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 Dual Therapy With Raltegravir and Darunavir/Ritonavir in HIV Infected Patients. (NCT01258374), a registered phase not stated study. The primary outcome is Geometric Mean of C-Trough, of Raltegravir (RAL) at a Dose of 400 mg Twice a Day Plus Darunavir/Ritonavir (DRV/RTV) at a Dose of 800/100 mg Once a Day in HIV-1-infected Patients Were Mesured After 15 Days of Therapy..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01258374 |
| Phase | Phase not stated |
| Condition | Integrase Inhibitors, HIV; HIV PROTEASE INHIB |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hospital Clinic of Barcelona |
| Results posted | Yes |
2. Clinical Question
Population
HIV-1-infected patients receiving a nucleoside reverse transcriptase inhibitor-based regimen were considered. The record describes patients who were naive to raltegravir and had no evidence of protease inhibitor mutations by genotype test, with signed informed consent. The treating physician selected a nucleoside-sparing regimen because of toxicity or resistance mutations. The record states that 15 patients were screened and enrolled.
Intervention
The regimen combined raltegravir 400 mg twice daily with darunavir/ritonavir 800/100 mg once daily. The record describes the study as dual therapy and says patients had been on therapy for at least 15 days before the pharmacokinetic study.
Comparator
No comparator arm is described. The registry record lists one arm and does not state an allocation method. This is therefore not a randomized, like-for-like comparison of the dual regimen with another treatment or with continued nucleoside-based therapy.
Primary question
The listed primary outcome concerns the geometric mean of the raltegravir trough concentration, in ng/ml, after at least 15 days on the combination regimen. It is a pharmacokinetic question about drug concentration, not a direct comparison of clinical efficacy or tolerability. The numerical concentration result is not reported in the registry record. Although the study summary also describes an intention to explore plasma pharmacokinetics in a subgroup of 12 patients, the record does not state how many contributed to the primary outcome analysis.
3. Trial Design
The registry record identifies a completed, single-arm study sponsored by Hospital Clinic of Barcelona. It lists enrollment of 15 and gives the study start as 2010-05 and primary completion as 2011-05. The record describes one arm: raltegravir 400 mg twice daily plus darunavir/ritonavir 800/100 mg once daily. It does not state an allocation method, and no control arm is listed.
The primary outcome is a pharmacokinetic measure: the geometric mean of the raltegravir trough concentration. The timeframe states that, after at least 15 days on therapy, patients were admitted for a 24-hour pharmacokinetic study. The morning doses were administered in the clinic, and blood samples were scheduled immediately before breakfast and at specified times through 24 hours afterward. The record contains typographical errors in its description of this procedure, but the intended sampling schedule is stated.
The summary says the investigators also wanted to explore plasma pharmacokinetics in a subgroup of 12 HIV-infected patients. That statement describes an aim; the registry record does not report whether the subgroup was analyzed as planned or how many participants contributed data. It also does not report a sample-size justification, an interim analysis plan, or a detailed statistical analysis plan.
The investigators’ stated rationale concerned a nucleoside-sparing dual regimen for patients with toxicity or resistance, and their hypothesis referred to tolerability and effectiveness. However, the listed primary outcome is pharmacokinetic. The registry record does not report numerical primary outcome results or enough information to assess a comparative clinical effect.
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: The treating physician chose an NRTI-sparing regimen because of toxicity or resistance mutations to NRTIs, which included DRV/RTV 800/100 mg once daily plus RAL 400 mg twice daily. 15 patients were screenend and all of them were included and finish the study
Overall Study
| Stage | Single Arm With Dual Therapy |
|---|---|
| STARTED | 15 |
| COMPLETED | 15 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: HIV-1-infected patients, receiving a NRTI-based regimen, naive to RAL, with no evidence of PI mutations by genotype test, and signed informed consent forms. 15 patients ere screened and enrolled
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 | Single Arm With Dual Therapy |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | years | 44 (25 to 65) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 13 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 11 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 4 |
| Region of Enrollment: Spain | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean of C-Trough, of Raltegravir (RAL) at a Dose of 400 mg Twice a Day Plus Darunavir/Ritonavir (DRV/RTV) at a Dose of 800/100 mg Once a Day in HIV-1-infected Patients Were Mesured After 15 Days of Therapy., measured over After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Full Range |
| Unit | ng/ml |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the geometric mean of the raltegravir trough concentration, measured in ng/ml, after at least 15 days of raltegravir plus darunavir/ritonavir therapy. A trough concentration describes drug concentration at the low point in a dosing interval, so it is used in pharmacokinetic assessment to characterize drug exposure at that point. The record describes a 24-hour study with blood draws at baseline and scheduled times after the morning doses.
A geometric mean is commonly used for positive measurements such as drug concentrations when values are better described on a multiplicative or logarithmic scale than by an arithmetic average. This is a general statistical explanation; the registry record does not report the distribution of the observed concentrations or the analysis details used to calculate the geometric mean. The listed dispersion is the full range, which would describe the lowest and highest observed values if the results were reported.
The endpoint does not itself measure viral suppression, clinical progression, or comparative tolerability. While the study summary describes a broader interest in regimen effectiveness and tolerability, the record does not provide numerical results for those outcomes. The geometric mean and full range for the primary pharmacokinetic outcome are not reported in the registry record, so its magnitude and precision cannot be assessed from the reported result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a single-arm pharmacokinetic study, not a controlled trial comparison. Its primary question concerns raltegravir trough concentration after treatment with raltegravir plus darunavir/ritonavir. The record describes the regimen and sampling schedule, but it does not report the geometric mean concentration or its full range. Consequently, the posted record does not establish what concentration was observed or how variable measurements were in the participants who contributed to the outcome.
The enrollment figure is 15, but the number analyzed for the primary outcome is not reported in the registry record. The summary describes exploration of plasma pharmacokinetics in a subgroup of 12; this does not establish the number with complete concentration measurements or whether the primary outcome was calculated for that subgroup. The analysis population, exclusions from analysis, and handling of missing pharmacokinetic observations are not reported in the registry record.
The outcome is descriptive of drug exposure under the study regimen. Without a comparator, the record cannot support a direct contrast with another regimen. The study’s rationale and hypothesis mention effectiveness and tolerability, but those statements are not outcome findings. No numerical efficacy result is reported in the registry record, and no conclusion about clinical benefit can be drawn from the listed primary endpoint alone.
The adverse-event figures report zero participants affected in the serious adverse-event category and zero in the other adverse-event category, each among 15 at risk; deaths are also recorded as zero. These counts describe what the registry record reports, but they do not give the definitions, observation period, event-collection methods, or completeness of follow-up. They should not be read as proof that no event occurred outside the recorded categories or observation process.
Because the main numerical pharmacokinetic result is absent, neither its estimate nor its precision can be evaluated. In general, a confidence interval conveys the range of values compatible with an estimate under a specified method and assumptions. No confidence interval for the primary concentration is reported in the registry record. The small, single-arm enrollment and absent numerical endpoint results leave the main pharmacokinetic question unresolved within this registry record, while the lack of a comparator prevents a treatment-effect contrast.
9. Statistical Methods Explained
The methods need to be read in light of the outcome and design that are actually described. The record lists a single arm receiving raltegravir plus darunavir/ritonavir and a primary pharmacokinetic outcome. It does not report a randomized allocation, a control arm, the numerical outcome estimate, or a detailed statistical analysis plan. The explanations below describe general statistical ideas and distinguish them from methods explicitly documented in the registry record.
What does a geometric mean describe?
A geometric mean summarizes positive values after taking logarithms, averaging on that transformed scale, and returning to the original scale. This can be useful for drug concentrations when variation is proportional rather than additive, or when values are right-skewed. Those are general reasons for using a geometric mean; the registry record does not state why this summary was selected or whether any transformation-based model was used. It labels the primary measure as a geometric mean and the dispersion as a full range.
The full range refers to the minimum and maximum observed values. It can indicate the span of measurements, but it does not by itself show how observations are distributed within that span. It is also sensitive to extreme observations. Since neither the geometric mean nor the range is reported numerically, the record does not allow readers to assess the concentration level or observed spread.
What does trough concentration add?
A trough concentration is a pharmacokinetic measurement taken near the low point of a dosing interval. In general, trough measurements can help characterize exposure at that time in the dosing cycle. The record describes a 24-hour pharmacokinetic study after at least 15 days of therapy, with blood sampling from immediately before breakfast through 24 hours after the morning doses. It does not report the actual measured concentrations, the number of evaluable samples, or whether all scheduled samples were collected for each participant.
What can a single-arm design estimate?
A single-arm study can describe measurements observed among participants who receive the listed regimen. It cannot, by itself, estimate a between-regimen difference because there is no concurrent comparator group in the record. General causal comparisons require a suitable reference and assumptions about how groups were formed and measured. Here, the registry record lists one arm and does not state an allocation method. Thus, the primary outcome is appropriately read as a planned or reported within-regimen pharmacokinetic summary, not as a comparative treatment effect.
The record does not report a confidence interval or standard error for the primary concentration. In general, an interval estimate communicates uncertainty around an estimate under its statistical assumptions; its width depends on factors such as sample size and variability. Without a reported estimate, variability, or interval, the precision of the primary result cannot be judged. The stated enrollment does not substitute for the number with usable data for this particular outcome, which is not reported in the registry record.
How should planning calculations be understood?
The registry record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not evidence that the study used a two-arm design: the registry record lists one arm. Such illustrations are hypothetical sample-size scenarios and are not observed power. The record does not report the trial’s own sample-size justification, and no numerical planning outputs are reported in the registry record.
General sample-size planning asks how many participants per arm would be needed under specified assumptions to detect a chosen effect with a chosen power. The answer depends on the assumed effect, variability, significance level, allocation, and analysis. If the assumed effect is taken from an observed estimate, uncertainty in that estimate also matters. A planning calculation cannot demonstrate that a treatment effect exists, nor can it compensate for the absence of a comparator or a reported primary result.
What is not documented?
The registry record does not report the statistical test or model for the primary endpoint, the analysis population, missing-data procedures, or a multiplicity adjustment. It lists four outcome measures and one analysis, but does not give enough detail to determine how outcomes beyond the primary measure were handled. These omissions limit reproducibility and interpretation. They are gaps in the registry record, not evidence that a particular method was or was not used in practice.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists four outcome measures and one analysis, but it does not provide a complete account of the outcomes, their hierarchy, or the statistical procedures applied to each. It does not report whether formal adjustment for multiple outcomes or multiple statistical tests was planned or performed. Multiplicity matters in general because examining several outcomes or tests can increase the chance of a nominally unusual result arising by chance. Without the analysis details and numerical results, the impact of multiplicity cannot be evaluated for this study.
The primary outcome is identified as the geometric mean of raltegravir trough concentration. The record does not state whether a confidence interval, hypothesis test, or other uncertainty measure was calculated. It also does not describe the analysis population or the number of participants with usable measurements. The summary’s mention of a pharmacokinetic subgroup of 12 does not specify the analyzed population for the primary endpoint.
Missing-data procedures are not reported in the registry record. There is no description of incomplete sampling, unusable specimens, exclusions, or any method for handling missing concentration values. It is therefore not possible to determine whether the reported enrollment corresponds to the participants included in the endpoint analysis. The record also does not report an interim analysis plan or a detailed statistical analysis plan. These absences should be treated as limitations of what can be established from the registry record, not as evidence that no procedures existed.
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 |
|---|---|---|---|
| Single Arm With Dual Therapy | 0 | 15 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Single Arm With Dual Therapy | 0 of 15 |
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 |
|---|---|
| Single Arm With Dual Therapy | 0 of 15 |
The registry record reports zero participants affected in the serious adverse-event category, with 15 at risk. It also reports zero affected in the other adverse-event category, with 15 at risk, and records zero deaths. No serious adverse-event terms are listed. These are the counts recorded for the single arm; they are not comparisons with a control group.
Counts of zero are limited to the categories and observation process represented in the registry record. The record does not report the event definitions, the duration of safety follow-up, the method of collection, or whether all participants completed follow-up. It also does not provide event-level descriptions for the other adverse-event category. Without those details, the counts do not establish the completeness or sensitivity of event ascertainment.
The figures should therefore be read as reported counts, not as proof that the regimen is free of adverse events or as a comparative safety estimate. The registry record’s broader hypothesis included tolerability, but no detailed tolerability results are reported in the registry record. These safety counts alone cannot quantify risk or support a comparison with another treatment.
12. What the Result Does, and Does Not, Mean
The registry record describes a study of raltegravir plus darunavir/ritonavir in HIV-1-infected patients whose nucleoside-based regimen was being replaced because of toxicity or resistance. Its listed primary outcome is the geometric mean of raltegravir trough concentration after at least 15 days on therapy. The record also describes a 24-hour pharmacokinetic sampling schedule. These details identify the question the study was designed to address, but the numerical primary result is not reported in the registry record.
Accordingly, readers cannot determine the observed concentration, its full range, or its statistical precision from the registry record. The stated enrollment of 15 does not establish how many participants had complete pharmacokinetic data. The summary’s reference to a subgroup of 12 indicates an intended pharmacokinetic exploration, but it does not document the actual analyzed group or its result.
The study is listed with one arm and no comparator. It can therefore be described as an investigation of measurements under the dual regimen, but it cannot supply a controlled estimate of how the regimen compares with another treatment. The record’s background and hypothesis refer to potential effectiveness and tolerability, but those are not findings. The listed endpoint is a drug-concentration measure, not a direct clinical efficacy outcome.
The adverse-event entries record zero affected participants in both reported categories and zero deaths. These counts are limited by the safety information available in the registry record and do not establish comparative safety or rule out unrecorded events. Overall, the record documents the regimen, study population, and intended pharmacokinetic assessment, while leaving the primary numerical result, analysis population, and key details needed to judge precision and completeness unreported.
13. Why This Trial Matters Statistically
This study is statistically notable because the clinical rationale and the primary endpoint address different kinds of questions. The rationale discusses a nucleoside-sparing regimen in patients with toxicity or resistance, and the hypothesis includes tolerability and effectiveness. The listed primary outcome, however, is a pharmacokinetic summary: raltegravir trough concentration. Keeping those aims distinct prevents a concentration measurement from being mistaken for a clinical efficacy or safety result.
The single-arm structure also shapes what can be concluded. A within-arm pharmacokinetic description may characterize measurements under the regimen, but a treatment comparison requires a comparator. Since the registry record lists one arm and no allocation method, it does not offer a randomized contrast. This matters when interpreting any general claim about a regimen: a study’s rationale is not an estimate of comparative effect.
The record further illustrates why outcome reporting and precision information matter. A geometric mean and full range are named, but their numerical values are not reported in the registry record. Without those values, readers cannot judge either the concentration level or its observed variability. The number analyzed and the handling of incomplete measurements are also not reported. Enrollment alone cannot resolve those uncertainties.
Finally, the safety entries are counts, not a complete account of event ascertainment. The zero counts are informative as recorded but cannot replace definitions, follow-up details, or comparison data. Together, these features show how design, endpoint choice, missing reporting, and analysis population determine the strength and scope of a statistical interpretation.
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 interpreting the primary endpoint is that its numerical result is not reported in the registry record. Although the record names the geometric mean and full range, it does not give either value. Readers therefore cannot assess the observed raltegravir trough concentration, its spread, or its precision.
The study is described as a single arm, with no comparator and no stated allocation method. This limits the analysis to description of the regimen rather than a direct treatment comparison. The record does not report the number included in the primary analysis, whether all scheduled samples were collected, or how missing or unusable measurements were handled. The intended pharmacokinetic subgroup of 12 does not resolve those questions.
The registry record also does not report a detailed statistical analysis plan, the method used to calculate uncertainty, or a multiplicity procedure. While it lists four outcome measures and one analysis, the relationship between outcomes and analyses is not described in enough detail to assess the full analysis strategy. A sample-size justification for the trial is not reported in the registry record.
Safety interpretation is limited by the absence of reported event definitions, follow-up duration, and ascertainment details. The zero counts cannot be interpreted as a controlled safety comparison. The broader hypothesis mentions effectiveness and tolerability, but the listed primary endpoint is pharmacokinetic and numerical clinical results are not reported in the registry record. These limitations concern what can be established from the record and do not imply that unreported procedures or results did not exist.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dual Therapy With Raltegravir and Darunavir/Ritonavir in HIV Infected Patients. — NCT01258374.
- Registry record last updated 2019-09-27; status last verified 2019-08.
- Results first posted 2019-09-27.
- 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 record describes a completed, single-arm study sponsored by Hospital Clinic of Barcelona, with enrollment of 15. It lists raltegravir 400 mg twice daily plus darunavir/ritonavir 800/100 mg once daily for HIV-1-infected patients receiving nucleoside-based therapy and selected for a nucleoside-sparing regimen because of toxicity or resistance. The primary outcome is the geometric mean of raltegravir trough concentration in ng/ml after at least 15 days on therapy, assessed with a 24-hour pharmacokinetic study.
The record gives no comparator arm and does not report the numerical primary result, its full range, the number analyzed, or missing-data procedures. It reports zero participants affected in each of the serious and other adverse-event categories and zero deaths. Those counts are recorded without details on definitions or follow-up. The registry record therefore documents the study’s design and intended pharmacokinetic assessment, but the main numerical result and information needed to judge its precision are not reported in the registry record.