Multicenter, Safety Study Of Maraviroc: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multicenter, Safety Study Of Maraviroc (NCT00478231), a non-randomized phase 3 study. The primary outcome is Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase 3, multicenter, open-label, non-comparative safety study of maraviroc. The registry classifies allocation as non-randomized and the model as single-group. With no randomized control group, the design describes safety experience during treatment but does not estimate a randomized between-group treatment effect. Open-label conduct means masking was absent; the record does not provide further information about how adverse events were assessed or classified.

The registry reports enrollment of 209 and identifies the safety analysis set as participants who received at least one dose of study medication. The safety counts list 206 participants at risk. The record does not explain the difference between enrolled participants and the safety group, so reasons for non-inclusion in the safety counts should not be inferred. The study began in 2007-07, had primary completion in 2010-08, and is listed as completed.

The primary endpoint covers Grade 3 and Grade 4 adverse events and serious adverse events from baseline to 30 days post-week 96 or early termination. The record also lists secondary outcomes concerning HIV-1 RNA, CD4 and CD8 counts and percentages, and CXCR4 tropism status. Although these outcomes are named, their numerical results are not reported in the registry record. The registry record does not report the treatment schedule, detailed eligibility criteria, reasons for early termination, or a statistical analysis plan.

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: A total of 638 participants were screened, out of which 429 participants were screen failures and 209 were assigned to the study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set composed of all participants who received at least one dose of study medication.

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 Grade 3 and Grade 4 Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Baseline to 30 days post-week 96 or early termination (ET).

The primary endpoint counts participants with Grade 3 and Grade 4 adverse events and serious adverse events during the period from baseline to 30 days post-week 96 or early termination. An adverse event is defined in the registry as an untoward medical occurrence or worsening of a pre-existing medical condition, whether or not related to study drug. Serious adverse events are defined by outcomes such as death, life-threatening events, persistent or significant disability, hospitalization, or congenital anomaly. Grade 3 events interrupt usual daily activity and traditionally require systemic drug therapy or other treatment; Grade 4 events are unacceptable and intolerable, irreversible, or cause imminent danger of death.

Counting participants with events is a way to describe how many people in the safety group experienced an event within the specified categories and follow-up period. Such counts can be useful for safety monitoring because they focus on people affected, rather than the total number of event episodes. In general, however, participant counts do not describe event duration, recurrence, or severity beyond the endpoint categories. The registry summary does not provide separate Grade 3 and Grade 4 counts, event-level details, or an attribution assessment that establishes whether events were caused by the study drug.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

The primary endpoint is framed as a number of participants with qualifying events. In general, a participant count gives the number of people meeting the outcome definition during the specified observation period. It is distinct from an event count: one participant could experience more than one event, while a participant-based endpoint generally counts that person as affected rather than counting every occurrence. The registry does not provide event-level data, so repeated events and the way they were handled cannot be assessed.

For this study, the posted summary identifies 206 participants at risk for the serious and other adverse event counts. It lists 34 participants for the serious adverse event category and 185 for the other adverse event category. Those counts should be understood within the registry's safety population definition. The record does not explain whether a participant could appear in both categories, nor does it provide separate Grade 3 and Grade 4 participant counts.

What does the follow-up period add?

The endpoint's observation window runs from baseline to 30 days post-week 96 or early termination. A defined window matters because the opportunity to observe an event depends on how long participants are followed. In general, participants who stop follow-up earlier may contribute less observation time than those followed through the planned endpoint. The registry does not report individual follow-up durations, exposure time, or reasons for early termination, so the posted counts cannot be adjusted for differences in time observed.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis method. A narrower interval indicates greater precision under that method, while a wider interval indicates more uncertainty. The registry record does not report confidence intervals for the adverse event counts or percentages. No interval should therefore be inferred from the counts alone. Statistical uncertainty is also only one consideration: a confidence interval cannot correct limitations arising from an absent comparison group, incomplete outcome reporting, or differences in participant follow-up.

Why does the design affect interpretation?

Random allocation can help balance participant characteristics between treatment groups, on average, and a concurrent control group can provide a reference for interpreting outcomes. This study was non-randomized, non-comparative, and single-group, so there is no concurrent control contrast in the registry record. In general, observed events in a single group cannot distinguish treatment effects from background illness, other exposures, or chance. The findings are therefore descriptive safety observations rather than a controlled estimate of causal effect.

The study was open-label, with no masking. In general, knowledge of treatment assignment can influence reporting or assessment, especially for outcomes requiring judgment. The registry does not describe assessment procedures or independent review, so the extent to which this could affect these event counts is not reported in the registry record. This limitation does not establish that assessments were biased; it identifies information needed to judge the possibility.

What do the planning calculations represent?

Any sample-size calculations associated with the posted results are planning illustrations, not a description of the study's original design and not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations concern hypothetical detection of a fraction of an observed effect, and non-time-to-event calculations are expressed as participants per arm for 80% power or another stated power level. These assumptions do not match the registry's single-group, non-comparative design and should not be mistaken for a randomized comparison conducted in this study. The registry record does not report its own sample-size justification or power calculation.

In general, over-dispersion occurs when variability in event counts exceeds what a simple statistical model assumes. Accounting for it can affect uncertainty estimates and tests. The registry does not report an over-dispersion assessment or a statistical model for the primary endpoint. Likewise, the posted record does not state whether estimates were adjusted for baseline characteristics, how missing outcomes were handled, or whether there were interim analyses. Those methods cannot be reconstructed from the event counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, including the primary safety endpoint and secondary measures of HIV-1 RNA, CD4 and CD8 counts and percentages, and CXCR4 tropism status. When many outcomes or repeated time points are assessed, the chance of at least one apparently notable result can increase if each is tested separately. In general, prespecified approaches to multiplicity can help control that risk, but the registry record does not report a multiplicity strategy or inferential analyses for these outcomes.

The secondary outcomes include assessments at multiple weeks and at early termination for several measures. The record names these outcomes but does not report numerical results, denominators at each assessment, or the number of participants with missing measurements. Missingness can matter because people with unavailable follow-up data may differ from those whose outcomes are observed. In general, complete-case summaries and methods that account for missing data answer different questions and rely on different assumptions. The registry record does not report a missing-data method or reasons for missingness.

The safety analysis set is defined as participants who received at least one dose of study medication. The event summary lists 206 at risk, while enrollment is 209. The registry does not explain the membership of the difference, report a flow of participants through follow-up, or state how participants who stopped treatment were handled in each analysis. It also does not report a detailed analysis plan or any analysis entries. These omissions limit evaluation of outcome completeness, analysis-population choices, and the consistency of reporting across the listed outcomes.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (1.9%), pyrexia (1.5%), pneumonia (1.5%), convulsion (1.5%), abdominal pain (1.0%).

The registry's safety summary gives a serious adverse event count of 34 participants and an other adverse event count of 185 participants, with 206 at risk in each category. These are participant counts, not counts of every event episode. The record does not explain whether people may be included in both categories, so the two counts should not be combined. It also does not give a separate count for Grade 3 events or Grade 4 events.

The serious adverse event terms listed include sepsis at 1.9%, pyrexia at 1.5%, pneumonia at 1.5%, convulsion at 1.5%, abdominal pain at 1.0%, and diarrhoea at 1.0%. The denominator and counting basis for these term percentages are not reported in the registry record. The terms are not, on their own, evidence that maraviroc caused the events; the registry's adverse event definition includes occurrences whether or not related to study drug.

The registry gives no death count in the safety summary, so deaths are not reported in the registry record. It also does not provide confidence intervals or a control group for comparison. These figures are therefore best read as descriptive safety reporting from the study group, with limited information about precision, attribution, and event overlap.

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

The result supports a description of adverse events recorded among participants in a single-group study of maraviroc. The registry lists 34 participants in the serious adverse event count and 185 in the other adverse event count, among 206 at risk for each. It also lists selected serious adverse event terms and their percentages. This information conveys the types and counts reported in the registry, within the study's definitions and follow-up period.

It does not establish that the drug caused any particular event, nor does it show what the event counts would have been under another treatment or without treatment. The study had no randomized comparator, and adverse events were defined irrespective of relation to study drug. A causal assessment would require more than observing that an event occurred during a study.

The figures also do not provide a complete account of the primary endpoint by severity. The endpoint title includes Grade 3 and Grade 4 adverse events and serious adverse events, but the posted summary does not separately report the Grade 3 and Grade 4 counts. The registry does not report confidence intervals, adjusted analyses, or a statistical test for the primary endpoint. The count data alone therefore do not quantify statistical precision or support an inferential comparison.

The record names additional virologic and immunologic outcomes but does not report their numerical results. It does not report details of missing data, individual follow-up, or the statistical plan. Those gaps matter when judging how comprehensively the observations represent the enrolled group and how outcome results were selected and analyzed.

In general, a safety study can document events occurring during exposure and contribute descriptive information. Its conclusions remain bounded by its design, outcome definitions, follow-up, and reporting. For this record, the most defensible reading is a set of descriptive adverse event counts and selected terms, not a conclusion about comparative safety or treatment effect.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between describing events and estimating a treatment effect. A single-group safety study can record adverse events over a defined period, but without a concurrent comparison group it cannot establish how those counts differ from what would occur under another treatment or no treatment. The design and the question being answered need to be considered together.

The registry's endpoint combines severity categories and serious adverse events in its title, while its posted summary reports serious and other adverse event counts. Separate Grade 3 and Grade 4 counts are not reported. This illustrates why endpoint definitions and result formats need to align: readers need enough detail to connect the reported counts to the prespecified outcome.

The record also distinguishes enrollment from the safety analysis set, which is defined by receipt of at least one dose. That distinction is important because a stated analysis population determines who contributes to a safety summary. The registry does not explain the participants not represented in the safety count, highlighting the value of participant flow and reasons for exclusion or discontinuation.

Finally, the record lists several secondary outcomes but does not report their numerical results or analysis entries. In general, transparent reporting of outcome results, uncertainty, missingness, and multiplicity methods helps readers assess the completeness and reliability of evidence. The available record offers a basis for describing safety reports, while leaving important questions about analysis and precision unanswered.

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 for interpretation is the absence of a control group. This non-randomized, single-group study cannot make a like-for-like comparison or isolate the effect of maraviroc from underlying illness, other exposures, and events that would occur in the absence of treatment. The open-label design also means masking was absent; assessment procedures are not reported in the registry record.

Outcome reporting is incomplete for evaluating the primary endpoint. The registry title refers to Grade 3 and Grade 4 adverse events and serious adverse events, but the posted summary does not break out Grade 3 and Grade 4 counts. It reports serious and other adverse event counts without clarifying whether those categories overlap. The denominator and counting basis for listed serious-event term percentages are not reported in the registry record.

The record does not report confidence intervals, inferential tests, an adjusted analysis, a sample-size justification, or the statistical analysis plan. It also does not provide a missing-data strategy, participant flow after enrollment, reasons for early termination, or follow-up duration by participant. The safety population is defined as those who received at least one dose, but the reason the safety count differs from enrollment is not reported in the registry record.

Although several secondary outcomes are listed, their numerical results are not reported in the registry record, and there are no analysis entries. The record also does not report a death count. These limitations restrict assessment of precision, outcome completeness, and whether the posted safety summaries represent all prespecified analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multicenter, Safety Study Of Maraviroc — NCT00478231.
• Registry record last updated 2011-09-09; status last verified 2011-09.
• Results first posted 2011-08-08.
• 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 record describes NCT00478231, a completed Phase 3, multicenter, open-label, non-randomized, single-group safety study of maraviroc in people with HIV infection or AIDS. Enrollment was 209. The primary endpoint concerned Grade 3 and Grade 4 adverse events and serious adverse events from baseline to 30 days post-week 96 or early termination. The safety analysis set comprised participants who received at least one dose.

The posted safety counts list 34 participants with serious adverse events and 185 with other adverse events, among 206 at risk in each category. Selected serious adverse event terms and percentages are listed, but the record does not provide separate Grade 3 and Grade 4 counts, inferential analyses, confidence intervals, or numerical results for the listed secondary outcomes. The study began in 2007-07 and had primary completion in 2010-08.