Drug Use Investigation On Zithromac (Azithromycin) In HIV Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Drug Use Investigation On Zithromac (Azithromycin) In HIV Patients (NCT01227395), a registered phase not stated study. The primary outcome is Number of Participants With the Frequency of Treatment Related Adverse Events..

2. Clinical Question

The investigation was intended to examine the occurrence of adverse events during actual post-marketing use, verify therapeutic effects, detect unknown adverse drug reactions and drug interactions, and identify factors affecting safety and efficacy. Those aims are broader than the primary endpoint alone. The listed secondary outcomes concern the number of participants who responded to treatment and the number prevented by treatment, but their definitions and results are not reported in the registry record.

The central statistical question is descriptive: what treatment-related adverse-event count was recorded among the participants observed? A comparative question—whether that count differs from an appropriate control group—cannot be answered from the design described. The registry does not report a control group or a randomized assignment that would support a like-for-like comparison. It also does not report the primary outcome count or an analysis of that outcome. Consequently, the investigation’s stated goals should not be mistaken for reported evidence that quantifies therapeutic effects or estimates treatment-related risk.

3. Trial Design

The registry identifies this as a drug use investigation of Zithromac (azithromycin) in patients with HIV infection, with an official title describing Zithromac Tablets 600mg and a post-marketing commitment plan. Pfizer is listed as the sponsor. Enrollment is 476, and the study status is completed. The recorded start is 2002-07 and primary completion is 2012-03.

The intervention is azithromycin. The arm description says that patients in the azithromycin arm were taking azithromycin. The registry also reports adverse-event summaries under two use categories, Azithromycin for Prophylaxis and Azithromycin for Treatment. These categories describe different uses; they should not be read as randomized treatment groups or as a controlled comparison. Allocation is not stated, and the record explicitly does not characterize the arms as a like-for-like control comparison.

The registry’s brief summary describes an investigation of actual post-marketing use. Its stated objectives include assessing adverse events, verifying therapeutic effects, detecting unknown adverse drug reactions and drug interactions, and determining factors that may affect safety and efficacy. The primary outcome is the number of participants with treatment-related adverse events, with a timeframe of 9 years(MAX). The record lists 13 outcome measures and 9 analyses, but does not explain the analysis methods or which outcomes were included in those analyses.

The record does not describe recruitment procedures, eligibility details, participant follow-up, exposure duration, or the way participants were assigned to the prophylaxis and treatment categories. It also does not report a protocol-level sample-size justification. Any planning illustration based on observed effects is separate from the study’s own design and should not be treated as evidence of the original planning assumptions or as observed power.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No statistical analysis provided for the frequency of treatment related adverse events.

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 Number of Participants With the Frequency of Treatment Related Adverse Events., measured over 9 years(MAX).

The primary endpoint is titled “Number of Participants With the Frequency of Treatment Related Adverse Events.” Its unit is participants, and its parameter is a number. In practical terms, the endpoint is intended to count participants who experienced treatment-related adverse events during the stated timeframe of 9 years(MAX). The registry does not report the resulting count.

The endpoint distinguishes treatment-related events from adverse events generally. The registry defines adverse events as unfavorable events occurring after azithromycin administration regardless of whether they are causally related to azithromycin, including clinically problematic abnormal changes in laboratory test values. It says that treatment-related adverse events were evaluated in company with the causal relationship to azithromycin. The record does not describe how that relationship was assessed or what criteria were used to classify an event as treatment-related.

Counting participants with an event is a useful descriptive measure because it indicates how many people were affected, rather than how many event episodes occurred. It does not by itself show when events occurred, how long participants were exposed, how many events each participant had, or whether the observed count differs from a comparison group. General statistical context: a count of participants with an event can be interpreted alongside an appropriate denominator and information about follow-up, but the registry does not report the primary count or its statistical analysis. The serious-event summaries are not a substitute for the missing primary treatment-related endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports participant counts and describes a binary outcome type: participants with an event. It does not report statistical methods for the primary endpoint. The distinctions below explain how such outcomes are generally interpreted; they should not be read as methods confirmed for this investigation.

What does a participant count represent?

For an event outcome, a participant is generally classified according to whether at least one qualifying event occurred during the observation period. A count of affected participants is not the same as a count of all event episodes: a participant with multiple episodes may still contribute only once to a participant-level count. The registry’s primary outcome is expressed in participants, but it does not explain whether or how repeated events were handled in the analyses.

A count is most informative when read with the number of participants who could have experienced the event and with a clear description of the observation period. The registry reports denominators for the serious and other adverse-event summaries, but it does not report the primary endpoint count. The timeframe for that endpoint is stated as 9 years(MAX); the record does not explain how that maximum timeframe relates to each participant’s actual follow-up or exposure.

What can a comparison establish?

General statistical context: a controlled comparison can help distinguish differences associated with an intervention from differences related to participant characteristics, follow-up, or other factors. Random assignment, when used and properly carried out, supports comparability of groups on average. This registry does not report randomized allocation, and allocation is not stated. It also identifies no like-for-like control comparison. The prophylaxis and treatment categories represent different azithromycin uses, so their descriptive counts should not be treated as though the groups were exchangeable or as a direct estimate of a treatment effect.

Even when two groups have counts and denominators, a numerical contrast alone does not establish causation. Differences in the kinds of participants, reasons for use, observation time, or event recording could affect the observed summaries. The registry record does not report details that would allow those factors to be assessed or adjusted for.

Why are uncertainty estimates useful?

General statistical context: a confidence interval describes the range of values compatible with an estimate under a stated statistical model and procedure. It helps readers judge precision, rather than treating a single estimate as exact. A p-value, when used appropriately, addresses how compatible observed data are with a specified null model; it is not a measure of clinical importance and does not establish causality. Neither confidence intervals nor p-values for the primary treatment-related adverse-event outcome are reported in the registry record. No inferential method for that endpoint is described.

For event counts, precision depends in part on how many participants are observed and how frequently events occur, as well as the analytic assumptions. Sparse outcomes can yield imprecise estimates, especially for comparisons. General statistical context: methods for binary outcomes may estimate a probability or compare probabilities, but their interpretation depends on the design, outcome definition, follow-up, and handling of missing observations. The registry supplies no primary endpoint estimate to which such uncertainty could be attached.

How should the planning illustrations be understood?

The planning assumptions describe illustrations based on an observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm. These assumptions explain the basis of the planning illustrations, but the registry does not report a protocol sample-size justification. The illustrations do not show that the original investigation was designed with those assumptions, and they are not observed power or an outcome of the study.

General statistical context: a planning sample size is conditional on assumptions about the effect to detect, variability or event frequency, allocation, and the chosen error rate. It is not a direct measure of whether a completed study found an effect. A calculation based on an observed effect is particularly distinct from a prospective design justification because the observed effect is known only after data have been collected. No numeric planning result or observed primary effect is reported in the registry record.

What about multiple outcomes and analyses?

The registry lists 13 outcome measures and 9 analyses. When many outcomes or comparisons are examined, general statistical context is that the chance of at least one apparently unusual result can increase if each is interpreted independently. Multiplicity procedures can address this issue, but their choice depends on the analysis plan and inferential goals. The record does not report whether adjustments were used, which outcomes were analyzed, or how analyses related to the listed outcomes. It is therefore not possible to infer a multiplicity strategy from the counts alone.

The record also does not describe missing-data handling, analysis populations, or a statistical model for the primary endpoint. These omissions limit the ability to reproduce or evaluate any primary analysis. The appropriate conclusion is not that a particular method was or was not used in practice, but that these methodological details are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Azithromycin for Prophylaxis", "Azithromycin for Treatment")
n      <- c(391, 84)
events <- c(73, 10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Azithromycin for Prophylaxis  391  73  18.7  14.9  22.9  15.1  22.8  15.1  22.8
ARM  Azithromycin for Treatment  84  10  11.9  5.9  20.8  6.6  20.5  6.6  20.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 9 analyses. It does not specify which outcomes were included in those analyses, whether the analyses were prespecified, or whether multiple comparisons were adjusted. General statistical context: when many outcomes or comparisons are tested, interpreting each result without regard to multiplicity can make apparently notable findings more likely by chance. A correction or other prespecified strategy may be appropriate in some settings, but the record does not report whether one was used. The number of outcomes and analyses alone does not reveal the analysis plan.

Missing-data methods are not reported in the registry record. The record does not explain whether participants with incomplete follow-up were excluded, how missing outcome status was treated, or whether any sensitivity analyses were conducted. These details matter because the number of participants observed and the completeness of follow-up can affect event summaries and the interpretation of an estimate.

Analysis populations are also not described. The registry does not say which participants were included in the primary endpoint analysis, or how the listed prophylaxis and treatment categories were defined for analysis. No statistical analysis is provided for the frequency of treatment-related adverse events. As a result, there is no reported primary analysis population, analysis method, or inferential result to assess.

These are reporting gaps, not evidence that a specific adjustment, missing-data method, or population definition was omitted from the investigators’ work. They mean that those choices cannot be evaluated from the registry record.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: progressive multifocal leukoencephalopathy (1.2%), anaemia (1.2%), renal failure acute (1.2%), renal disorder (1.2%), hepatic function abnormal (0.8%).

The registry reports serious and other adverse-event counts for two azithromycin use categories. For Azithromycin for Prophylaxis, 11 participants with serious adverse events and 62 with other adverse events are listed among 391 at risk. For Azithromycin for Treatment, the corresponding counts are 4 and 6 among 84 at risk. These are counts of participants, not counts of event episodes.

The record also lists serious-event terms with percentages: Progressive multifocal leukoencephalopathy, Anaemia, Renal failure acute, and Renal disorder at 1.2% each; Hepatic function abnormal at 0.8%; and Idiopathic thrombocytopenic purpura at 0.3%. The denominator and method used to calculate those percentages are not reported in the registry record. The registry does not report deaths.

These summaries should not be confused with the primary endpoint, which concerns treatment-related adverse events and has no reported result or statistical analysis. The serious-event summaries do not establish that azithromycin caused the events: the registry’s general adverse-event definition includes events regardless of causal relationship. Nor do the two use categories provide a controlled comparison. Without information on follow-up, participant characteristics, and a comparative analysis, the counts do not support a direct risk comparison between categories.

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

The record’s main contribution is to describe the purpose and broad structure of a completed post-marketing investigation of azithromycin use in patients with HIV infection. It records enrollment of 476 and identifies safety, therapeutic effects, unknown adverse drug reactions, drug interactions, and factors affecting safety and efficacy as objectives. It also lists descriptive adverse-event summaries for prophylaxis and treatment use categories.

What the record does not establish is equally important. The primary endpoint is the number of participants with treatment-related adverse events, but its result is not reported, and no statistical analysis is provided for that endpoint. The registry does not report a controlled, like-for-like comparison or randomized allocation. The available counts therefore cannot be interpreted as a causal comparison of azithromycin with a control or as a definitive comparison between prophylaxis and treatment use.

The outcome names for response and prevention appear among the secondary outcomes, but numerical results and definitions are not reported in the registry record. The stated aims to verify therapeutic effects and identify safety factors are not equivalent to reported findings that answer those questions. No conclusion about the magnitude or precision of a therapeutic effect can be drawn from the information recorded.

General statistical context: descriptive counts document what was recorded in the observed groups, while estimates of differences and their uncertainty require an appropriate analysis and clear design assumptions. Neither should be inferred from a study’s objectives alone. The serious-event counts and listed percentages can be read as registry summaries, but their interpretation is limited by the absence of further denominator, follow-up, and analysis details.

Thus, the posted information supports an account of what the investigation set out to examine and some adverse-event counts, but not a complete statistical assessment of the primary outcome or efficacy questions. Missing results in the registry record should not be interpreted as proof for or against an effect.

14. Why This Trial Matters Statistically

This investigation illustrates a common statistical challenge in post-marketing research: a broad safety and efficacy objective does not automatically translate into a reported, interpretable estimate for each question. The registry describes an intended evaluation of adverse events, therapeutic effects, unknown reactions, interactions, and factors associated with safety and efficacy. Yet the primary treatment-related adverse-event result and its statistical analysis are not reported in the registry record.

The distinction between an adverse event and a treatment-related adverse event is important. The registry defines adverse events broadly as unfavorable events after administration regardless of causal relationship, while saying that treatment-related events were evaluated in relation to causality. Without the primary count, criteria for judging relatedness, and details of follow-up, readers cannot assess how the primary endpoint was operationalized or how precisely it was estimated.

The record also shows why use categories should not automatically be treated as comparison arms. Prophylaxis and treatment are different contexts of use, and allocation is not stated. A comparison between their event counts would not, by itself, isolate an effect of treatment. Design and analysis details are essential for judging whether groups are comparable and what a contrast would mean.

Finally, the record lists multiple outcomes and analyses without reporting a multiplicity strategy, missing-data approach, or analysis populations. These features matter for reproducibility and for weighing any reported findings. The absence of these details does not show that the investigators did not consider them; it means that readers cannot evaluate them from the registry record. Statistically, this is a useful example of why outcome definitions, denominators, follow-up, comparison structure, and analysis methods all need to accompany results.

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.

The primary endpoint is not accompanied by a numerical result or statistical analysis in the registry record. Although the endpoint is a participant count over a timeframe of 9 years(MAX), the record does not report event counts, uncertainty estimates, or how that timeframe relates to individual follow-up. This prevents assessment of the primary result’s magnitude and precision.

The registry does not describe a randomized comparison, and allocation is not stated. It explicitly notes that the arms are not a like-for-like control comparison. The prophylaxis and treatment summaries are therefore descriptive categories rather than a basis for an unqualified comparative conclusion. The record does not provide enough design detail to evaluate differences in participant characteristics, exposure, follow-up, or event ascertainment across those categories.

The adverse-event summaries do not clarify how events were classified, how causal relationship was determined for the primary outcome, or how repeated events were handled. The serious-event term percentages have no reported denominator definition. The registry also does not report deaths.

Other limitations in the available record include the absence of participant eligibility and characteristic details, follow-up information, analysis populations, missing-data methods, and the statistical methods for the primary outcome. Although 13 outcome measures and 9 analyses are listed, the record does not explain which outcomes were analyzed or whether multiplicity was addressed. A protocol-level sample-size justification is not reported. These are limitations of what can be evaluated from the registry record; they should not be treated as proof that corresponding procedures were absent from the investigation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Drug Use Investigation On Zithromac (Azithromycin) In HIV Patients — NCT01227395.
• Registry record last updated 2013-04-26; status last verified 2013-04.
• Results first posted 2013-04-16.
• 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

This completed post-marketing drug use investigation concerns azithromycin (Zithromac) in patients with HIV infection. Pfizer is listed as sponsor; enrollment is 476. The record gives a start of 2002-07 and primary completion of 2012-03.

The primary outcome is the number of participants with treatment-related adverse events over 9 years(MAX). No statistical analysis is provided for that outcome, and its numerical result is not reported in the registry record. Descriptive serious and other adverse-event counts are listed for azithromycin use in prophylaxis and treatment, but those categories are not a like-for-like control comparison.

The investigation’s stated aims include assessing adverse events, therapeutic effects, unknown adverse drug reactions, drug interactions, and factors affecting safety and efficacy. The record lists 13 outcome measures and 9 analyses, but does not report key details on analysis methods, missing data, multiplicity, or analysis populations.