Microvascular and Antiinflammatory Effects of Rivaroxaban Compared to Aspirin in Type-2 Diabetic Patients With Subclinical Inflammation and High Cardiovascular Risk: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Microvascular and Antiinflammatory Effects of Rivaroxaban Compared to Aspirin in Type-2 Diabetic Patients With Subclinical Inflammation and High Cardiovascular Risk (NCT02164578), a randomized phase 3 study. The primary outcome is Change in Post-ischemic Forearm Blood Flow.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, randomized, parallel-group trial with no masking. Its title is “Microvascular and Antiinflammatory Effects of Rivaroxaban Compared to Aspirin in Type-2 Diabetic Patients With Subclinical Inflammation and High Cardiovascular Risk.” The official title specifies low-dose aspirin and very high cardiovascular risk. GWT-TUD GmbH is listed as the sponsor.

The registry reports enrollment of 179. The trial started in 2015-04, primary completion was 2018-12-12, and the status is completed. The two treatment groups received rivaroxaban or aspirin, with the assigned regimens continuing through the 20-week primary phase and an additional 32-week extension phase.

The primary endpoint was assessed at baseline and week 20. The primary outcome summary reports 83 participants in the rivaroxaban group and 84 in the aspirin group. These outcome counts are not the same as the overall enrollment figure; the registry record does not explain the difference or describe how participants contributed to each analysis. The primary analysis population is identified as the Full Analysis Set, but its exact definition is not reported in the registry record.

The registry lists secondary outcomes covering forearm blood flow, pulse wave velocity, skin blood flow, major bleeding, and clinically relevant non-major bleeding. Some outcome names appear more than once in the registry listing. Eight secondary outcomes are posted, with six analyses reported across the posted results. The record does not provide enough information to infer the full analysis schedule or explain why the number of listed outcomes and analyses differs.

Randomization and a parallel-group structure support a between-group comparison, while the absence of masking is relevant when interpreting measurements and other trial procedures. The registry record does not report the randomization method, allocation concealment, the trial’s original sample-size assumptions, or detailed procedures for participant follow-up.

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: 179 patients were randomized to one of the two treatment groups, 89 to receive rivaroxaban and 90 to receive acetylsalicylic acid (ASA). In total, 73 patients were included in the extension period, 37 of them received rivaroxaban and 36 received ASA.

Treatment Period

Reasons for not completing this period:

Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set

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.

Population: Baseline characteristics were assessed for the full analysis set (n=179)

6. Primary Endpoint

The registry lists the primary outcome as Change in Post-ischemic Forearm Blood Flow, measured over Baseline and week 20.

The primary endpoint is the change in maximal post-ischemic forearm blood flow from baseline to week 20, measured in ml/100ml. The measurement is taken during reactive hyperaemia after five minutes of forearm ischemia, using venous occlusion plethysmography. The endpoint therefore describes a change in a continuous physiological measure rather than a count of clinical events.

The registry places this measure within the trial’s investigation of microvascular effects. In general, measuring change from baseline can describe how a physiological measure differs after treatment relative to its starting value. A between-group comparison of those changes addresses whether the observed changes differed between the randomized treatment groups. The measure’s relevance to the trial’s stated microvascular question does not by itself establish how well it predicts clinical outcomes; that relationship is not reported in the registry record.

The posted primary outcome summary gives mean changes of 3.6 for rivaroxaban and 1.0 for aspirin. The posted comparison is expressed as aspirin minus rivaroxaban, yielding a mean difference of -2.6 ml/100ml. Thus, in the posted summaries, the average change is higher in the rivaroxaban group. This description is limited to the measured endpoint and does not establish a difference in clinical events or patient health.

7. Results Posted in the Registry

• Aspirin: mean 1.00 versus 3.60 on control; difference -2.60 (95% CI -4.11 to -1.09), standardized effect d = -0.52; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Post-ischemic Forearm Blood Flow

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Aspirin: mean 1.56 versus 6.11 on control; difference -4.55 (95% CI -8.29 to -0.81), standardized effect d = -0.63; z-test p = 0.017.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aspirin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Pulse Wave Velocity

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Aspirin: mean 0.14 versus 0.02 on control; difference 0.12 (95% CI -0.03 to 0.27), standardized effect d = 0.25; z-test p = 0.111.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Aspirin and the control. The interval gives the range of effects that remain compatible with the data.

Change in Skin Blood Flow

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Aspirin: mean -6.01 versus 3.47 on control; difference -9.48 (95% CI -22.02 to 3.06), standardized effect d = -0.24; z-test p = 0.138.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Aspirin and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover vascular measurements at different follow-up times and bleeding outcomes. Across the posted continuous vascular results, the pattern is not uniform: the week-52 forearm blood-flow comparison points in the same direction as the primary comparison, while the other week-20 vascular comparisons do not show comparably clear evidence of a between-group difference in their unadjusted calculations. The reported secondary analyses also use different methods, and the results should be read in light of those methods and their differing analysis counts.

The secondary results can be viewed as context for the primary finding, but they do not independently confirm that a change in forearm blood flow corresponds to a broader clinical benefit. The week-52 forearm measure is the same type of physiological outcome at a later assessment; pulse wave velocity and skin blood flow are different measures. The registry record does not report a relationship between these measures or establish how they should be combined in an overall conclusion.

Unadjusted secondary comparisons carry less weight when several outcomes are examined because the chance of obtaining apparently notable results can increase across multiple tests. In general, multiplicity procedures can address this issue, but the registry record does not report whether an adjustment was planned or applied. The posted p-values should not be treated as if each were the sole primary test.

The registry lists 10 outcome measures and posts 8 secondary outcomes, with six analyses reported. Some outcome labels are repeated, including bleeding outcomes. The record does not explain the repeated labels or provide a complete accounting of all planned and analyzed secondary outcomes. This makes the secondary evidence best interpreted as a set of supporting observations rather than as a single, definitive pattern.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Post-ischemic Forearm Blood Flow
• Change in Pulse Wave Velocity
• Change in Skin Blood Flow
• Change in Skin Blood Flow
• Major Bleeding
• Major Bleeding
• Clinically Relevant Non-major (CRNM) Bleeding
• Clinically Relevant Non-major (CRNM) Bleeding

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous and is summarized by a mean and standard deviation in each group. The mean describes the average observed change; the standard deviation describes the spread of individual changes around that average. In general, the standard deviation is not the same as the uncertainty in the estimated mean. The registry reports standard deviations of 4.69 for rivaroxaban and 5.27 for aspirin, alongside the group means and sample sizes.

The displayed between-group estimate is a mean difference. Its direction depends on the order of subtraction: the registry’s comparison is aspirin minus rivaroxaban. A negative estimate therefore indicates a smaller average change in the aspirin group in these posted summaries. Stating the comparison order is essential; the sign alone does not identify which group had the larger mean.

The posted confidence interval for the unadjusted mean difference is -4.113 to -1.087. In general, a confidence interval describes the uncertainty around an estimate under a specified statistical procedure. Its width reflects the estimate’s precision: narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. The interval is attached to the unadjusted summary-statistic comparison, not to the reported ANCOVA estimate, for which the registry gives no estimate or confidence interval.

The registry’s reported primary analysis uses ANCOVA and gives p = 0.004. In general, analysis of covariance compares groups while accounting for one or more covariates. The registry record does not identify the covariates, model specification, assumptions, or how the baseline measurement was incorporated. It is therefore not possible to reconstruct the sponsor’s adjusted estimate from the posted result. The reported p-value is evidence about the compatibility of the data with the analysis’s null hypothesis, under that model; it does not quantify the size of the difference or its practical importance.

The separate unadjusted calculation uses only the posted group summaries. It gives an estimate of -2.6 ml/100ml, a 95% confidence interval of -4.113 to -1.087, and p < 0.001. This calculation does not reproduce the ANCOVA. It is useful as a transparent comparison based on the displayed means, standard deviations, and sample sizes, but it does not reveal whether adjustment for baseline or other covariates changes the estimate or its uncertainty.

The standardized effect size listed for the primary comparison is -0.521. In general, a standardized effect expresses a difference relative to a measure of variability, which can make the magnitude easier to compare across measures with different units. It does not replace the original-scale mean difference: the clinical and measurement context remains tied to ml/100ml and the endpoint definition. The registry record does not describe a threshold for interpreting this standardized value.

For secondary outcomes, the registry reports ANCOVA for the week-52 forearm blood-flow analysis and pulse wave velocity, and a Wilcoxon (Mann-Whitney) analysis for skin blood flow. In general, ANCOVA is a model-based comparison that can account for specified covariates, while the Wilcoxon rank-sum approach compares the distributions of ranked observations and does not require the same mean-based model. The specific models and assumptions are not reported in the registry record. The unadjusted calculations accompanying these outcomes are not substitutes for the sponsor’s reported analyses.

The p-value is not a measure of effect size or precision. In general, it summarizes how unusual data at least as incompatible with a null hypothesis would be under the assumptions of a particular analysis. A small p-value does not establish clinical importance, and a larger p-value does not prove that groups are identical. Interpretation should consider the estimated difference, its interval, the endpoint, and the analysis method together.

Different sample sizes appear across the outcome summaries. The primary outcome includes 83 and 84 participants; the week-52 forearm outcome includes 29 and 30. Other posted secondary outcomes also have their own analysis counts. These counts should be read as the numbers used in the particular outcome summaries, not as a complete account of participant flow. Reasons for differing counts, missing-data handling, and the relationship of each analysis set to the Full Analysis Set are not reported in the registry record.

General statistical practice also distinguishes prespecified primary analyses from secondary and exploratory comparisons. A primary endpoint usually anchors the main trial question, while multiple secondary comparisons may offer supporting or descriptive information. The registry record does not report a complete statistical analysis plan, so the intended hierarchy, prespecification status of each analysis, or any adjustment across tests cannot be established from the posted material.

11. Confidence Intervals and Precision

The unadjusted primary comparison is -2.6 ml/100ml, with a 95% confidence interval from -4.113 to -1.087. The interval lies below zero and describes uncertainty around the estimated difference in mean change, with the comparison defined as aspirin minus rivaroxaban. In practical terms, the posted summaries are compatible with a range of negative differences under the assumptions of this calculation, rather than only with the point estimate.

In general, a confidence interval is a way to express the precision of an estimate. It does not mean that a particular interval has a stated probability of containing the true effect after the data have been observed. Its interpretation depends on the method and assumptions used to construct it. The interval posted for the primary endpoint accompanies the unadjusted calculation; the registry reports no confidence interval for its ANCOVA result.

The primary group standard deviations, 4.69 and 5.27, indicate substantial spread in individual changes around the group means. The confidence interval reflects the precision of the group contrast, not the range in which most individual participants’ changes fell. The sample sizes used for the primary summary are 83 and 84, and the endpoint is measured in ml/100ml.

For the secondary outcomes, the displayed intervals vary in width and include or exclude zero, so their precision differs. The week-52 forearm result is based on smaller posted analysis counts than the primary result. A smaller analysis set can make estimates less precise, although the interval itself is the direct summary of uncertainty for the reported calculation. The registry record does not provide adjusted confidence intervals for the reported secondary analyses.

Precision should be considered alongside the outcome’s meaning and the analysis method. A confidence interval can quantify uncertainty in a statistical contrast without showing whether the difference is important to patients or whether it corresponds to a clinical outcome. The primary endpoint is a physiological measure, and its connection to clinical events is not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations expressed as participants per arm, because the primary outcome is continuous. They are not total-event counts. The registry’s original design assumptions and sample-size justification are not reported in the registry record; the planning figures instead use the observed effect as a reference.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations consider detecting the observed effect and fractions of that effect, including 75% and 50% of the observed effect. They do not establish what effect the trial was originally designed to detect.

In general, the 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is the true one and the analysis assumptions hold. The 90% power column describes the corresponding planning target with a higher chance of detection. These are design calculations, not observed results, and they do not describe the probability that the trial’s conclusion is correct.

Smaller effects require more participants for the same power target, all else held constant. Accordingly, planning for 75% or 50% of the observed effect gives larger participant requirements than planning for the full observed effect. Because the observed effect itself may be uncertain, planning based on it is an illustration rather than a substitute for a prespecified design justification.

This is not observed power. The planning values answer a hypothetical design question about how many participants might be needed under stated assumptions; they do not measure the chance that the completed trial detected an effect after its results were known. The sample-size figures should be interpreted separately from the actual outcome counts and the reported trial analyses.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.600; pooled standard deviation σ = 4.990.
2. n = 2 × (1.96 + 0.842)² × 4.990² / -2.600² = 57.8, rounded up to 58 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.6                      # observed difference in means
sigma <- 4.99019092365667                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2164578)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 58 (80% power), 78 (90% power)
 75% of observed effect: n per arm = 103 (80% power), 138 (90% power)
 50% of observed effect: n per arm = 232 (80% power), 310 (90% power)
power.t.test: 58.8 
Simulated power at n = 58 per arm: 0.791 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as ANCOVA, with p = 0.004, and labels the analysis as superiority. It does not post the ANCOVA estimate, its confidence interval, the model specification, or the covariates used. The unadjusted recalculation from the posted group means, standard deviations, and sample sizes gives a mean difference of -2.6 ml/100ml, a 95% confidence interval of -4.113 to -1.087, and p < 0.001.

These results answer related but not necessarily identical statistical questions. The recalculation is a simple, unadjusted comparison of the displayed summaries. ANCOVA is a model-based analysis that can account for covariates, but the registry record does not state which covariates were included or how the model was fit. A difference between the reported p-values can arise when methods and assumptions differ; the posted information is insufficient to reproduce the ANCOVA or attribute the difference to a particular modeling choice.

The two analyses agree on the direction indicated by the posted group means: the aspirin group’s average change is lower than the rivaroxaban group’s. The recalculated confidence interval applies only to the unadjusted estimate. It should not be presented as uncertainty around the sponsor’s adjusted analysis. The registry record provides no basis for deriving an adjusted effect estimate or interval from the sponsor’s p-value alone.

The registry’s superiority label identifies the type of reported hypothesis test, but the record does not provide the full analysis plan or the prespecified decision criteria. The sponsor’s stated analysis and the unadjusted calculation should therefore remain clearly distinguished when interpreting the primary result.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified, but the registry record does not report a full statistical analysis plan. In particular, it does not state whether the secondary outcomes were prespecified in a formal hierarchy, whether one secondary outcome was considered more important than another, or whether a multiplicity adjustment was used. When many outcomes are tested, unadjusted p-values do not account for the increased opportunity for chance findings across the set. This is why secondary results should be interpreted cautiously and in context.

The record lists 10 outcome measures, posts 8 secondary outcomes, and reports six analyses. Some outcome labels are repeated. The registry record does not explain whether repeated entries reflect distinct assessments, separate analyses, or another organizational convention. It also does not specify how unreported listed outcomes should be interpreted.

The primary population is named as the Full Analysis Set, but the registry record does not define that population or explain how it relates to randomization and outcome availability. It does not report methods for handling missing measurements, whether any imputation was used, or how participants with incomplete follow-up were treated. The posted counts differ among outcomes, including between the primary week-20 outcome and the week-52 forearm outcome; reasons for these differences are not reported.

The registry record also does not report interim analyses, stopping rules, or the original sample-size justification. These details cannot be inferred from the completed status or the posted p-values. Their absence limits assessment of the full analysis strategy, but it does not by itself establish that a particular method was or was not used.

Given these reporting gaps, the primary result can be described using its posted analysis and the separate unadjusted calculation, while secondary results remain more difficult to place within a prespecified testing framework. The record does not support claims about missing-data robustness or family-wise error control.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: hypertensive crisis (2.2%), gastrointestinal hemorrhage (1.1%), escherichia sepsis (1.1%), osteoarthritis (1.1%), leiomyoma (1.1%).

The serious adverse event summary reports 89 participants at risk in the rivaroxaban group, with 4 affected, and 90 at risk in the aspirin group, with 6 affected. Deaths are reported as 0 in each group. The registry also reports 0 participants affected by other adverse events in each group. These are posted counts and should be read as a description of the recorded safety data, not as a complete comparison of risks.

The listed serious-event terms and percentages are hypertensive crisis at 2.2%, gastrointestinal hemorrhage at 1.1%, Escherichia sepsis at 1.1%, osteoarthritis at 1.1%, leiomyoma at 1.1%, and syncope at 1.1%. The record does not specify the arm attribution for these listed terms in the posted summary, so the percentages should not be assigned to a treatment group.

In general, counts of participants with serious adverse events do not alone establish that treatment caused an event or that the groups differ reliably in safety. Interpretation also depends on event definitions, exposure and follow-up, and the completeness of reporting. The registry record does not provide enough detail to assess those elements or to infer comparative safety from the counts alone.

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

The primary posted result describes a difference between the average changes in post-ischemic forearm blood flow in the two randomized groups at week 20. The observed mean change was higher in the rivaroxaban group than in the aspirin group, and the unadjusted comparison has a confidence interval entirely below zero when expressed as aspirin minus rivaroxaban. The registry’s reported ANCOVA analysis is labeled as superiority and has p = 0.004.

This result does not, by itself, show that one treatment improves health or prevents cardiovascular events. The endpoint is a physiological measure of forearm blood flow, not a clinical event. The registry record does not report whether changes in this measure predict patient-important outcomes or how the observed difference should be interpreted clinically. No treatment recommendation follows from the statistical comparison.

The finding also does not mean that every participant had a change matching the group average. The standard deviations indicate variation in individual measurements, and the estimated group difference is subject to uncertainty. The confidence interval characterizes uncertainty for the unadjusted comparison; it is not a range containing every participant’s response and is not the confidence interval for the sponsor’s ANCOVA result.

The secondary outcomes provide additional measurements but do not form a single confirmatory conclusion in the absence of a reported multiplicity plan. Their varied directions, follow-up times, methods, and analysis counts call for cautious interpretation. Likewise, the serious adverse event counts describe posted events but do not establish a causal or definitive comparative safety result.

The most defensible reading is therefore specific: the posted week-20 summaries show a between-group difference in mean change for the primary physiological endpoint, with the registry reporting an ANCOVA p-value and the unadjusted summary comparison showing its own estimate and interval. The result is not a substitute for evidence about clinical outcomes, the complete analysis plan, or the broader balance of benefits and risks.

18. Why This Trial Matters Statistically

This trial raises several statistical issues that are common in clinical research. The primary endpoint is a continuous physiological measurement, so interpretation depends on understanding both the scale of the mean difference and the variability of individual changes. Reporting the difference in ml/100ml alongside a confidence interval makes the magnitude and uncertainty more interpretable than a p-value alone.

The posted primary result also illustrates why analysis methods matter. The registry reports ANCOVA, while the recalculation from group summaries is unadjusted. Both can be useful descriptions, but they are not the same analysis, and the registry does not give enough model detail to reproduce the adjusted result. A reported p-value without its estimate and interval provides limited information about the size and precision of the sponsor’s analysis.

Follow-up and analysis counts are another important consideration. The primary and later forearm blood-flow summaries have different numbers of participants, and other outcomes have their own counts. Without participant-flow details and missing-data methods, readers cannot determine why those counts differ or how sensitive results might be to unavailable measurements.

The trial also reports multiple secondary outcomes across different measures and time points. Without a stated multiplicity strategy, individual secondary p-values should be treated as supporting or descriptive rather than as a set of independent confirmations. The posted secondary results do not all show the same degree of evidence, which reinforces the need to distinguish the primary question from additional analyses.

Finally, the primary endpoint concerns a physiological response, while the registry’s stated focus includes microvascular and antiinflammatory effects. Separating a measurement-level finding from conclusions about clinical outcomes is central to sound statistical interpretation. The record allows a focused reading of the endpoint comparison, but leaves important design and analysis details unreported.

19. 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 registry record does not report detailed eligibility criteria, so the extent to which enrolled participants represent the broader population of people with type 2 diabetes cannot be assessed from this record alone. The official title specifies very high cardiovascular risk and subclinical inflammation, but additional operational definitions and screening criteria are not reported.

The trial is listed as unmasked. The registry does not describe safeguards for measurement or other procedures that might be relevant when participants and investigators know the assigned treatment. The record also does not report the randomization method or allocation concealment, limiting assessment of those design features.

Important analytic details are missing. The ANCOVA model, its covariates, and the adjusted effect estimate and confidence interval are not reported. The Full Analysis Set is named but not defined. Missing-data handling, participant flow, and reasons for differing outcome counts are also not reported. The original sample-size justification and interim-analysis procedures are not reported in the registry record.

The primary endpoint is a physiological measurement rather than a clinical event, and the registry record does not establish its relationship to clinical outcomes. The secondary outcomes span several measures, time points, and analyses; a multiplicity strategy is not reported. These limitations constrain interpretation of the secondary findings and of any broader conclusions beyond the measured outcomes.

The safety summary contains group counts and a list of serious-event terms, but the registry record does not provide enough context to assess event attribution, exposure time, or completeness of adverse-event reporting. These limitations do not negate the posted results; they define what can and cannot be inferred from the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Microvascular and Antiinflammatory Effects of Rivaroxaban Compared to Aspirin in Type-2 Diabetic Patients With Subclinical Inflammation and High Cardiovascular Risk — NCT02164578.
• Registry record last updated 2023-11-07; status last verified 2023-01.
• Results first posted 2023-11-07.
• 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.

23. Record Summary

NCT02164578 is a completed, randomized, open-label, parallel-group Phase 3 trial sponsored by GWT-TUD GmbH. The registry reports enrollment of 179 and compares rivaroxaban with aspirin in patients with type 2 diabetes and high cardiovascular risk with subclinical inflammation.

The primary endpoint is change in post-ischemic forearm blood flow from baseline to week 20. The registry reports an ANCOVA superiority analysis with p = 0.004. The unadjusted comparison of the posted group summaries is -2.6 ml/100ml, with a 95% confidence interval from -4.113 to -1.087 and p < 0.001. The registry record does not provide the ANCOVA estimate or its confidence interval.

Secondary vascular results and serious adverse event counts are also posted, but the analysis plan, multiplicity approach, missing-data methods, and several design details are not reported in the registry record. The primary finding is specific to a physiological endpoint and should not be treated as evidence about clinical outcomes beyond those measured.