, the record does not provide a mortality count, a comparison between groups, or an estimate of the treatment contrast. The endpoint remains the planned primary measure, but the registry record cannot establish what the mortality results would have been.

The brief summary describes safety and compliance as study aims, while the named primary endpoint is mortality. Those concepts are not interchangeable: mortality is one specific outcome, whereas safety and compliance can involve other measures and methods. The record does not report a distinct compliance endpoint or a complete account of safety outcomes. The named secondary outcomes concern readmission for recurrent infection or cardiac re-operation at six months and one year, and cost of care.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what can and cannot be learned from this record. The explanations below are general unless they explicitly describe a fact reported for OPTIMAL. The registry record identifies a randomized, parallel-group study, but does not report a statistical analysis plan. It lists zero analyses, and it does not provide an estimate or inferential result for the primary endpoint.

What does randomization contribute?

In general, randomization assigns participants to treatment strategies using a chance-based process. Its purpose is to reduce systematic differences between groups at the start of a study, including differences that investigators may not have measured. It does not guarantee that groups will be similar in every respect, and it does not prevent bias from missing outcomes, deviations from assigned care, or differences in how outcomes are measured. The record does not describe the allocation sequence or concealment, so those implementation details cannot be assessed.

A parallel-group design assigns participants to a strategy that is compared with the strategy assigned to another group. For OPTIMAL, the recorded strategies differed after the initial two weeks of postoperative inpatient IV therapy: one group was assigned oral therapy with outpatient follow-up, while the other continued IV therapy. The registry record does not report treatment adherence or crossover, so it is not possible to describe how closely participants followed their assignments.

What would an endpoint comparison estimate?

In general, a trial comparison needs an outcome measure for participants in each group, together with a defined analysis approach. For a binary endpoint such as whether death occurred by a specified assessment, an analysis might compare group event proportions or use another suitable model. The choice depends on the protocol, data structure, and assumptions. The registry record does not report an analysis method for mortality, and the endpoint data were not collected for either group. No trial-specific comparison can therefore be reconstructed from the reported information.

Uncertainty is usually communicated with a confidence interval, which describes a range of estimates compatible with the observed data under a statistical model and assumptions. A p-value, when used, measures how incompatible the observed data are with a specified null model; it is not the probability that a treatment works or that a conclusion is correct. Neither kind of inferential result is reported for this endpoint. More importantly, an inferential method cannot recover the missing mortality outcomes without assumptions that are not documented and data that are not present.

Why does complete loss to follow-up matter?

Missing outcome data reduce the information available for estimating a treatment effect. In general, the consequences depend on why outcomes are missing and how missingness relates to treatment assignment and the unobserved outcomes. If missingness is related to prognosis or treatment experience, an analysis limited to participants with observed outcomes can be biased. Statistical methods such as imputation or weighting may be considered in some studies, but they require data and assumptions, and they do not automatically remove bias.

For this primary endpoint, the record says all enrolled participants were lost before the six-month assessment and that no participants were included in the analysis population. It does not report reasons for loss, an imputation strategy, a sensitivity analysis, or an alternative mortality assessment. Without those details and without observed endpoint values, the extent or direction of any potential bias cannot be quantified. This is not simply a question of a wide confidence interval: the registry record reports no analyzed primary outcome data from which to estimate the group comparison.

What do the planning assumptions mean?

The record describes sample-size illustrations as planning calculations based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that time-to-event illustrations report total events using the Schoenfeld approach, while other illustrations report participants per arm. These are planning conventions, not observed trial findings and not evidence that a study had a particular probability of detecting an effect.

The record does not provide an observed effect for the primary endpoint, because no mortality outcome data were collected or analyzed. It also says the primary outcome was not reduced to one comparison because it has several categories or time points. Thus, the general planning description does not yield a trial-specific sample-size result for this endpoint. The registry record does not report the trial's own sample-size justification or design calculations. Any sample-size illustration must be kept separate from the study's enrollment and from observed outcomes; it cannot substitute for missing results.

What is the role of multiple-outcome planning?

When a study evaluates several outcomes or time points, general statistical practice considers how to define primary and secondary questions and how to interpret multiple tests. Testing many hypotheses can increase the chance of at least one apparently notable result by chance, depending on the testing strategy. Investigators may use a prespecified hierarchy, adjust significance thresholds, or emphasize estimation and uncertainty rather than a collection of isolated tests. The registry record does not report a multiplicity strategy or a statistical analysis plan. Since no analyses are listed, there are no reported tests to interpret or adjust.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 9 outcome measures, identifies all-cause mortality at six months as the primary endpoint, and names secondary outcomes involving readmission for recurrent infection or cardiac re-operation at six months and one year, plus cost of care. It does not report a statistical analysis plan, a hierarchy for secondary outcomes, or a method for addressing multiplicity. It also lists zero analyses. Therefore, there are no reported p-values or outcome estimates for which a multiplicity adjustment can be evaluated.

Multiplicity is a general concern when several outcomes, time points, or comparisons are examined. If many tests are conducted, the chance of at least one apparently unusual result can rise. A plan may control that issue by defining a primary question in advance, specifying a testing order, adjusting thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any such approach was planned. The existence of several listed outcome measures alone does not establish that multiple testing occurred.

Missing data are central to the primary result. The record states that all enrolled participants were lost to follow-up before the six-month assessment. No mortality outcome data were collected in either group, and no participants were included in the primary analysis population. Reasons for loss to follow-up, methods for recovering outcomes, imputation, sensitivity analyses, and assumptions about missingness are not reported in the registry record.

The record confirms that participants were assigned to a study arm, but it does not report the number assigned to each arm or define analysis populations beyond the statement that no participants entered the primary endpoint analysis. It is not possible to assess an intention-to-treat analysis, a per-protocol analysis, or another population-based approach from the posted information. General methods for missing-data analysis require assumptions; they cannot create observed mortality outcomes or establish what happened to participants whose status was not assessed.

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

The registry record documents a planned randomized comparison of postoperative antibiotic strategies and reports that the trial was terminated. It also reports enrollment of 5 and describes the primary endpoint as all-cause mortality at six months after surgery. These registry entries describe the study's design and status, not its comparative clinical outcome.

For the primary endpoint, the record reports that all participants were lost to follow-up before the six-month assessment. No outcome data were collected in either group, and no participants were included in the analysis population. As a result, the posted record does not show how many deaths occurred, provide a group-specific mortality estimate, or estimate a difference between the strategies. It also does not support a conclusion that the strategies were equivalent, that one was superior, or that either had a particular safety profile.

The brief summary describes safety and compliance as study aims. Those aims should not be read as findings. The registry record does not report results for the listed secondary outcomes of readmission for recurrent infection or cardiac re-operation at six months or one year, or cost of care. It lists zero analyses. The adverse-event entries show zero at risk, zero affected, and zero deaths for each group; these entries do not establish that no adverse events occurred, particularly when follow-up and outcome ascertainment are incomplete.

In general, absence of reported evidence is not evidence that two strategies have the same effect. A conclusion about a treatment comparison requires outcome data and an analysis capable of expressing both the estimate and its uncertainty. Here, the record supports a conclusion about the lack of a reported primary endpoint analysis, not about the direction or size of any treatment effect. The reason for trial termination and the reasons for loss to follow-up are not reported in the registry record, so explanations for the missing results would be speculative.

12. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a randomized design and an interpretable randomized comparison. Random assignment can support a causal comparison when outcomes are observed and analyzed, but it cannot replace follow-up. The registry record identifies a primary mortality endpoint and a six-month assessment, yet reports that all enrolled participants were lost before that assessment. As a result, there is no primary outcome estimate to interpret.

The record also illustrates why enrollment and analysis populations must be distinguished. It lists enrollment of 5 and states that no participants were included in the primary analysis population. The record does not report group-specific allocation counts. Enrollment alone does not establish how much information is available for a particular endpoint, especially when outcome ascertainment is incomplete.

Another statistical distinction is between a study's aims and its results. Safety and compliance appear in the brief summary, and several secondary outcomes are named, but the record lists zero analyses and gives no outcome estimates. A planned measure is not evidence that the measure was successfully collected or that a result was found. Similarly, planning illustrations based on an observed effect are not observed power and cannot supply missing outcome evidence.

The case also underscores the importance of reporting why data are missing, how missing outcomes were handled, and what analysis populations were defined. Those details are not reported in the registry record. Without them, readers cannot evaluate whether the missingness could have distorted a comparison or whether any sensitivity analysis was attempted. The statistical lesson is not a finding about which antibiotic strategy is preferable; it is that the available registry record does not support a comparative effect estimate.

13. 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 no primary endpoint data were collected. The registry record states that every enrolled participant was lost to follow-up before the six-month mortality assessment and that no participants entered the analysis population for this endpoint. This prevents estimation of mortality in either group and prevents a comparison of the assigned strategies. The cause, timing, and circumstances of loss to follow-up are not reported.

The record lists enrollment of 5, but does not provide the number assigned to each group. It does not report baseline characteristics, participant flow by group, adherence to the assigned regimens, crossover, or treatment received. These omissions limit assessment of how the randomized design was implemented and whether the planned regimens were delivered as described.

The registry record lists zero analyses and does not report results for the secondary outcomes or cost of care. It does not report a statistical analysis plan, sample-size justification, missing-data approach, sensitivity analyses, or multiplicity strategy. The listed sample-size assumptions describe planning illustrations, not the trial's own design rationale; the record does not provide a primary outcome effect on which to base an illustration.

The trial is listed as terminated, but the reason and date of termination are not reported in the registry record. The adverse-event entries list zero participants at risk, zero affected, and zero deaths in each group. In the context of incomplete follow-up, those entries should not be interpreted as proof that there were no adverse events. Taken together, the record permits description of the design and reporting gaps but not evaluation of comparative effectiveness or safety.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL) — NCT05156437.
• Registry record last updated 2026-05-05; status last verified 2026-04.
• Results first posted 2026-05-05.
• 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.

17. Record Summary

OPTIMAL is listed as a randomized, unmasked, parallel-group phase 4 study sponsored by West Virginia University, with enrollment of 5 and a status of terminated. The study began on 2022-03-16, and its primary completion date is 2024-10-31.

The comparison was between two postoperative antibiotic strategies for IVDA endocarditis after surgery. Both groups were assigned two weeks of inpatient IV therapy; Group I then received four weeks of oral therapy, while Group II continued IV therapy for four weeks. The primary endpoint was all-cause mortality at six months.

The registry record states that all enrolled participants were lost to follow-up before the six-month assessment. No primary outcome data were collected for either group, and no participants were included in the analysis population. The record lists zero analyses and does not report results for the named secondary outcomes. The reason for termination and the reasons for missing follow-up are not reported in the registry record.