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 on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir (NCT03374358), a randomized phase 4 study. The primary outcome is Change in Liver Fat.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03374358 |
| Phase | Phase 4 |
| Condition | HIV Seropositivity, Metabolic Syndrome, Fatty Liver |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 45 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Helsinki University Central Hospital |
| Results posted | Yes |
2. Clinical Question
The clinical question is whether changing one component of an existing antiretroviral regimen is associated with a different change in liver fat over 24 weeks among people with HIV who are overweight or obese and have at least one metabolic syndrome component. The registry describes the switch as replacing a protease inhibitor or efavirenz with once-daily raltegravir while continuing the existing nucleoside analog reverse-transcriptase inhibitors. The comparison group continued its current regimen, including a protease inhibitor or efavirenz plus those other agents.
Population
People with HIV, body mass index over 25 kg/m2, and at least one metabolic syndrome component. The study concerns people whose current regimen included a protease inhibitor or efavirenz.
Intervention
Switch the protease inhibitor or efavirenz to once-daily raltegravir and continue the current nucleoside analog reverse-transcriptase inhibitors.
Comparator
Continue the current antiretroviral regimen, including a protease inhibitor or efavirenz plus nucleoside analog reverse-transcriptase inhibitors.
Primary question
What change in liver fat from baseline to 24 weeks is observed in each arm? The primary endpoint is the 24-week value minus the baseline value, measured as hepatic fat fraction by proton magnetic resonance spectroscopy.
The trial also planned to characterize body composition and metabolism. The registry identifies changes in subcutaneous and visceral adipose tissue volume, body weight, and total body fat as secondary outcomes. It describes subcutaneous tissue collection for future analyses of adipose tissue function. Those aims provide context for the study, but the primary result concerns liver fat. The posted primary results are descriptive arm-specific summaries; a formal between-arm estimate or test is not reported in the registry record.
3. Trial Design
This was a phase 4, randomized, parallel-group trial with no masking. The registry lists an enrollment of 45 and a completed status. The study began on 2018-01-10, and primary completion was recorded as 2019-11-02. Helsinki University Central Hospital is listed as the sponsor.
The two assigned strategies differed in whether the protease inhibitor or efavirenz was continued. Participants assigned to raltegravir switched that drug to once-daily raltegravir while continuing their current nucleoside analog reverse-transcriptase inhibitors. Participants assigned to the no-intervention control continued their existing antiretroviral regimens, including a protease inhibitor or efavirenz plus nucleoside analog reverse-transcriptase inhibitors. Thus, the registry describes a medication switch against continuation of the existing regimen, rather than a comparison with no antiretroviral treatment.
Randomization is a design method for allocating participants to study groups. In general, it can reduce systematic differences between groups at assignment, although it does not guarantee identical groups or remove uncertainty due to the number of participants and observed outcomes. The record does not report the randomization procedure or allocation concealment details. Because masking is listed as none, the trial is described as open-label; the record does not specify whether outcome assessment was masked.
The primary endpoint is change in liver fat between baseline and 24 weeks. The primary population is described as participants with data available at the specified time points. The registry reports 21 participants in the control arm and 18 in the raltegravir arm for the primary outcome. The registry record does not report why the analyzed numbers differ from the enrollment figure, or provide a participant flow account explaining exclusions or missing measurements.
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 | Control (= no Intervention Arm). | Raltegravir Arm. |
|---|---|---|
| STARTED | 24 | 21 |
| COMPLETED | 24 | 19 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Control (= no Intervention Arm). | Raltegravir Arm. |
|---|---|---|
| Withdrawal by Subject | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Only those participants with data available at the specified time points were analyzed.
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 | Control (= no Intervention Arm). | Raltegravir Arm. | Total |
|---|---|---|---|---|
| Participants analysed | 24 | 19 | 43 | |
| Age, Continuous | years | 50 (43 to 62) | 49 (39 to 54) | 49 (42 to 56) |
| Sex: Female, Male: Female | Participants | 5 | 4 | 9 |
| Sex: Female, Male: Male | Participants | 19 | 15 | 34 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 22 | 18 | 40 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Finland | participants | 24 | 19 | 43 |
| Liver fat content | % hepatic fat fraction | 3.1 (1.6 to 7.3) | 2.3 (1.1 to 6.0) | 2.3 (1.4 to 5.8) |
| Subcutaneous adipose tissue volume | mL | 5377 (3693 to 8237) | 3979 (2068 to 6468) | 4468 (2547 to 6146) |
| Visceral adipose tissue volume | mL | 2053 (1906 to 2886) | 1795 (1249 to 3164) | 1906 (1539 to 2349) |
| Body weight | kg | 98.8 (89.2 to 106.7) | 85.9 (76.1 to 97.7) | 93.2 (80.4 to 101.1) |
| Total body fat | kg | 30.0 (23.6 to 48.6) | 20.3 (14.6 to 29.7) | 23.8 (17.3 to 32.5) |
| Liver stiffness | kPa | 4.7 (4.1 to 5.5) | 4.1 (3.3 to 5.6) | 4.4 (3.6 to 5.5) |
| Fasting plasma glucose | mmol/L | 6.0 (5.7 to 6.3) | 5.5 (5.3 to 6.0) | 5.7 (5.5 to 6.3) |
| Fasting serum LDL cholesterol | mmol/L | 3.2 (2.8 to 3.5) | 3.2 (2.7 to 3.6) | 3.2 (2.7 to 3.5) |
| Fasting serum HDL cholesterol | mmol/L | 1.13 (0.98 to 1.28) | 1.30 (1.02 to 1.39) | 1.20 (1.01 to 1.39) |
| Fasting serum triglyceride | mmol/L | 1.3 (1.1 to 1.8) | 1.3 (1.1 to 2.2) | 1.3 (1.1 to 1.8) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Liver Fat, measured over Baseline and 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | % hepatic fat fraction |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in liver fat, defined as the 24-week value minus the baseline value. Liver fat is expressed as hepatic fat fraction, and the registry says it was measured by proton magnetic resonance spectroscopy. This measurement approach yields a numeric estimate of liver fat content, allowing the study to describe within-person change over the specified follow-up period.
The endpoint is reported as a median with inter-quartile range. A median describes the middle of an ordered set of observations and is less affected by extreme values than an arithmetic mean. In general, the inter-quartile range describes the spread of the middle half of observations. This can be useful when data are skewed or include extreme values, although the registry record does not report the underlying participant-level distribution.
Since the endpoint is calculated as the later measurement minus baseline, a positive value indicates a higher liver-fat measurement at 24 weeks than at baseline, while a negative value indicates a lower measurement. The reported group medians are 0.3 for control and 0.6 for raltegravir. Accompanying lower and upper figures are reported for each group, but no separate between-arm estimate or inferential test is posted. The endpoint therefore describes observed change within each arm; it does not by itself establish whether the groups differ beyond sampling uncertainty.
Liver fat was the primary focus because the stated objective was to examine whether switching antiretroviral treatment was associated with a change in liver fat among participants with metabolic risk factors. The registry also describes body composition and metabolic measures as additional interests.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is a change score, defined as the liver-fat value at 24 weeks minus the baseline value. The median change is 0.3 in the control arm and 0.6 in the raltegravir arm. Both medians are positive, so the typical reported change in each group is in the direction of a higher liver-fat measurement at follow-up than at baseline. These are arm-specific summaries, not a direct estimate of the difference between assigned strategies.
The registry also gives lower and upper figures for each arm: -0.5 and 2.7 for control, and -0.3 and 1.6 for raltegravir. The endpoint is described as a median with inter-quartile range, but the record does not label these figures more specifically. They should not be interpreted as confidence intervals: no confidence-interval description is given for them. The posted results do not include a formal comparison, a p-value, or a confidence interval for the between-arm contrast. Therefore the summaries alone do not show how precisely the difference between groups is estimated.
The number of participants with primary-outcome data is reported as 21 in control and 18 in raltegravir. The primary population is described as only those with data available at the specified time points. This means the result pertains to the available paired measurements as described in the registry, rather than documenting an analysis of every enrolled participant. The record does not explain the reasons for unavailable measurements or describe an imputation approach.
Random assignment is relevant to interpreting a comparison because, in general, it aims to make the assigned groups comparable at the outset. However, a causal interpretation depends on the conduct and analysis of the trial, including how missing outcomes and deviations from assigned treatment were handled. Those details are not reported in the registry record. The results are also limited to the specified population and follow-up period; the record does not establish what the measurements would be over a longer period or in populations outside the eligibility description.
These data are descriptive evidence about observed changes in liver fat in the two arms. They do not establish that either strategy caused a change, nor do they show whether any observed contrast is statistically distinguishable from chance variation. The registry lists two secondary outcome categories, but their numerical results are not included in the registry entries described for this analysis. The primary outcome should therefore be read on its own, without assuming that the broader metabolic aims were confirmed or not confirmed.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group comparison. In general, random assignment is intended to reduce systematic allocation differences between groups. It does not guarantee that the groups will be identical, and it does not replace reporting of baseline characteristics or the statistical comparison. The record lists no masking. It does not report the precise randomization method, whether allocation was concealed before assignment, or whether outcome assessors were masked.
What does the median describe?
The primary endpoint is summarized using a median and inter-quartile range. A median is the central observation after values are ordered. Unlike a mean, it is not pulled toward unusually high or low observations to the same extent. In general, median-based summaries are useful when the distribution is asymmetric or when extreme values are a concern. The registry does not give participant-level observations or a distribution plot, so the shape of the outcome distribution cannot be assessed from the reported summaries alone.
The inter-quartile range is a measure of spread around the median. In general, it spans the middle half of observed values and conveys how variable the measurements are within a group. The registry identifies inter-quartile range as the dispersion measure and reports lower and upper figures for each arm. It does not explicitly explain the meaning of those individual figures in the posted description, so they should not be relabeled as confidence limits or as another type of interval.
What does the change score mean?
The endpoint is calculated by subtracting the baseline liver-fat value from the 24-week value. This within-person change places the result in the direction of change over the stated period. A positive change represents a higher follow-up measurement than baseline; a negative change represents a lower follow-up measurement. The group medians are summaries of individual change scores. They are not the same thing as a comparison of the two groups, because a between-arm contrast would directly estimate how the change distributions differ.
In general, comparing changes between randomized groups can account for changes that occur over time in both groups, including changes unrelated to the assigned switch. A formal estimate of the between-group contrast, with an uncertainty measure and a stated analysis method, would be needed to quantify that comparison. The registry record does not report such an estimate or test for this primary outcome. No conclusion about statistical significance can be drawn from the arm medians alone.
Why does over-dispersion matter in general?
Over-dispersion occurs when outcome variability is greater than a statistical model assumes. In general, a model that understates variability can make uncertainty appear smaller than it is. This concept is especially relevant to count outcomes and other data that vary more widely than a simple model allows. The primary endpoint is a continuous change in liver fat and is reported with medians and inter-quartile range; the registry does not describe a model-based analysis or an over-dispersion assessment for it. This general issue should not be treated as a reported feature of this trial's analysis.
What do the planning assumptions say?
The registry includes planning-illustration assumptions based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These assumptions describe planning calculations, not the trial's own design justification or a measure of the certainty of its result. The record does not report the trial's sample-size justification. Planning sample sizes, where displayed, are illustrations and are not observed power. A sample-size illustration cannot supply a missing test, confidence interval, or comparison for the posted outcome.
The registry reports no analyses for the primary outcome in the information summarized for this record, and the posted values do not include an inferential comparison. The record also does not state whether a statistical analysis plan was finalized before the results were examined, which software or model was used, or whether any adjusted analysis was performed. Those omissions limit reconstruction of the analytic method. The quantities that can be read directly are the endpoint definition, its descriptive summary, the reported analyzed group counts, and the stated planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome of change in liver fat and identifies secondary outcomes concerning subcutaneous and visceral adipose tissue volume, body weight, and total body fat. It also notes aims involving body composition and metabolism. When a study examines multiple outcomes, the chance of finding an apparently notable result by chance can increase if many tests are conducted. In general, investigators may address this through a prespecified testing order, adjustment procedures, or careful emphasis on estimation rather than isolated significance tests. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an analysis plan for controlling multiplicity.
The primary-outcome population is described as participants with data available at the specified time points. The registry reports 21 participants in the control arm and 18 in the raltegravir arm for this endpoint. It does not report the reasons for missing baseline or follow-up measurements, the number excluded for each reason, or whether missingness differed between arms. It also does not describe imputation, sensitivity analyses, or an analysis that includes all randomized participants. In general, analyzing only available paired measurements can be affected if outcome availability is related to participants' measured or unmeasured characteristics.
The record does not specify whether analyses followed assigned treatment regardless of adherence, how treatment discontinuation or switching was handled, or whether any per-protocol analysis was conducted. It also does not report an interim-analysis plan. These items are not evidence that a particular method was or was not used; they are details not reported in the registry record. As a result, the posted summaries cannot establish how robust the findings are to missing data, multiple outcomes, or alternative analysis populations.
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 |
|---|---|---|---|
| Control (= no Intervention Arm). | 1 | 24 | 4.2% |
| Raltegravir Arm. | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Control (= no Intervention Arm). | 0 of 24 |
| Raltegravir Arm. | 0 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Control (= no Intervention Arm). | 20 of 24 |
| Raltegravir Arm. | 16 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Control (= no Intervention Arm). | Raltegravir Arm. |
|---|---|---|---|
| Acute pancreatitis | Gastrointestinal disorders | 1 of 24 | 0 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Control (= no Intervention Arm). | Raltegravir Arm. |
|---|---|---|---|
| Sleeping difficulties | Psychiatric disorders | 13 of 24 | 10 of 19 |
| Headache | Nervous system disorders | 8 of 24 | 9 of 19 |
| Gastrointestinal (diarrhoea, nausea) | Gastrointestinal disorders | 7 of 24 | 9 of 19 |
| Nervousness | Psychiatric disorders | 9 of 24 | 7 of 19 |
| Dizzyness | Nervous system disorders | 8 of 24 | 5 of 19 |
| Depressed mood | Psychiatric disorders | 7 of 24 | 5 of 19 |
Serious events with the highest arm-level rate: acute pancreatitis (4.2%).
The registry reports serious adverse events separately from other adverse events and gives at-risk and affected counts by arm. For serious adverse events, the control group has 24 participants at risk and 1 affected participant; the raltegravir group has 19 at risk and 0 affected participants. Deaths are reported as 0 in each arm. The listed top serious-event term is acute pancreatitis, with a reported figure of 4.2%. The registry information does not give a further breakdown that would establish how this term relates to the arm-specific serious-event counts, so it should be read as the reported term entry rather than assigned to a particular arm.
For other adverse events, the registry reports 20 affected among 24 at risk in control and 16 affected among 19 at risk in the raltegravir arm. These are counts of participants affected, not a direct comparison of event severity, duration, or causal relationship to treatment. In general, an adverse event occurring during a trial does not by itself establish that the study treatment caused it. The registry record does not provide details about event timing, recurrent events, exposure duration, relatedness assessments, or statistical comparisons. The counts should therefore be read as descriptive safety reporting, not as proof of a difference between regimens.
12. What the Result Does, and Does Not, Mean
The primary results describe liver-fat change over the study's stated period among participants with measurements available at baseline and 24 weeks. The median change was 0.3 in the control arm and 0.6 in the raltegravir arm. Since change is calculated as follow-up minus baseline, both medians point toward a higher follow-up measurement than baseline. The reported lower and upper figures show that the summaries include values on either side of zero, but their precise interval interpretation is not fully specified in the posted description.
These summaries do not answer whether the two assigned strategies differ reliably. The registry record does not report a between-arm estimate, a confidence interval for that contrast, or a p-value. No formal statistical conclusion should be inferred from comparing the medians by inspection. A direct comparison would need to quantify the difference between the groups and its uncertainty, with a clear account of the analysis population and assumptions.
The randomized design supports a comparison of assigned strategies in principle, but the interpretation remains bounded by the available registry entries. The primary outcome uses available paired measurements, and reasons for missing data are not reported. The record also does not describe adherence, treatment changes after assignment, or adjustment methods. Those gaps make it difficult to determine how the posted summaries relate to all randomized participants or to assess sensitivity to analytic choices.
The result does not establish that a switch caused liver fat to rise or fall, and it does not show that either regimen is superior or inferior. It is a descriptive summary in a specific population: people with HIV, body mass index over 25 kg/m2, at least one metabolic syndrome component, and an existing regimen including a protease inhibitor or efavirenz. The result also concerns the measured endpoint and follow-up specified in the registry; it should not be extended to other outcomes, treatment strategies, populations, or follow-up periods without relevant evidence.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it frames a treatment-switch question as a comparison of changes in a measurable metabolic outcome. The randomized parallel design distinguishes the strategy of switching a protease inhibitor or efavirenz to once-daily raltegravir from continuing the current regimen. That distinction matters: a change observed within one group may reflect more than the assigned intervention, while a direct between-arm comparison is designed to evaluate the relative changes under the two assigned strategies.
The primary endpoint is a continuous change score measured by proton magnetic resonance spectroscopy and summarized with medians and inter-quartile range. This makes clear that the analysis is concerned with both direction and variability of change, not only a single follow-up measurement. The available summaries show positive median changes in both arms, but without an inferential contrast they do not establish whether the groups differ. The distinction between describing each arm and estimating a treatment contrast is central to interpreting randomized trials.
The record also illustrates why analysis-population and missing-data information matters. The reported primary outcome includes only participants with measurements at the specified time points, and the registry does not explain unavailable data. That limitation affects how confidently a reader can connect the observed summaries to the randomized comparison. The presence of listed secondary outcomes also raises general questions about prespecification and multiplicity, which the record does not answer.
Finally, the registry separates the scientific objective from the evidence actually reported. It describes broader interests in adipose tissue, body composition, and metabolism, while the primary numerical information available concerns liver-fat change. Keeping those scopes distinct prevents a narrow result from being treated as a conclusion about all metabolic outcomes.
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 posted primary result is descriptive: arm-specific medians and accompanying lower and upper figures are reported, but a between-arm estimate, confidence interval, and p-value are not. The record therefore does not quantify the precision of the primary comparison. The lower and upper figures are not explicitly characterized beyond the endpoint's stated use of inter-quartile range, so they should not be treated as inferential uncertainty bounds.
The primary analysis is limited to participants with data at the specified time points. Although arm-specific analyzed counts are reported, the record does not explain missing measurements, withdrawals, protocol deviations, adherence, or treatment changes. It does not describe imputation, sensitivity analyses, or the treatment of participants who did not follow their assigned strategy. These omissions limit assessment of the extent to which the available-measurement summaries reflect the randomized groups.
The registry describes a phase 4 randomized, open-label, parallel trial, but does not report the randomization procedure, allocation concealment, baseline characteristics, or whether outcome assessment was masked. It also does not report the statistical analysis plan, model specification, adjustment strategy, multiplicity control, or any interim-analysis details. The sample-size justification is not reported in the registry record; the stated planning assumptions are illustrations rather than documentation of the trial's own design rationale.
The numerical results concern liver-fat change from baseline to 24 weeks. The record's broader aims and secondary outcome titles do not substitute for numerical findings on those outcomes. Generalizability is also bounded by the eligibility description and the treatment strategies studied. The registry does not report longer follow-up results in the registry record for this analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir — NCT03374358.
- Registry record last updated 2021-09-05; status last verified 2021-08.
- Results first posted 2021-07-07.
- 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
NCT03374358 is a completed phase 4 randomized, open-label, parallel-group study sponsored by Helsinki University Central Hospital. The study compared switching a protease inhibitor or efavirenz to once-daily raltegravir, while continuing nucleoside analog reverse-transcriptase inhibitors, with continuing the current antiretroviral regimen.
The primary outcome was change in liver fat from baseline to 24 weeks, measured by proton magnetic resonance spectroscopy and reported as median with inter-quartile range. The posted median changes were 0.3 for control and 0.6 for raltegravir. The registry describes the primary analysis population as participants with data at the specified time points and reports 21 control and 18 raltegravir participants for this outcome. A formal between-arm statistical comparison and its uncertainty are not reported in the registry record.