ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension (NCT05056896), a randomized early/phase 1 study. The primary outcome is Change of Intestinal Stem Cell Marker Gene Expression.

2. Clinical Question

3. Trial Design

ASPIRED-XT is registered as an early phase 1, randomized, double-masked, parallel-group study sponsored by Massachusetts General Hospital. The registry lists an enrollment of 161 and colorectal cancer as the condition. The study status is active, not recruiting. The listed start date is 2022-06-03, and the primary completion date is 2024-11-27.

The intervention groups are low-dose aspirin and placebo. Aspirin was administered daily at 81 mg, and the placebo group received a daily placebo capsule. Both descriptions specify treatment for the duration of the study up to 12 weeks. The primary outcome timeframe is 2 months. The registry lists secondary outcomes involving urinary PGE-M, urinary plasma GDF-15, colonic epithelial ChIP-seq and gene expression, and microbiome change.

Age is represented in the outcome groups: adults 18-55 years and adults 65 years or older, each with aspirin and placebo groups. For the primary endpoint, the registry reports results for 5 participants in the younger aspirin group, 7 in the younger placebo group, 7 in the older aspirin group, and 6 in the older placebo group. Those outcome groups comprise the stated analysis subset, not the full enrollment.

The registry does not report the detailed randomization procedure, allocation concealment, masking implementation, or the rationale for the enrollment target. Further protocol and statistical-plan details 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: Participants are screened for eligibility criteria by a member of the study staff and provide written informed consent prior to any research activities. Eligible and consented participants are stratified according to age group: younger (18-55 years of age) or older (65+ years of age), prior to randomization.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The primary outcome analysis was performed in 25 individuals who had available single-cell RNA sequencing data from at least 1,000 high quality EPCAM+ cells at both the pre- and post-treatment timepoint. This is a subset of the total study population. Randomization is preserved among those remaining in the final analysis and they are representative of the final study population. Future analyses will validate positive primary findings in the remaining study population using correlative approaches

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 Change of Intestinal Stem Cell Marker Gene Expression, measured over 2 months.

The primary endpoint is titled “Change of Intestinal Stem Cell Marker Gene Expression.” It measures the percent change in LGR5+ stem cells, using the proportion of cells expressing LGR5 among the intestinal stem cell cluster. For each participant, the registry describes calculating the change from the pre-treatment sample to the post-treatment sample. The reported timeframe is 2 months.

The analysis included individuals with pre-treatment and post-treatment samples that met the stated sequencing quality requirement: high-quality RNA sequencing reads from at least 1,000 EPCAM+ single cells per timepoint. Cells were clustered according to cell type before the LGR5+ proportion was calculated. The registry describes LGR5 as an accepted intestinal stem cell marker of stemness.

As a continuous measure, the endpoint retains information about the magnitude and direction of measured change rather than reducing the result to a yes-or-no outcome. In general, a cellular marker can serve as a biological measure relevant to a research question, but a change in a marker is not itself evidence of a change in cancer incidence or clinical outcomes. The registry does not report a direct colorectal cancer outcome as the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported mean represent?

The endpoint is continuous, and the registry reports the mean change in the proportion of LGR5+ cells for each age and treatment group. A mean is a measure of the center of the observed values. The group means can communicate the direction of average change, but they do not show how every participant changed. Here, the reported group means range from -9.1 to 6.4. The group-specific sample sizes are 5, 7, 7, and 6, so each mean is based on a limited number of analyzed participants.

The reported standard deviation describes the spread of participant-level changes around the group mean. It is not the same as the uncertainty around the mean. In general, a confidence interval for a mean or contrast combines information about variability and sample size to describe a range of values reasonably compatible with the data and the analysis assumptions. Such intervals are not reported for these group means.

What does linear regression contribute?

The registry identifies the analysis method as linear regression and reports p = 0.011 across the listed groups. In general, linear regression relates an outcome to explanatory variables through a model. Its interpretation depends on how the variables are encoded, which covariates are included, and which coefficient or joint hypothesis is tested. Those details, and the coefficient estimates, are not reported in the registry record. The p-value therefore cannot be translated into a particular aspirin-versus-placebo estimate from the information recorded.

A p-value is conditional on a null hypothesis and model assumptions. It measures how unusual the observed data, or data more extreme under the specified test, would be if that null hypothesis and model held. It is not an effect size and does not indicate how large a change is. It also does not establish that a result is clinically important. The absence of a reported confidence interval makes it especially difficult to evaluate the range of plausible values for a treatment contrast.

Why distinguish the groups?

The outcome is presented separately for adults 18-55 years and adults 65 years or older, with aspirin and placebo within each age category. This presentation matters because the group means differ in direction across the listed categories. In general, an overall treatment comparison and age-specific comparisons answer different questions. A model that uses all groups may test a hypothesis that is not equivalent to either age-specific contrast. Since the registry does not state the exact hypothesis tested by the regression, the reported p-value should not be assigned to one of these comparisons.

Random allocation can support fair comparisons when the analysis follows the randomized groups and missing outcome data do not compromise that balance. The registry says randomization is preserved among those remaining in the primary analysis subset. It does not give enough detail to assess how the subset was formed beyond the sequencing eligibility criteria or to determine whether missing paired data could have affected comparability.

How should the sample counts be read?

The full study enrollment is reported as 161, while the primary outcome analysis included 25 individuals with qualifying data at both timepoints. The group counts attached to the endpoint describe that analysis, not the total enrollment. In general, a smaller analyzed sample gives less information and can make estimates less precise. The posted record does not provide confidence intervals that would quantify this precision, nor does it state a sample-size justification for the endpoint analysis.

The record lists one reported analysis and six outcome measures. It also lists five secondary outcomes. The registry does not describe a multiplicity adjustment or a hierarchy for interpreting the outcomes. When multiple outcomes or comparisons are examined, chance findings become more likely unless the analysis plan accounts for that multiplicity. This is a general statistical consideration, not a claim that a particular adjustment was or was not used beyond what the record reports.

What do the planning illustrations mean?

Any planning illustrations based on the observed effect are prospective planning calculations, not evidence about what the trial had power to detect when designed. In general, such calculations depend on assumptions about the effect size, significance level, allocation, and statistical approximation. The registry record does not report the study's original sample-size justification or design assumptions. Planning illustrations should not be interpreted as observed power, as a reanalysis of the trial's design, or as a substitute for an estimate and confidence interval from the posted analysis.

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("Adults 18-55 Years of Age Randomized to Low Dose A", "Adults 18-55 Years of Age Randomized to Placebo", "Adults 65+ Years of Age Randomized to Low Dose Asp", "Adults 65 Years of Age or Older Randomized to Plac")
n   <- c(5, 7, 7, 6)
m   <- c(3.4, -9.1, -0.36, 6.4)
sp  <- c(7.6, 7, 12.2, 5.1)
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  Adults 18-55 Years of Age Randomized to Low Dose A  5  3.400  7.600  -6.037  12.837
CARM  Adults 18-55 Years of Age Randomized to Placebo  7  -9.100  7.000  -15.574  -2.626
CARM  Adults 65+ Years of Age Randomized to Low Dose Asp  7  -0.360  12.200  -11.643  10.923
CARM  Adults 65 Years of Age or Older Randomized to Plac  6  6.400  5.100  1.048  11.752

11. Analyses Reported by the Sponsor

The registry reports the sponsor's analysis as linear regression across the four listed age-and-treatment groups, with p = 0.011. It does not report the model coefficient, confidence interval, or a clearly identified treatment contrast. The p-value therefore conveys evidence from the stated analysis but does not, by itself, quantify the difference between aspirin and placebo or identify which group comparison it concerns.

No recalculated two-arm comparison is estimable from the posted summary statistics, and the record does not provide the effect estimate and uncertainty needed for a direct comparison with the regression result. The sponsor's reported analysis should therefore be kept distinct from any simple comparison of group means. There is no reported discrepancy between the sponsor analysis and a recalculated result; a recalculated contrast is not available for this continuous endpoint.

The registry does not give enough detail to reproduce the regression analysis or determine its exact tested hypothesis. The sponsor result should be interpreted within those limits, without treating its p-value as a measure of effect size, precision, or clinical importance.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary outcome and five secondary outcomes. The secondary outcomes concern urinary PGE-M, urinary plasma GDF-15, colonic epithelial ChIP-seq, colonic epithelial gene expression, and microbiome change. The record reports one analysis for the primary endpoint and does not describe how the several outcomes were prioritized or how multiplicity was addressed.

In general, testing multiple outcomes or contrasts can increase the chance of observing a nominally small p-value even when no underlying effect exists. A prespecified hierarchy, multiplicity adjustment, or clear distinction between confirmatory and exploratory analyses can help readers understand how to interpret multiple tests. These details are not reported in the registry record, so it is not possible to determine whether the reported p-value was adjusted or how it was intended to relate to other endpoint results.

The primary endpoint analysis used 25 individuals with qualifying pre-treatment and post-treatment sequencing data. The eligibility description requires high-quality RNA sequencing reads from at least 1,000 EPCAM+ single cells per timepoint. The registry states that this is a subset of the total study population and that randomization is preserved among those remaining. It does not report the number of participants with unavailable or unusable samples by randomized group, the reasons for missing data, or a comparison of participants included and excluded from this analysis.

In general, analysis of participants with complete paired measurements can be vulnerable to selection bias if availability of usable data is related to treatment assignment or outcome. The registry's statement about preserved randomization is relevant, but without details about missingness and the analysis population, the impact cannot be independently assessed. The record also does not report an imputation strategy, sensitivity analyses, or an intention-to-treat analysis for this endpoint. The statistical plan and sample-size justification are not reported in the registry record.

13. 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 non-serious adverse event terms

The registry reports zero serious adverse events in each of the four age-and-treatment groups. It lists 40 participants at risk in each of the younger groups, 41 in the older aspirin group, and 40 in the older placebo group. The reported counts of other adverse events are 16, 17, 21, and 17, respectively. These safety summaries are separate from the primary endpoint analysis, which used a subset of 25 individuals with qualifying sequencing data.

In general, an adverse-event count is a descriptive safety measure over the period and under the reporting definitions used in a study. A zero count of serious adverse events in a group means none were reported for that group in the registry record; it does not establish that the risk is absent. The record does not provide event descriptions for the other adverse events, severity, relatedness, timing, exposure-adjusted rates, or comparative statistical tests. No deaths are reported in any group.

These figures should be read as registry safety counts, not as a definitive comparison of safety between treatments. Differences in counts alone do not account for uncertainty, event characteristics, or duration of observation. The registry record does not provide further detail needed to characterize the adverse events.

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

The result concerns a short-term biological measure: change in the proportion of LGR5+ intestinal stem cells, reported as percent change over the 2-month timeframe. The posted group means and standard deviations describe the analyzed participants in the age and treatment groups. They do not directly measure colorectal cancer incidence, cancer risk over time, or a clinical outcome.

The reported linear regression p-value of 0.011 indicates a result from the sponsor's stated analysis, but the registry does not identify the specific contrast or provide an effect estimate and confidence interval. Without those details, readers cannot determine the size or precision of a treatment comparison from the p-value alone. The group means vary in direction, and the registry's result should not be reduced to a claim that aspirin increased or decreased the endpoint overall.

In general, a biomarker can help study biological processes, but a measured change in a marker does not necessarily predict a change in disease incidence or patient outcomes. Establishing that relationship requires evidence beyond the marker result itself. The registry describes the study as investigating a possible chemoprevention strategy, but the posted primary endpoint is not a colorectal cancer outcome.

The primary analysis was based on 25 individuals with qualifying paired sequencing data, rather than the full enrollment of 161. This limits how broadly the endpoint findings can be interpreted. The registry does not report confidence intervals, detailed missing-data analyses, or the exact regression contrast. Those omissions leave uncertainty about precision, the role of the age groups in the model, and the implications of the analyzed subset.

The appropriate interpretation is therefore bounded: the registry records group-level changes in a cellular marker and a regression p-value for the listed groups. It does not establish the magnitude of an aspirin-versus-placebo effect, whether the measured change is clinically important, or whether the intervention changes colorectal cancer risk.

15. Why This Trial Matters Statistically

This trial illustrates how a clinical study can enroll a larger population while its primary biological endpoint is available for a smaller subset. The registry reports enrollment of 161, but the endpoint analysis included 25 individuals who met the paired sequencing and cell-quality requirements. Keeping those populations distinct is essential: the analyzed sample counts describe the biomarker result, not the full randomized study population.

The endpoint also combines several layers of measurement. Single cells were clustered by cell type, and the proportion expressing LGR5 within the intestinal stem cell cluster was calculated at each timepoint before participant-level change was summarized. Each step helps define what the endpoint means, while also making the result different from a direct clinical outcome such as colorectal cancer incidence.

The age-stratified group summaries provide context for the reported regression p-value. Because the means differ in direction across the listed age groups, a single p-value without a specified contrast and model estimate is not enough to explain the treatment comparison. Clear reporting of contrasts and confidence intervals would help readers assess both magnitude and precision.

Finally, the record demonstrates why outcome multiplicity, missing paired measurements, and analysis-population definitions matter. The registry lists several outcomes but does not report a multiplicity strategy or detailed missing-data assessment. These are not merely technical details: they shape how much confidence readers can place in a nominal statistical result and how widely it can be applied. The posted information supports a careful description of the biomarker findings, while leaving important interpretive questions unresolved.

16. 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 endpoint limitation is that it is a cellular marker rather than a direct measure of colorectal cancer occurrence. The registry presents change in LGR5+ cells as the primary outcome, so the posted results do not establish whether cancer risk or clinical outcomes changed.

The primary outcome analysis included 25 individuals from the total study population. The registry specifies sequencing quality criteria but does not provide the number or characteristics of individuals who did not meet those criteria or lacked paired samples. It states that randomization is preserved among those remaining, but additional information would be needed to assess selection into the analysis subset.

The outcome groups are small, with group counts of 5, 7, 7, and 6. The registry reports means and standard deviations but no confidence intervals for the group summaries. The reported regression p-value is not accompanied by a coefficient, interval estimate, or an explicit description of the hypothesis tested. This limits assessment of the effect's size, precision, and specific treatment interpretation.

The age groups are reported separately, but the record does not explain how age was represented in the regression or whether the analysis tested treatment effects within age groups, an overall treatment effect, or another hypothesis. The statistical plan, multiplicity approach, sample-size justification, missing-data methods, and sensitivity analyses are not reported in the registry record.

Finally, the registry describes daily treatment for up to 12 weeks and gives a 2-month endpoint timeframe. The posted result is therefore limited to the recorded short-term endpoint and analysis. The record does not provide longer-term clinical outcomes or detail sufficient to infer how the biomarker findings relate to subsequent disease outcomes.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension — NCT05056896.
• Registry record last updated 2026-06-22; status last verified 2026-05.
• Results first posted 2026-05-15.
• 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.

20. Record Summary

ASPIRED-XT is a randomized, double-masked, parallel-group study of daily low-dose aspirin and placebo, registered as early phase 1. It lists colorectal cancer as the condition and describes the intervention as a possible chemoprevention strategy. The registry reports enrollment of 161, active-not-recruiting status, and a primary completion date of 2024-11-27.

The primary outcome is change in the proportion of LGR5+ intestinal stem cells, reported as percent change at 2 months. The analysis included 25 individuals with qualifying paired sequencing data. The group means differ across the age and treatment groups, and the registry reports a linear regression p-value of 0.011. It does not report the corresponding coefficient, confidence interval, or specific contrast.

The primary result is a short-term biomarker analysis, not a direct cancer outcome. Missing-data details, multiplicity methods, and the statistical plan are not reported in the registry record.