This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effect of Raltegravir on Endothelial Function in HIV-Infected Patients (NCT00843713), a randomized phase 4 study. The primary outcome is Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00843713 |
| Phase | Phase 4 |
| Condition | HIV Infection, Inflammation, Cardiovascular Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 56 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
HIV-infected patients receiving long-term antiretroviral therapy are the population of interest. The trial description focuses on people with clinically undetectable HIV RNA levels. The registry record does not report further eligibility details or a more specific description of the participants whose primary endpoint results are posted.
Intervention
Raltegravir was added to participants’ current HIV medication. The active regimen was raltegravir 400 mg by mouth twice daily for 24 weeks.
Comparator
The comparator was a matching placebo pill, 400 mg by mouth twice daily for 24 weeks, alongside participants’ current HIV medication.
Primary question
The trial asked whether intensifying treatment with raltegravir was associated with a change in endothelial function, measured by brachial artery flow-mediated dilation (FMD). The primary endpoint was measured at 24 weeks and described as the change in brachial artery diameter from pre-treatment to post-treatment.
The research rationale described in the registry record is that cardiovascular risk in HIV infection may be related to inflammation and other pathways, and that the effect of HIV infection on cardiovascular risk is not fully understood. The trial’s stated aim was to assess whether adding raltegravir could affect endothelial function in people already receiving HIV treatment. The endpoint is a physiological measure, not a direct count of cardiovascular events.
The posted primary results are medians for the placebo and raltegravir groups, each accompanied by interquartile-range bounds. They describe the groups separately. The registry record does not report a between-group effect estimate, confidence interval, or hypothesis-test result for the primary endpoint, so the reported values alone do not establish the size or precision of a treatment contrast.
3. Trial Design
This was a phase 4, randomized, controlled trial with a parallel-group design. The registry record identifies quadruple masking. Participants were assigned to raltegravir or placebo, and each group continued its current HIV medication. The treatment period described for both groups was 24 weeks.
The registry record reports an enrollment of 56. The posted primary endpoint results include 30 participants in the placebo group and 26 in the raltegravir group. These are the group counts attached to the outcome results; the record does not explain whether they represent all randomized participants, all participants with endpoint measurements, or another analysis population.
Random allocation is used in general to reduce systematic differences between treatment groups at the start of a trial. In a parallel-group design, each participant is assigned to one study group rather than receiving both study treatments in sequence. Masking is intended in general to limit the influence of treatment knowledge on participant behavior, care, and outcome assessment. The registry record labels the trial quadruple-masked but does not specify which roles were masked or describe procedures for maintaining masking.
The active group received raltegravir 400 mg by mouth twice daily for 24 weeks in addition to current HIV medication. The placebo group received a matching placebo pill, also 400 mg by mouth twice daily for 24 weeks, in addition to current HIV medication. Thus, the stated comparison concerns adding raltegravir versus adding placebo on top of existing treatment, rather than replacing participants’ existing HIV medication.
The trial is marked completed. Its primary completion date is recorded as 2013-11, and its start is recorded as 2009-01. Further operational details, including the exact randomization procedure, allocation concealment, adherence assessment, and protocol deviations, are not reported in the registry record. A detailed account of the trial’s statistical analysis plan is also not reported in the registry record.
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
| Stage | Placebo | Raltegravir |
|---|---|---|
| STARTED | 30 | 26 |
| COMPLETED | 30 | 26 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Placebo | Raltegravir | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 26 | 56 | |
| Age, Continuous | Years | 53 (47 to 59) | 54 (47 to 59) | 53 (47 to 59) |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 29 | 24 | 53 |
| Race/Ethnicity, Customized: Caucasian | participants | 19 | 20 | 39 |
| Race/Ethnicity, Customized: African-American | participants | 5 | 3 | 8 |
| Race/Ethnicity, Customized: Latino | participants | 2 | 1 | 3 |
| Race/Ethnicity, Customized: Other | participants | 4 | 2 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD), measured over 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | millimeters |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is endothelial function measured by brachial artery flow-mediated dilation (FMD), with the result recorded in millimeters. The registry record describes the measure as the change in brachial artery diameter from pre-treatment to post-treatment and gives a timeframe of 24 weeks. The posted results are summarized with medians and interquartile ranges.
In general, FMD assesses how a blood vessel responds to a change in blood flow. It is used as a physiological measure of endothelial function: the endothelium is the inner lining of blood vessels, and its function is relevant to vascular regulation. This makes FMD a surrogate or intermediate measure for studying vascular biology. It is not itself a count of heart attacks, strokes, or other clinical cardiovascular events.
The placebo group’s posted median is 3.4 millimeters, with interquartile-range bounds of 2.4 and 5.1. The raltegravir group’s posted median is 2.9 millimeters, with bounds of 2.6 and 5.1. The record does not give a separate estimate of the treatment-group difference or explain how the change score was calculated beyond describing the pre-treatment and post-treatment measurements.
In general, a median represents the midpoint of an ordered set of observations, while the interquartile range describes the spread of the middle portion of the observations. These summaries can describe distributions without assuming that values are symmetrically distributed. They do not, on their own, quantify uncertainty in the difference between groups. For that, a comparative estimate and an uncertainty measure, such as a confidence interval, would be needed; those are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is a group-level descriptive summary at 24 weeks. The placebo group has a median FMD value of 3.4 millimeters, with interquartile-range bounds of 2.4 and 5.1. The raltegravir group has a median of 2.9 millimeters, with bounds of 2.6 and 5.1. These figures characterize the reported endpoint distributions in each arm; they are not a reported estimate of the randomized treatment effect.
A comparative interpretation would normally focus on the difference between groups, with an uncertainty interval and a statistical test or other prespecified inferential approach. The registry record does not report a comparative effect estimate, confidence interval, p-value, or an analysis for the primary endpoint. It is therefore not possible to describe the precision of a treatment contrast from the posted summaries alone. The group medians and their interquartile ranges should not be treated as substitutes for that missing comparison.
The registry labels the endpoint as a change in diameter between pre-treatment and post-treatment measurements. However, the record does not detail the specific analysis used to derive the posted values, such as whether the primary comparison used individual change scores or another approach. The record also does not report the distribution of baseline values, the endpoint values for individual participants, or an adjustment model. Those details matter when interpreting how a group summary relates to the randomized comparison.
The arm counts attached to the results are 30 for placebo and 26 for raltegravir. The overall enrollment is 56. Although these counts describe the posted endpoint results, the registry record does not identify the analysis population or explain whether participants without measurements were excluded. It also does not report missing endpoint counts or reasons for missingness. This limits assessment of whether the summaries represent all randomized participants or a subset with available data.
In general, randomization supports a causal comparison when outcomes are analyzed according to a suitable plan and missing data and other departures are addressed. Randomization does not by itself supply a treatment-effect estimate, nor does it resolve uncertainty caused by absent outcome data or incomplete reporting. Here, the available primary results remain descriptive. They do not establish the magnitude, precision, or statistical significance of a difference between raltegravir and placebo.
The endpoint is a measure of endothelial function, not a clinical cardiovascular event. Even a clearly estimated difference in FMD would answer a question about this physiological measure over the stated timeframe; it would not by itself quantify effects on cardiovascular events. The registry record reports no secondary outcome results, and no results for additional analyses are posted. Conclusions should therefore remain limited to the two arm-specific primary endpoint summaries and the details explicitly recorded.
9. Statistical Methods Explained
The reported results use medians and interquartile-range bounds for the primary endpoint. The outcome is brachial artery FMD in millimeters at 24 weeks, described in the registry record as a pre-treatment to post-treatment change in brachial artery diameter. The placebo group’s median is 3.4, with bounds of 2.4 and 5.1; the raltegravir group’s median is 2.9, with bounds of 2.6 and 5.1.
What does a median describe?
In general, the median is the central value after observations are ordered. Half the observed values lie at or below it and half at or above it, subject to ties and the conventions used for an even number of observations. A median is a measure of location, but it does not show every feature of a distribution. Two groups can have the same median and different spreads, or similar spreads and different medians.
The interquartile range, in general, describes the interval between the lower and upper quartiles. It gives a sense of the spread of the middle half of observations and is less influenced by extreme values than the full range. The posted endpoint summaries give bounds for each group, but do not provide the underlying observations or a confidence interval for a group median or for the difference between groups. The interval bounds should therefore be read as descriptive distribution summaries, not as uncertainty limits around a treatment effect.
Why is a between-group estimate important?
For a randomized trial, the treatment question concerns how outcomes compare between assigned groups. A direct contrast can be expressed as an effect estimate and accompanied by a confidence interval. In general, a confidence interval describes a range of values compatible with the data and the assumptions of the analysis at a stated confidence level. Its width reflects precision: a narrower interval indicates greater precision under those assumptions, while a wider interval indicates less precision. The registry record does not report a confidence interval or a comparative estimate for this endpoint.
A p-value, in general, summarizes how unusual data at least as incompatible with a specified null hypothesis would be under the statistical model and its assumptions. It is not the probability that a treatment has no effect, and it does not describe the size or clinical importance of an effect. No p-value for the primary comparison is reported in the registry record. Without the analysis plan and comparative result, the arm-specific medians cannot be used to infer statistical significance.
What can randomization and masking contribute?
In general, random assignment aims to make treatment groups comparable in expectation with respect to measured and unmeasured baseline factors. In a particular trial, chance imbalances can still occur, and randomization does not guarantee that every participant completes follow-up or has an observed outcome. The registry identifies this study as randomized and parallel, but does not describe the sequence generation or allocation concealment procedures.
Masking can reduce the risk that knowledge of assignment changes behavior, co-interventions, outcome assessment, or reporting. The registry record classifies the study as quadruple-masked, but does not identify the masked roles or explain the masking procedures. These labels describe the trial design as recorded; further details are not reported in the registry record.
What does the analysis population mean?
The number attached to an outcome summary may represent all randomized participants, only those with measured outcomes, or another defined population. In general, an intention-to-treat analysis compares participants according to their randomized assignment, regardless of adherence, whereas a complete-case analysis uses participants with observed outcome data. These approaches answer related but not identical questions and rely on different assumptions. The registry record gives outcome counts of 30 for placebo and 26 for raltegravir, but does not name the analysis population or state how missing measurements were handled.
Statistical methods also depend on the outcome’s distribution, design, and prespecified estimand. For example, a model may adjust for baseline measurement or other covariates, while a rank-based approach may be used for particular distributional reasons. These are general possibilities, not descriptions of the analysis in this trial. The statistical model, adjustment variables, handling of repeated measurements, and method for comparing arms are not reported in the registry record. It would be inappropriate to infer a method from the use of medians alone.
How should planning illustrations be read?
In general, sample-size planning asks how many participants would be needed to target a specified probability of detecting an effect under stated assumptions. Such planning depends on the assumed effect size, outcome variability, significance level, allocation, and analysis method. A planning illustration based on an observed effect is not an analysis of the trial’s achieved power, and it does not replace the estimate and confidence interval from the trial itself. The registry record does not report the original sample-size justification or the assumptions used for the trial’s own design.
More broadly, the registry record reports enrollment of 56 and an endpoint timeframe of 24 weeks, but does not report an analysis plan for the primary result. No interim-analysis plan or multiplicity adjustment is reported in the registry record. These omissions mean that the posted summaries can be described, but a fuller reconstruction of the trial’s inferential methods is not possible from the record alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure and reports no secondary outcome results. The number of posted analyses is recorded as zero. No multiplicity-adjustment approach, testing hierarchy, or family of hypotheses is reported in the registry record. Without a fuller analysis plan, it is not possible to determine how multiple outcomes, time points, or analyses were intended to be handled.
In general, multiplicity arises when several statistical questions are tested or estimated within a study. Repeated testing can increase the chance of at least one apparently notable result by chance. Study protocols may address this through prespecified priorities or statistical adjustments. These are general considerations; the registry record does not state whether such procedures were planned for this trial.
The primary endpoint results include 30 participants in the placebo group and 26 in the raltegravir group, while enrollment is 56. The registry record does not define the analysis population, state whether all randomized participants contributed to the primary outcome, report missing outcome counts, or describe reasons for missingness. It also does not report how missing data were handled. Therefore, the available counts do not establish whether there was complete outcome ascertainment.
In general, missing data can affect interpretation when the likelihood of an unobserved outcome is related to participant characteristics or outcomes. Methods for addressing missingness depend on the reasons data are absent and the assumptions used. No such assumptions or sensitivity analyses are reported in the registry record. Details of the primary analysis population, interim analyses, and statistical plan are also not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 1 | 30 | 3.3% |
| Raltegravir | 1 | 26 | 3.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 0 of 30 |
| Raltegravir | 1 of 26 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Raltegravir |
|---|---|---|---|
| Hepatocellular Carcinoma | Hepatobiliary disorders | 0 of 30 | 1 of 26 |
| Infection | Infections and infestations | 1 of 30 | 0 of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Raltegravir |
|---|---|---|---|
| Hyperbilirubinemia | Hepatobiliary disorders | 0 of 30 | 1 of 26 |
Serious events with the highest arm-level rate: hepatocellular carcinoma (3.8%), infection (3.3%).
The registry record reports serious adverse events affecting 1 of 30 participants in the placebo group and 1 of 26 participants in the raltegravir group. It reports other adverse events affecting 0 of 30 participants in the placebo group and 1 of 26 participants in the raltegravir group. These are participant counts as recorded; no comparative safety estimate or statistical test is reported.
In general, an adverse-event count is interpreted in the context of how events were defined, collected, and attributed, and of the duration of observation. The record does not provide further detail about event ascertainment, severity criteria, relationship to treatment, or the observation period for these safety summaries. It also does not report a method for comparing safety outcomes between groups. Counts alone do not establish whether a difference is due to treatment or chance.
The registry lists “Hepatocellular Carcinoma” at 3.8% and “Infection” at 3.3% among the top serious terms. The record does not provide additional context for these percentages in the posted results. Deaths are not reported in the registry record. These entries should be read as safety information recorded for the trial, not as a complete assessment of comparative risk.
12. What the Result Does, and Does Not, Mean
The result supports a limited descriptive statement: the registry reports a median FMD value of 3.4 millimeters for placebo and 2.9 millimeters for raltegravir at the 24-week endpoint, with interquartile-range bounds of 2.4 and 5.1 for placebo and 2.6 and 5.1 for raltegravir. The record describes the endpoint as a change in brachial artery diameter from pre-treatment to post-treatment.
Those arm-specific summaries do not show the estimated difference between randomized groups. The registry record does not report a confidence interval, p-value, or primary comparative analysis. Consequently, the size and precision of any treatment contrast cannot be determined from the posted endpoint summaries. The values should not be interpreted as proof of a difference or as proof that the groups are equivalent.
The trial’s question concerns endothelial function in treated HIV infection over 24 weeks. FMD is a physiological measure and is not a direct measure of cardiovascular events. The posted primary outcome therefore does not, by itself, answer whether treatment changes cardiovascular-event risk. The registry record’s stated rationale discusses inflammation and cardiovascular risk, but the posted results do not report comparative findings for those mechanisms or for secondary outcomes.
In general, a nonsignificant result would not establish equivalence, and an unreported test cannot be assumed to be nonsignificant. Equivalence or non-inferiority conclusions require prespecified margins and analyses, which are not reported in the registry record. Nor can clinical importance be inferred from a median alone without a defined interpretation of the endpoint and an estimated treatment contrast.
The trial is marked completed and reports enrollment of 56. The outcome counts are 30 for placebo and 26 for raltegravir, but the record does not specify the analysis population or the handling of missing measurements. These reporting gaps further constrain interpretation. The findings that can be described are the posted group summaries and safety counts; broader causal or clinical conclusions are not established by those summaries alone.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between describing each randomized group and estimating the effect of a randomized intervention. Group medians and interquartile-range bounds convey information about the observed endpoint distributions. A treatment question, however, requires a comparison between those distributions or another prespecified contrast, together with an assessment of uncertainty. The registry record reports the former but not the latter for the primary outcome.
The distinction is especially relevant for surrogate or intermediate measures. FMD provides a way to study endothelial function, a biological process connected to vascular health. In general, such a measure can be useful for research into mechanisms and physiological responses, but it is not interchangeable with clinical outcomes. The trial’s endpoint and timeframe define what the posted results can address; they do not by themselves quantify cardiovascular events.
The record also illustrates why the analysis population and missing-data handling matter. The endpoint summaries have group counts, but the registry does not explain whether these are all randomized participants or only those with observed measurements. Without that information, readers cannot fully assess the relationship between enrollment, follow-up, and the analyzed endpoint.
For biostatistical interpretation, the key reporting elements include a defined estimand, a comparative estimate, an uncertainty measure, and transparent methods for handling missingness and multiplicity. These details are not reported in the registry record. Their absence does not change the descriptive values, but it limits the strength and scope of conclusions that can be drawn from them.
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 principal limitation for interpreting the primary outcome is that the registry record reports arm-specific medians and interquartile-range bounds but no comparative treatment-effect estimate, confidence interval, or p-value. The record also does not describe the statistical model or provide enough detail to reconstruct the primary analysis.
The endpoint is described as a change in brachial artery diameter from pre-treatment to post-treatment, but the calculation and analysis of that change are not further specified. Baseline values, individual outcome data, and any adjusted analysis are not reported in the registry record. The analysis population is also not identified, despite the reported endpoint counts.
Missing-data amounts, reasons, methods, and sensitivity analyses are not reported in the registry record. The original sample-size justification, interim-analysis plan, and multiplicity strategy are also not reported. These gaps prevent assessment of how well the analysis followed a prespecified plan and how missingness or multiple testing may have affected inference.
The endpoint is a physiological measure assessed at 24 weeks, rather than a reported clinical cardiovascular outcome. The safety information consists of the posted adverse-event counts and listed serious-event terms; additional ascertainment and comparison details are not reported. The registry record does not provide further eligibility characteristics or specify which roles were masked. These limitations call for a narrow reading of the record: it documents the trial design and selected descriptive results, but leaves important details needed for a fuller statistical and clinical interpretation unreported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Raltegravir on Endothelial Function in HIV-Infected Patients — NCT00843713.
- Registry record last updated 2018-12-12; status last verified 2018-12.
- Results first posted 2015-06-10.
- 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.
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18. Record Summary
The registry record describes a completed phase 4, randomized, controlled, quadruple-masked, parallel-group trial of raltegravir intensification in treated HIV infection. Enrollment was 56. Participants assigned to raltegravir received 400 mg by mouth twice daily for 24 weeks alongside current HIV medication; the placebo group received matching placebo on the same stated schedule alongside current medication.
The primary outcome was brachial artery FMD at 24 weeks, described as change in diameter from pre-treatment to post-treatment and measured in millimeters. The placebo median was 3.4, with interquartile-range bounds of 2.4 and 5.1; the raltegravir median was 2.9, with bounds of 2.6 and 5.1. A comparative estimate and inferential analysis are not reported in the registry record.
Serious adverse events were reported for 1 of 30 placebo participants and 1 of 26 raltegravir participants. Other adverse events were reported for 0 of 30 and 1 of 26, respectively. The record does not report deaths, secondary outcome results, or details of missing-data handling and analysis populations.