NASH Fitness Intervention in Thrombosis Trial (NASHFit): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NASH Fitness Intervention in Thrombosis Trial (NASHFit) (NCT03518294), a randomized na study. The primary outcome is PAI-1 Level.

2. Clinical Question

3. Trial Design

NASHFit (NCT03518294) was a randomized, parallel-group trial with no masking. The registry lists the study as completed, with an enrollment of 28 and a primary completion date of 2021-03-24. The study began on 2018-06-01. Its phase is listed as NA, and Milton S. Hershey Medical Center is named as the sponsor.

Participants were assigned to standard of care or aerobic exercise. In the exercise group, the planned supervised program was 30 minutes of moderate-intensity exercise, 5 times per week. Standard-of-care participants were instructed to continue care as determined by their treating medical professional and maintain their current physical activity level. The record describes weekly phone calls to this group to check adherence. The masking status is none, so the study was open-label.

The primary endpoint was PAI-1 level, reported as a mean with standard deviation and measured at 5 months. The endpoint description defines change using the difference between baseline and 5-month measurements. The posted group summaries list 8 participants for standard of care and 16 for aerobic exercise. These endpoint-specific counts do not establish why they differ from the enrollment figure; reasons for missing endpoint data or the analysis population are not reported in the registry record.

The registry lists 11 secondary outcomes, including coagulation-related measures, adiponectin, and a PNPLA3 polymorphism. Numeric comparison summaries are available for three secondary biomarkers. Eligibility details, the allocation procedure, and the rationale for the planned enrollment are 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.

Before assignment: 31 patients were screened for this study. Three were excluded after screening (two declined and one was excluded because they were actively smoking)

Overall Study

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 PAI-1 Level, measured over 5 months.

The primary endpoint is PAI-1 level in ng/mL at 5 months, described as a measure of change in fibrinolysis. The registry says the change was calculated from measurements at baseline and 5 months. PAI-1 is used as a laboratory marker related to the balance between clot formation and clot breakdown, rather than as a direct count of clinical clotting events.

The group summaries report means of 151.4 with a standard deviation of 51.5 for standard of care and 176.2 with a standard deviation of 71.9 for aerobic exercise. These summaries describe the posted endpoint values but do not, on their own, give a between-group estimate of the difference in change. The registry record does not report a primary confidence interval, p-value, or sponsor-reported analysis. The values therefore should not be interpreted as establishing whether the groups differed in change from baseline.

A biomarker endpoint can help characterize biological responses, but it is not interchangeable with a clinical outcome such as a clotting event. The record’s stated broader interest is clotting risk in NAFLD; the posted primary measure addresses a related laboratory process over 5 months. It does not directly quantify the occurrence of thrombosis or establish what a biomarker change would mean for clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous, and the registry describes results using means and standard deviations. A mean gives the arithmetic average of the values in a group; a standard deviation describes how spread out individual values are around that average. A standard deviation is not a confidence interval and does not directly express how precisely the group mean or a between-group difference has been estimated.

A mean difference expresses the contrast between group means in the units of the outcome. For the secondary biomarker comparisons, the posted recalculations use the standard-of-care group as the reference and report the aerobic-exercise group relative to it. A negative estimate means the aerobic-exercise mean is lower in the direction of that contrast. It does not, by itself, indicate whether the difference is statistically persuasive, clinically important, or caused by the intervention.

A confidence interval gives a range of values compatible with the data and the calculation’s assumptions. In repeated use of the same method, intervals constructed this way have a stated coverage property. For an individual trial, the interval is useful for seeing both the estimated direction and the uncertainty around it. When an interval includes zero, the data do not distinguish a nonzero mean difference from no difference at the conventional two-sided 0.05 threshold. That does not demonstrate that the groups are identical: meaningful differences can remain compatible with a wide interval.

The unadjusted p-value measures how surprising the observed data, or data more extreme, would be under a null model of no mean difference, subject to the model assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of a difference. The secondary p-values are explicitly unadjusted recalculations from posted summary statistics. The registry record lists no sponsor-reported analyses for these comparisons.

The primary summaries do not yield a reported or estimable between-group comparison in the posted results. The record gives group means and standard deviations, but the comparison is marked as unavailable for a continuous endpoint. Accordingly, there is no primary recalculated mean difference, confidence interval, or p-value to interpret. The reason the primary comparison was not estimable is not reported in the registry record. The endpoint description refers to change between baseline and 5 months, but the posted summaries do not supply an inferential comparison of that change.

Planning figures for the secondary comparisons are illustrations based on the observed effect, not a reconstruction of the trial’s original design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Each planning value is a number of participants per arm. Planning for a smaller fraction of the observed effect requires a larger sample under these assumptions. Such figures depend on the observed effect, which can be unstable in a small trial, and should not be read as observed power or as evidence that a proposed future study will achieve its target. The registry record does not report the trial’s own sample-size justification.

Over-dispersion is a concern in count or rate outcomes when variability exceeds what a simple model assumes. It is not the central issue for these reported continuous mean comparisons. More generally, the choice of model should match the outcome type and its distribution. The record does not describe a statistical model, covariate adjustment, transformations, or diagnostics for the primary endpoint. Those methods are therefore not available for assessment.

Standard deviations and group means summarize the observed data but do not show whether missing measurements were related to treatment assignment or outcome values. The registry record does not report an imputation method, missing-data sensitivity analysis, analysis population, or handling of withdrawals. These omissions matter because complete-case summaries can be affected if the participants with available measurements differ systematically from those without measurements.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Standard of Care", "Aerobic Exercise")
n   <- c(8, 16)
m   <- c(151.4, 176.2)
sp  <- c(51.5, 71.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Standard of Care  8  151.400  51.500  108.345  194.455
CARM  Aerobic Exercise  16  176.200  71.900  137.887  214.513

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes, but it does not report a multiplicity strategy. It is not reported whether the outcomes were arranged in a testing hierarchy, whether a subset was designated for formal inference, or whether any adjustment was planned for testing several hypotheses. The secondary p-values available in the posted results are unadjusted recalculations. Without a reported plan for handling multiple comparisons, they should not be treated as family-wise error controlled evidence.

The primary endpoint summaries include group means and standard deviations, but a primary between-group analysis is not estimable from the posted results. The registry record does not state why. It also does not report an analysis population, such as whether analyses were intended to include all randomized participants or only those with complete endpoint measurements. Although endpoint-specific counts are listed, the reasons for the variation in those counts are not reported.

Missing-data methods are not reported in the registry record. There is no reported imputation approach, sensitivity analysis, or description of how incomplete follow-up was handled. The record also does not report exclusions after randomization or a comparison of participants with and without endpoint data. Without these details, it is not possible to assess whether the posted summaries represent the randomized groups comparably or whether missingness could have influenced the results.

Interim analyses, stopping rules, and the statistical analysis plan are not reported in the registry record. Their absence from the record should not be taken as proof that no such procedures existed; their presence or absence cannot be established from the posted information. The appropriate interpretation is limited to the outcomes and analyses that are actually reported.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: partial knee replacement (10.0%).

The registry lists serious adverse events for both groups. For standard of care, it reports 1 participant affected by a serious event among 10 at risk; for aerobic exercise, it reports 0 affected among 18 at risk. Deaths are listed as 0 in each group. The record also lists other adverse events, with 1 affected among 10 at risk in standard of care and 6 among 18 at risk in aerobic exercise.

The registry identifies Partial Knee Replacement as a top serious-event term at 10.0%. It does not provide enough context in the posted summary to attribute that term to a particular group or establish its relationship to study participation. The figures are descriptive event counts, not evidence that an intervention caused or prevented an event. The record does not report event-level timing, severity details beyond the serious-event classification, or a causal assessment. These safety summaries should be considered separately from the biomarker comparisons and do not establish comparative safety.

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

NASHFit addresses a biologically relevant question: whether an exercise intervention might influence markers related to clotting and fibrinolysis in people with NAFLD. The randomized parallel-group design is relevant to comparing assigned strategies, and the open-label format is clearly recorded. The posted outcome information, however, leaves substantial uncertainty about the primary comparison.

The group summaries for PAI-1 describe the endpoint values, but they are not accompanied by an estimable comparison of change, a confidence interval, or a p-value. They therefore cannot establish that aerobic exercise changed PAI-1 relative to standard care. The secondary biomarker comparisons also have broad confidence intervals that include zero. They do not establish a clear difference, and they do not show that a difference is absent.

These results do not directly answer whether exercise changes the occurrence of clotting events. PAI-1 and the listed secondary biomarkers are laboratory measures, while the study’s broader rationale concerns clotting risk and clinically important events. A biomarker finding, even if precise, would not automatically establish an effect on clinical outcomes. The registry record does not report a clinical thrombosis endpoint among the posted results.

The findings also cannot establish whether any biomarker pattern applies to all people with NAFLD. Detailed eligibility criteria and the specific genetic susceptibility criteria are not reported in the registry record. The endpoint-specific counts are limited, and the reasons for incomplete or differing outcome counts are unknown. The findings should be read as limited evidence from this completed trial, not as a definitive estimate of an intervention’s effect or as a basis for individual medical decisions.

14. Why This Trial Matters Statistically

This trial is statistically informative in part because it illustrates the difference between having group summaries and having an interpretable treatment comparison. Means and standard deviations describe observed endpoint values, but the primary result still requires an estimable contrast with uncertainty. Without that contrast, the posted PAI-1 summaries cannot answer the primary between-group question.

The secondary comparisons show why confidence intervals matter. Their point estimates are not enough to characterize the evidence: the intervals include zero and span a wide range of possible effects. A non-significant p-value does not prove no difference, particularly when precision is limited. Conversely, a point estimate in one direction does not establish a reliable effect.

The record also highlights the importance of distinguishing confirmatory from exploratory outcomes. Multiple biomarkers are listed, while the registry does not report a multiplicity plan. Unadjusted secondary results can help describe patterns, but should not be given the same evidentiary weight as a prespecified, adequately precise primary analysis.

Finally, planning illustrations based on observed effects are not equivalent to an original sample-size rationale and are not observed power. Their interpretation depends on explicit assumptions, and estimates from small samples can be unstable. Clear reporting of the analysis population, missing-data handling, and planned statistical methods would help readers judge the robustness of both primary and secondary findings.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting efficacy is that the registry record does not provide an estimable between-group comparison for the primary endpoint. Although group means and standard deviations are posted, there is no reported primary confidence interval or p-value, and the reason the comparison could not be estimated is not reported.

There is also limited information about participant selection. The study summary refers to an at-risk population genetically susceptible to advanced disease, but detailed eligibility criteria and the means of defining genetic susceptibility are not reported in the registry record. The posted record therefore does not fully establish which population the results represent.

The endpoint counts differ across the primary and secondary summaries, and the record does not explain the differences. Missing-data procedures, analysis populations, withdrawals, and adherence to the exercise program are not reported. Without these details, it is difficult to assess whether outcome availability or intervention participation influenced the results.

The trial was open-label, and no masking was used. The primary outcome is a laboratory biomarker rather than a direct clinical clotting outcome. Numeric results for only a subset of the listed secondary outcomes are available, and there is no reported multiplicity plan or sponsor-reported analysis for the secondary comparisons. Finally, the registry record does not report the original sample-size justification or a detailed statistical analysis plan. These limitations constrain the precision, completeness, and clinical interpretation of the posted results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: NASH Fitness Intervention in Thrombosis Trial (NASHFit) — NCT03518294.
• Registry record last updated 2023-02-03; status last verified 2023-01.
• Results first posted 2023-02-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NASHFit (NCT03518294) was a completed randomized, open-label, parallel-group trial sponsored by Milton S. Hershey Medical Center. It compared supervised aerobic exercise with standard of care in a study concerning NAFLD and clotting-related biology. The registry lists enrollment of 28 and a primary completion date of 2021-03-24.

The primary endpoint was PAI-1 level at 5 months, described as change from baseline. Group means and standard deviations are reported, but no estimable primary between-group analysis is available in the posted results. Three secondary biomarker comparisons have unadjusted recalculated estimates; each confidence interval includes zero. The registry record does not report multiplicity adjustment, missing-data handling, or the analysis population, so the findings warrant cautious interpretation.