PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction (NCT02819440), a randomized phase 2 study. The primary outcome is Resting Energy Expenditure After 12 Weeks of Drug Therapy (kcal/Day).

2. Clinical Question

The study’s broader rationale is that obesity is associated with cardiometabolic consequences and that features such as insulin resistance, beta cell dysfunction, reduced metabolic rate, and impaired aerobic capacity may be intervention targets. The trial specifically examines whether tadalafil improves cardiometabolic health in people who are obese and insulin resistant. That statement describes the research question, not a conclusion about the treatment. The posted results must be interpreted as comparisons in this trial and do not by themselves establish broader clinical effects.

3. Trial Design

The registry identifies NCT02819440 as a completed phase 2 randomized trial with a parallel-group model and triple masking. The listed interventions were tadalafil and placebo. The study was sponsored by Vanderbilt University Medical Center. The registry records a start in 2016-07 and primary completion in 2020-06. Enrollment is listed as 141.

The arm descriptions state that participants would be randomized following screening, and describe daily oral treatment over 12 weeks beginning at baseline. They specify 20mg for both the tadalafil and placebo arms. The descriptions refer to 100 obese adult subjects in each arm, but the text is truncated in the registry record. The record does not explain how that planned arm description relates to the enrollment figure or to the participant counts in the posted endpoint results.

For the primary outcome, the posted arm summaries include 48 participants in the tadalafil group and 52 in the placebo group. These outcome counts are the basis of the posted comparison and should not be mistaken for the enrollment figure. The registry record does not report a participant flow account, the reasons participants may not appear in the outcome summaries, or an analysis-population definition. It also does not report further details about the randomization sequence or the practical steps used to maintain triple masking.

The primary outcome is reported at 12 weeks. Several secondary outcomes are also listed at that time point, including energy expenditure, DEXA, quality of life, and other measures. Numerical results are posted for some of these secondary measures, while other listed outcomes do not have numerical comparisons in the record. A more complete protocol or statistical analysis plan is not reported in the registry record, so the intended hierarchy and analysis procedures cannot be established from this information alone.

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: 141 participants passed our screening procedures and were enrolled however only 125 were randomized due to dropouts and scheduling conflicts. We allowed up to 30 days between the screening process and the baseline visit. Participants were assigned to a group after the baseline visit.

Overall Study

Reasons for not completing this period:

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 Resting Energy Expenditure After 12 Weeks of Drug Therapy (kcal/Day), measured over 12 weeks.

The primary endpoint is resting energy expenditure after 12 weeks of drug therapy, reported in kcal/day. Energy expenditure is a continuous measure of how much energy the body uses at rest over time. The registry describes measurement using a metabolic chamber protocol and says the value is statistically adjusted for the baseline measurement. Its description also uses the phrase “resting exercise energy expenditure” and identifies a measurement in kcal/min; the posted endpoint title and unit, however, refer to resting energy expenditure in kcal/day. The registry record does not clarify this wording difference.

Resting energy expenditure is relevant to the study’s stated rationale because reduced metabolic rate is identified among the features associated with obesity that may contribute to cardiometabolic risk. Measuring this outcome allows comparison of the group means after treatment, with the endpoint intended to represent energy use at rest rather than energy expenditure during physical activity. The posted data give a mean and standard deviation for each arm, along with a mean difference and confidence interval for tadalafil compared with placebo.

The endpoint is not a direct measure of every aspect of cardiometabolic health, nor does one measurement establish how a person will fare in other health outcomes. Its interpretation is limited to the construct and timing described in the record. The registry record does not report additional details about the chamber protocol, the exact baseline-adjustment model, or how the measurement was processed.

7. Results Posted in the Registry

• Tadalafil: mean 1,267 versus 1,268 on control; difference -1.00 (95% CI -59.33 to 57.33), standardized effect d = -0.01; z-test p = 0.973.

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.

Physical Activity-induced Energy Expenditure (kcal/Day)

• 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:
  • Tadalafil: mean 3,320 versus 3,269 on control; difference 51.00 (95% CI -261.54 to 363.54), standardized effect d = 0.06; z-test p = 0.749.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tadalafil and the control. The interval gives the range of effects that remain compatible with the data.

Dual Energy X-Ray Absorptiometry (DEXA) (g)

• 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:
  • Tadalafil: mean 47.00 versus 50.00 on control; difference -3.00 (95% CI -7.71 to 1.71), standardized effect d = -0.25; z-test p = 0.212.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tadalafil and the control. The interval gives the range of effects that remain compatible with the data.

Quality of Life Using the Medical Outcomes Study Short-Form Health Survey (SF-36) Physical Component Score

• 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:
  • Tadalafil: mean 52.70 versus 51.00 on control; difference 1.70 (95% CI -0.75 to 4.15), standardized effect d = 0.27; z-test p = 0.175.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tadalafil and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes cover several related but distinct domains: energy expenditure during physical activity, DEXA, quality of life, cGMP/NP ratio, maximal oxygen consumption, sexual function, and maximal exercise energy expenditure. The record includes numerical comparisons for physical activity-induced energy expenditure, DEXA, and the SF-36 Physical Component Score. Numerical comparisons for the other listed outcomes are not reported in the registry record.

Across the posted secondary comparisons, the confidence intervals include no difference between tadalafil and placebo. Their point estimates vary in direction and size, and the outcomes use different units and scales, so they should not be combined into a single overall effect. This pattern is broadly consistent with the primary result in the limited sense that the posted estimates do not give a precise separation between groups. It does not establish that the effects on all outcomes are identical, or that any effect is absent.

The secondary outcomes are less conclusive than a single prespecified primary comparison when their interpretation is not supported by a reported hierarchy or multiplicity procedure. Considering many outcomes creates more opportunities for apparently notable estimates to arise from sampling variation. The registry record does not report whether the original analysis adjusted for multiple comparisons, which outcomes were designated confirmatory, or whether these measures were intended as exploratory. The unadjusted results should therefore be treated as descriptive evidence rather than as a set of independent confirmatory tests.

These endpoints also measure different constructs. Energy expenditure, body composition, and quality of life do not serve as interchangeable substitutes for resting energy expenditure. A result on one cannot automatically verify or contradict a result on another. The secondary comparisons provide context about the range of outcomes recorded, but incomplete numerical reporting and the absence of a stated multiplicity plan limit what can be inferred from their collective pattern.

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

• Physical Activity-induced Energy Expenditure (kcal/Day)
• Dual Energy X-Ray Absorptiometry (DEXA) (g)
• Quality of Life Using the Medical Outcomes Study Short-Form Health Survey (SF-36) Physical Component Score
• Change in cGMP/NP Ratio After 12 Weeks of Drug Therapy
• Maximal Oxygen Consumption
• Sexual Function
• Maximal Exercise Energy Expenditure (kcal/Day)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference represent?

A mean difference subtracts the comparison group’s mean from the intervention group’s mean, using the direction specified for the comparison. For the primary outcome, the posted direction is tadalafil compared with placebo. A negative estimate therefore indicates a lower reported mean in the tadalafil arm than in the placebo arm, while a positive estimate would indicate a higher mean in the tadalafil arm. The estimate of -1.0 kcal/day is the observed contrast in the posted summaries, not a statement about each participant’s individual change.

Because resting energy expenditure is a continuous measure, a group mean condenses many individual observations into one summary value. The standard deviation describes how spread out individual measurements are around that group mean. It is not the uncertainty of the mean difference itself. The posted standard deviations are 133.0 kcal/day for tadalafil and 164.0 kcal/day for placebo; the comparison also reports a pooled standard deviation of 149.9 kcal/day. Such summaries help characterize the observed data, but do not reveal the full distribution or whether it contains outliers or important subgroups.

How should a confidence interval be read?

A confidence interval gives a range of values compatible with the data under the statistical method used. In repeated studies using the same method, intervals constructed in this way would capture the underlying parameter at the stated confidence level with the method’s long-run frequency. It is not a range containing a known proportion of individual participant outcomes, and it does not assign a probability to the true value after the data have been observed.

For the primary comparison, the 95% confidence interval runs from -59.33 to 57.33 kcal/day. It includes zero, the value representing no mean difference, and extends in both directions. This indicates that the estimate is not precise enough to rule out a range of differences. Whether any value in that range would be important in practice is a separate question; a threshold for meaningful change is not reported in the registry record.

What does the p-value add?

The unadjusted p-value of 0.973 describes how unusual the observed result, or a more extreme result, would be under a model that assumes no underlying difference and the test’s other assumptions. It is not a measure of effect size and does not show the probability that the null hypothesis is true. A large p-value does not prove equality, and a small p-value would not by itself establish clinical importance. Here, the estimate and its interval provide more direct information about direction and precision than the p-value alone.

The posted p-value is unadjusted. It does not account for the possibility that many outcomes or comparisons were examined. Since several secondary outcomes are listed, multiplicity is relevant when interpreting secondary findings. Whether the trial’s original analysis plan included a correction or a hierarchy is not reported in the registry record.

What does baseline adjustment mean?

Adjustment for a baseline measurement uses information recorded before treatment to account statistically for initial differences when estimating an outcome at follow-up. Such an analysis can differ from a simple comparison of follow-up group means, depending on the model and the relationship between baseline and follow-up values. The registry says that the primary measurement was adjusted statistically for baseline, but does not describe the model or report its estimate. The posted comparison is a simple unadjusted recalculation from the summary statistics, so it should be distinguished from the baseline-adjusted analysis described in the endpoint text.

Why do assumptions matter?

Statistical comparisons depend on assumptions about the outcome, variability, allocation, and the analysis method. The recalculated comparisons use the posted group means, standard deviations, and sample sizes. General methods for comparing means typically rely on an appropriate model for sampling variability and on observations that are sufficiently independent. The registry record does not provide diagnostics or enough detail to assess every assumption for the sponsor’s analysis.

Over-dispersion is a general concern when observed variability exceeds what a chosen statistical model expects. If variability is underestimated, uncertainty may be understated and confidence intervals may be too narrow; if it is modeled appropriately, the resulting uncertainty can better reflect the observed spread. The posted standard deviations describe variability, but do not on their own establish whether a particular model fit the data well. The registry record does not report a separate assessment of over-dispersion, distributional checks, or robustness analyses.

Finally, statistical significance and precision are not the same as practical importance. The study does not report a threshold for a clinically meaningful difference in resting energy expenditure. A reader can assess the estimated contrast and its interval, but cannot determine from the registry record alone how the full range of compatible values maps to a prespecified meaningful change.

11. Confidence Intervals and Precision

The primary estimate is -1.0 kcal/day, and its 95% confidence interval extends from -59.33 to 57.33 kcal/day. The interval includes zero, so the posted data do not distinguish the estimate from no mean difference under the usual interpretation of this interval. Its span also indicates that the study’s reported group summaries are compatible with differences in either direction. The point estimate alone should not be read as a precise estimate of the underlying difference.

Each group’s mean has uncertainty because it is estimated from a finite number of observations, and the standard deviations indicate meaningful variation among participants. The primary outcome summary includes 48 participants in the tadalafil arm and 52 in the placebo arm. The interval reflects uncertainty in the comparison rather than the range of individual participant values. It should not be interpreted as saying that individual measurements fall within its endpoints.

The endpoint description says the outcome was adjusted for baseline, but the registry does not report the sponsor’s adjusted estimate or its interval. The interval attached to the posted mean difference is therefore for the unadjusted recalculation based on the summary statistics. This distinction matters because adjustment can change the estimated contrast and its precision. Without the reported sponsor analysis, the registry record does not allow a direct assessment of the adjusted result.

Precision also depends on outcome variability, the number of observations contributing to the comparison, and the analysis method. The interval is informative about uncertainty in the estimated difference, but it does not establish which effects are important or exclude every possible effect. A clinically meaningful threshold is not reported in the registry record. Consequently, the interval can be described statistically, but its practical implications cannot be classified against a study-defined threshold.

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 based on the primary endpoint’s observed effect. They give participants per arm, not a total across both arms or a total number of events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. These are illustrations based on the observed result, not the trial’s original design assumptions; those original assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the stated effect under those assumptions. The 90% power column gives the corresponding per-arm number for a 90% chance. Power is a property of a planned study under specified assumptions, not a probability that the observed finding is true. The listed values are not observed power.

The planning rows refer to detecting 100%, 75%, or 50% of the observed effect. Smaller target effects require more participants under the same assumptions, because smaller differences are harder to distinguish from random variation. For the primary comparison, the observed difference is very small relative to the uncertainty, so planning from that effect yields very large participant counts. These figures should be read as sensitivity illustrations showing how assumptions about the effect size affect planning, not as a recommendation or as evidence about what the original trial was designed to detect.

The sample-size curve is another way to view the relationship between planning sample size and the stated effect assumption. It does not change the distinction between the trial’s observed outcome data and a future planning exercise. The registry record does not report the original sample-size justification, intended target effect, or original power calculation.

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 = -1.000; pooled standard deviation σ = 149.935.
2. n = 2 × (1.96 + 0.842)² × 149.935² / -1.000² = 352,891.9, rounded up to 352,892 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 <- -1                      # observed difference in means
sigma <- 149.934645626632                     # 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(2819440)
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 = 352,892 (80% power), 472,423 (90% power)
 75% of observed effect: n per arm = 627,364 (80% power), 839,862 (90% power)
 50% of observed effect: n per arm = 1,411,568 (80% power), 1,889,689 (90% power)
power.t.test: 352892.8 
Simulated power at n = 352,892 per arm: 0.797 (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. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study assesses several outcomes or makes several statistical comparisons. Even if each individual test uses a conventional threshold, the chance of at least one apparently unusual result can increase when many tests are considered together. Statistical plans commonly address this by identifying a primary endpoint, specifying a hierarchy, or using an adjustment procedure. The registry lists a primary endpoint and several secondary outcomes, but multiplicity procedures and the prespecified order of testing are not reported in the registry record.

The posted p-value for the primary comparison is unadjusted, and the posted secondary comparisons are also unadjusted. The registry record does not say whether the sponsor’s original analyses used any adjustment for multiple testing. Consequently, the secondary results should not be interpreted as a collection of independent confirmatory findings. The record also does not report a formal analysis plan or explain how the different secondary measures were to be interpreted together.

Missing data are another important uncertainty. The primary outcome summaries include 48 participants assigned to tadalafil and 52 assigned to placebo, while enrollment is listed as 141. The registry record does not give a participant flow account, the amount or pattern of missing endpoint data, reasons for non-availability, or methods used to handle missing observations. It is therefore not possible to determine from these summaries whether missingness could have affected the group comparison.

The analysis population is also not defined in the posted record. It does not state whether the primary comparison used all randomized participants, participants with an available measurement, or another population. The record does not report adherence summaries, protocol deviations, or sensitivity analyses for alternative missing-data assumptions. These omissions limit evaluation of how well the reported endpoint summaries represent all randomized participants and how robust the results are to incomplete follow-up.

These are reporting limitations, not evidence that a particular analysis was or was not performed. Without the protocol, statistical analysis plan, or a fuller results account, the intended multiplicity strategy, missing-data approach, and analysis populations remain unknown.

15. 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 serious adverse events for 0 of 61 participants at risk in the tadalafil group and 0 of 64 participants at risk in the placebo group. Deaths are listed as 0 in both groups. These figures describe the serious adverse event and death counts reported in the record; they do not establish that no other safety events occurred.

Other adverse events are reported for 36 of 61 participants at risk in the tadalafil group and 19 of 64 participants at risk in the placebo group. The record does not provide further detail about the event terms in this summary, their severity, duration, or relationship to treatment. It also does not report a statistical comparison of these counts. The counts should therefore be read as descriptive reporting, not as a causal estimate or a basis for concluding that one treatment is safer.

The number at risk in the adverse-event summaries differs from the group counts in the primary outcome summary. The registry record does not explain the difference, and the safety counts should not be assumed to represent the same analysis population as the primary endpoint. Interpreting safety requires attention to who was assessed, how events were collected, and the definitions used; further details are not reported in the registry record.

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

The posted primary comparison describes resting energy expenditure at 12 weeks in the trial groups. The group means are close, and the estimated mean difference is -1.0 kcal/day. The 95% confidence interval includes no difference and spans values in both directions. Together, the estimate and interval indicate that the posted summary does not provide a precise distinction between the groups on this outcome.

This is not proof that tadalafil and placebo have identical effects. A confidence interval containing zero means that no difference is among the values compatible with the statistical analysis; it does not rule out every potentially relevant difference. The registry record does not identify a threshold for a meaningful change, and it does not report the baseline-adjusted sponsor estimate described in the endpoint text. These limits prevent a definitive judgment about the practical importance of the full range of possible differences.

The result also does not establish what would happen for other measures of cardiometabolic health. Resting energy expenditure is one outcome, while the listed secondary measures address other dimensions. The posted secondary comparisons are not precise evidence of a clear separation either, but the absence of reported numerical results for several listed outcomes and the lack of reported multiplicity procedures limit an overall synthesis.

Interpretation is specific to this randomized phase 2 trial, its reported groups, and its 12-week assessment. The record does not give enough information about missing data, analysis populations, adherence, or the adjusted primary analysis to evaluate all aspects of robustness. Nor does a statistical comparison by itself establish broader clinical benefit, harm, or equivalence. The posted data describe what was reported for these trial outcomes; they do not warrant treatment advice or conclusions beyond the study question.

17. Why This Trial Matters Statistically

This trial is statistically informative because its primary estimate is paired with a confidence interval, allowing readers to distinguish the observed mean difference from the uncertainty around it. The estimated contrast is near zero, but the interval is broad enough to include differences in both directions. That combination illustrates why a point estimate alone is not an adequate summary of evidence.

The record also highlights the difference between an endpoint described as baseline-adjusted and a comparison recalculated from arm-level summary statistics. A baseline-adjusted analysis can answer a related but not identical statistical question to an unadjusted comparison of follow-up means. When the adjusted estimate and model are not reported, readers should keep that distinction visible rather than treating the recalculation as the sponsor’s primary analysis.

The sample-size illustrations make another statistical point: planning requirements depend strongly on the effect size a future study is intended to detect. The calculated figures based on the observed effect are very large, and smaller fractions of that effect require still larger groups under the stated assumptions. These planning numbers are not evidence that the trial had a particular power or that an effect is absent; they show how difficult it is to plan around a very small observed contrast.

Finally, the record lists multiple secondary outcomes but does not report a multiplicity strategy, missing-data approach, or analysis populations. Those omissions matter because statistical interpretation depends not only on estimates and p-values, but also on what was prespecified, who contributed data, and how multiple findings were handled. This makes the trial a useful example of reading numerical results alongside the limits of registry reporting.

18. 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 outcome description is not fully clear about the measurement wording: the title and unit identify resting energy expenditure in kcal/day, while the description refers to resting exercise energy expenditure measured in kcal/min. The registry record does not clarify this difference. The description also says the analysis was adjusted for baseline, but the adjusted estimate, model, and uncertainty are not reported. The posted mean difference is an unadjusted recalculation and may not reproduce the intended primary analysis.

The outcome summary includes fewer participants than the enrollment figure, and the registry does not reconcile these counts. It does not report participant flow, missing outcome data, reasons for missingness, or the analysis population. Adverse-event risk counts also differ from the primary endpoint counts, without explanation. This makes it difficult to determine how the outcome and safety populations relate to all randomized participants.

The registry identifies multiple secondary outcomes, but numerical results are not reported for every listed measure. It does not describe the multiplicity strategy, outcome hierarchy, original statistical analysis plan, or handling of missing data. The posted comparisons therefore cannot be assessed against a complete prespecified analysis framework.

Additional details that would support evaluation are not reported in the registry record, including the original sample-size justification, randomization procedures, masking procedures, adherence, protocol deviations, and sensitivity analyses. The arm descriptions are truncated, so not all treatment details are available. These reporting limits should be kept separate from the observed estimates: they do not change the posted numbers, but they constrain assessment of their robustness and scope.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction — NCT02819440.
• Registry record last updated 2022-05-27; status last verified 2022-05.
• Results first posted 2022-05-27.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT02819440 is a completed randomized, triple-masked, parallel phase 2 trial sponsored by Vanderbilt University Medical Center. It compared daily oral tadalafil with placebo over 12 weeks in a study focused on obese, insulin-resistant adults. Enrollment is listed as 141.

The primary endpoint was resting energy expenditure at 12 weeks. The posted mean difference for tadalafil compared with placebo was -1.0 kcal/day, with a 95% confidence interval from -59.33 to 57.33 kcal/day and an unadjusted p-value of 0.973. The registry describes baseline adjustment, but does not report the sponsor’s adjusted estimate.

Numerical results are also posted for selected secondary outcomes. The record does not report a full statistical analysis plan, multiplicity approach, missing-data methods, or analysis-population definitions. Those gaps limit assessment of the results beyond the posted summaries.