Effects of Body Mass Index on the Hyperemic Response to Regadenoson: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Body Mass Index on the Hyperemic Response to Regadenoson (NCT00859833), a na na study. The primary outcome is Myocardial Perfusion Reserve Measured by Quantitative Perfusion MRI (Ratio of Myocardial Blood Flow During Stress Over Myocardial Blood Flow at Rest).

2. Clinical Question

3. Trial Design

The registry describes a completed, single-group study sponsored by the University of Utah. It lists the study start as 2009-02 and primary completion as 2010-07. The phase is recorded as NA. The design is not a randomized parallel-group comparison: allocation is listed as NA and the model as single-group. Participants had MRI measurements at rest and during sequential administration of two coronary vasodilators.

The brief summary describes a prospective, open-label comparative trial. It says measurements were taken in the same sequence for each participant during a two hour MRI exam: resting blood flow, blood flow during weight-adjusted adenosine infusion, and then blood flow during a single fixed dose of regadenoson. The registry classifies masking as SINGLE, while the summary calls the study open-label; the registry record does not explain this difference in wording.

The summary describes recruiting 32 subjects, with the first 2 used for protocol testing and then 30 subjects with BMI between 18 and 40. The enrollment field lists 30. These entries do not match, and the registry record does not reconcile them. The endpoint population is described as per protocol: all patients with analyzable data were included. It also records that 2/30 patients had MRI technical problems that prevented analysis of their data.

Because both drug measurements were collected sequentially in the same participants, the design permits a within-participant comparison in principle. However, the fixed order means changes associated with time, sequence, or the earlier measurement cannot be distinguished from differences associated with the drug. The registry record does not report a randomized order, a separate control group, or a parallel-group allocation.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis was per protocol. All patients with analyzable data were included. 2/30 patients had technical problems with the MRI data that made their data unable to be analyzed.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Myocardial Perfusion Reserve Measured by Quantitative Perfusion MRI (Ratio of Myocardial Blood Flow During Stress Over Myocardial Blood Flow at Rest), measured over 2 hours.

The primary endpoint is myocardial perfusion reserve measured by quantitative perfusion MRI. It is expressed as a ratio: myocardial blood flow during stress with a vasodilator divided by myocardial blood flow at rest. The registry describes measurements with each vasodilator, adenosine and regadenoson, and gives a timeframe of 2 hours. The endpoint is a continuous measure, with the mean and standard deviation identified as the intended summary statistics.

In general, a reserve ratio represents the stress blood-flow measurement relative to the participant’s resting flow. It is used in this study as an MRI-based measure of the hyperemic response to vasodilator administration. Considering a ratio rather than stress flow alone relates the stress value to the resting measurement, which is the endpoint’s stated construction. The registry describes first-pass gadolinium perfusion MRI as the measurement approach.

The record does not report the mean, standard deviation, or other numerical results for either drug condition. It therefore gives the endpoint definition but not the observed values needed to assess the size of the measured responses or the difference between them. The registry also does not report a threshold or equivalence margin that would define how close two responses must be to count as equivalent.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous and is summarized in the registry as a mean with a standard deviation. In general, a mean describes the average measurement in an analysis group, while a standard deviation describes the spread of individual measurements around that average. Neither statistic is reported as an observed result in the registry record. Without those values, the stated summary approach cannot be used to judge the distribution of measurements or the variability of the endpoint.

What does a within-participant comparison mean?

Because each participant was measured at rest and under both vasodilators, a natural comparison would use the two drug-condition measurements from the same participant. In general, paired analysis focuses on each participant’s within-person difference rather than treating the measurements as if they came from unrelated groups. This can reduce the influence of stable differences between people, such as baseline characteristics that affect both measurements. The registry identifies the single-group sequence but does not report whether the primary analysis used paired differences or describe the exact statistical method.

The measurements were collected in a fixed order, with adenosine before regadenoson. Pairing does not itself remove order effects. If the response changes over the course of the MRI exam, or if one measurement influences a later measurement, a contrast between the drugs may also reflect sequence or timing. In general, varying or randomizing order can help separate these influences from the treatment contrast; the registry record does not report such an approach. It also does not report a washout or other sequence-management details.

How should an estimate and confidence interval be read?

In general, an effect estimate gives the direction and size of a contrast, while a confidence interval gives a range of values compatible with the data and analysis under its assumptions. A narrow interval indicates greater precision than a wide interval, but precision is not the same as clinical importance or proof of equivalence. For an equivalence question, the interval is assessed relative to a prespecified equivalence margin. The registry record reports neither a contrast estimate nor a confidence interval nor an equivalence margin, so this framework cannot be applied to the observed study results.

A p-value, when used, describes how incompatible the observed data are with a specified null model under the assumptions of the analysis. It does not measure the probability that a hypothesis is true and does not indicate the size of an effect. The registry record does not report a p-value or the null hypothesis used for an inferential test. A conventional test for no difference would not, by itself, establish equivalence; a small difference can be statistically detectable yet still fall within an acceptable margin, while a non-significant result can reflect imprecision.

What do the sample-size assumptions represent?

The record describes sample-size illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not a description of the trial’s actual single-group, sequential design. The illustrations are not the study’s observed power, and they should not be read as evidence that the trial was designed or analyzed using a two-arm randomized comparison. No numerical sample-size illustration or the effect used for the calculation is reported in the registry record.

In general, sample-size planning asks how much information would be needed to detect an effect under stated assumptions. An illustration based on an observed effect is especially dependent on that estimate: a different assumed effect leads to a different planning requirement. Planning calculations do not show the probability that the completed study found a true effect, and they do not substitute for confidence intervals or endpoint results. The registry record does not report the original design calculation, its target effect, or a justification for the enrolled number.

Why can the distribution matter?

Mean-based methods often rely on assumptions about the sampling distribution or residual variation. In general, strong skewness, outliers, or over-dispersion can make simple model-based standard errors and intervals unreliable, particularly when the amount of data is limited. Over-dispersion means that variability is greater than a chosen model expects. Analysts may consider robust methods or models suited to the data, but the registry record does not report distribution checks, transformations, robust standard errors, or an alternative model. The endpoint’s mean and standard deviation are specified as summary statistics, not reported results.

Repeated measurements also require attention to within-participant dependence. In general, measurements from the same person are correlated, so treating them as independent can misstate uncertainty. Paired analyses or repeated-measures models can account for this dependence, depending on the data and estimand. The registry record does not identify a repeated-measures model, covariance structure, or exact contrast. The fixed sequence presents a further interpretation issue that cannot be resolved merely by modeling correlation.

What analysis details remain unknown?

The analysis population is described as per protocol, including all patients with analyzable data. The record notes that 2/30 patients had technical MRI problems that made their data unanalyzable. In general, excluding participants with unavailable measurements can affect the result if the reasons for missingness are related to the outcome or participant characteristics. The registry does not report why the technical problems occurred, whether missingness was considered informative, or whether imputation or sensitivity analysis was used.

The record lists one outcome measure and one analysis, but it does not describe the statistical model, covariate adjustment, standard-error method, handling of outliers, or inferential procedure. It also does not report a full statistical analysis plan. These omissions do not prove that no such methods were used; they mean that the methods are not reported in the registry record. Consequently, readers cannot reproduce the endpoint analysis or check whether its assumptions match the data.

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("Adenosine", "Regadenoson")
n   <- c(28, 28)
m   <- c(2.25, 2.44)
sp  <- c(0.59, 0.91)
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  Adenosine  28  2.250  0.590  2.021  2.479
CARM  Regadenoson  28  2.440  0.910  2.087  2.793

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. That count does not explain whether additional comparisons, subgroup analyses, or exploratory models were conducted. The primary endpoint is measured with each vasodilator, and the study question concerns response across body sizes. The registry record does not report how many statistical contrasts were examined, which one was designated for inference, or whether any adjustment for multiple testing was planned. A multiplicity strategy is not reported in the registry record.

In general, testing many hypotheses can increase the chance of finding an apparently unusual result by chance. Adjustment procedures can control specified error rates, but their use depends on which comparisons are considered part of a family of tests. With no reported list of planned tests or analysis plan, the extent of any multiplicity issue cannot be determined. The count of one listed analysis should not be taken as evidence that there were no other analyses.

The analysis population is described as per protocol and includes all patients with analyzable data. The registry notes that 2/30 patients had technical MRI problems that prevented analysis of their data. It does not report a separate intention-to-treat population, the number included in each condition-specific estimate, or any imputation procedure. It also does not describe how missing measurements were handled beyond the analyzable-data inclusion statement.

In general, missing-data methods rely on assumptions about why observations are unavailable. If missingness is related to the measurement or participant characteristics, an analysis limited to observed data can differ from the result that would have been obtained with complete measurements. The registry does not report an assessment of the missingness mechanism or sensitivity analyses. Thus the effect of the technical data problems on the primary analysis cannot be evaluated from the registry record.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry lists a single group titled Adenosine Followed by Regadenoson. For this group, it records 0 serious events among 30 at risk and 0 other events among 30 at risk. The deaths field is not reported in the registry record. No serious-event terms are listed.

These entries describe the adverse-event counts recorded for this group. They do not provide a comparison with an untreated or randomized control group, and they do not estimate a relative risk between treatment groups. The study’s sequential single-group design means that the safety figures cannot isolate which drug, if either, is associated with an event. The registry record does not report separate event counts by drug exposure.

In general, a recorded count of zero means no event was entered in that category for the listed group; it does not establish that the risk is absent. Safety estimates are also limited by the number of people observed, the way events were collected, and the observation period. The registry record does not provide additional details about event definitions, surveillance procedures, or event timing. The figures should therefore be read as registry-reported counts, not as proof of no risk.

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

The record establishes that the study set out to examine myocardial perfusion reserve under adenosine and regadenoson, with a stated interest in whether a fixed regadenoson dose produces equivalent hyperemia across a range of body sizes. It identifies MRI as the measurement method, describes the ratio used as the endpoint, and specifies a sequential single-group design. These details clarify the intended question and the measurement framework.

They do not establish the size, direction, or precision of any observed response. Numerical endpoint summaries and inferential results are not reported in the registry record. There is also no reported equivalence margin, so the hypothesis cannot be assessed against a defined threshold for acceptable difference. The registry record therefore does not support a conclusion that the responses were equivalent, nor a conclusion that they differed.

The study’s fixed sequence matters for interpretation. The same participants were measured first with adenosine and then with regadenoson, according to the summary. A within-person comparison can account for stable differences among participants, but without variation in order it cannot separate a drug contrast from potential order or time effects. The registry does not report an analysis addressing those effects.

The record also describes technical MRI problems that left some data unanalyzable and an analysis restricted to participants with analyzable data. It does not report missing-data sensitivity analyses or enough detail to determine how the excluded measurements might affect the estimate. Together with the absence of numerical endpoint results, this limits evaluation of both the estimate and its uncertainty.

The appropriate reading is therefore descriptive: the registry documents a completed study and its stated endpoint and design, but does not report the results needed to judge the central hypothesis. The safety counts are also descriptive and do not establish comparative safety. No treatment recommendation or clinical conclusion follows from the information reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a useful statistical question about comparing physiological measurements taken in the same participant. Within-participant designs can be informative because each person contributes measurements under both conditions, reducing the effect of stable differences between individuals. The central statistical task is to estimate the contrast between those paired measurements with uncertainty that accounts for their dependence.

The trial also illustrates that a paired design does not automatically remove every source of bias. Here, the drug sequence is fixed, with adenosine before regadenoson. If measurement values vary with time or sequence, those influences can be difficult to distinguish from a drug-related contrast. Design choices such as varying order can be important when the scientific aim is to attribute a difference specifically to the treatment condition.

Equivalence questions require a different interpretation from simply looking for a statistically significant difference. A conclusion of equivalence depends on a prespecified acceptable margin and sufficiently precise estimates relative to that margin. The registry record states an equivalence hypothesis but does not report a margin or numerical results. This makes the case a reminder that a clear scientific hypothesis needs a corresponding statistical definition and analysis.

Finally, the record shows why endpoint definitions and outcome results should be distinguished. It specifies myocardial perfusion reserve as a stress-to-rest blood-flow ratio and identifies the intended summary statistics, yet gives no numerical endpoint findings. Knowing what was measured is not the same as knowing what the measurements showed. A complete statistical interpretation requires the estimates, their uncertainty, and enough methodological detail to understand the analysis population and assumptions.

15. Limitations

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

The registry record does not report numerical primary endpoint results, including means, standard deviations, drug-condition contrasts, confidence intervals, or p-values. It also does not report an equivalence margin, so the stated equivalence question cannot be evaluated using the registry information. The statistical model and inferential procedure are not described.

The study is listed as single-group with allocation NA, and the summary describes the same measurement sequence for each participant. Because adenosine precedes regadenoson, treatment condition is tied to order. The registry record does not report randomization of order or an analysis that separates possible time or sequence effects from the drug contrast. It also does not report a separate control group.

The brief summary describes 32 subjects for recruitment, including 2 for protocol testing and 30 in the main group, while the enrollment field lists 30. The record does not reconcile these counts. It further notes that 2/30 patients had technical MRI problems that made their data unanalyzable. The analysis population is per protocol and includes analyzable data, but the record does not describe missing-data assumptions, imputation, or sensitivity analyses.

The summary calls the study open-label, while the registry masking field is SINGLE; the record does not clarify the difference. The registry also does not report how BMI was modeled, how the claimed range of body size was represented in analysis, or whether subgroup or interaction estimates were made. These reporting gaps limit assessment of reproducibility, precision, and the extent to which the central question was addressed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Body Mass Index on the Hyperemic Response to Regadenoson — NCT00859833.
• Registry record last updated 2011-05-24; status last verified 2011-05.
• Results first posted 2011-05-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00859833 is a completed University of Utah single-group study of MRI-measured myocardial perfusion reserve during sequential adenosine and regadenoson administration. The registry lists a study start of 2009-02 and primary completion of 2010-07. The primary endpoint is a continuous stress-to-rest myocardial blood-flow ratio, measured over a 2 hours timeframe.

The stated question concerns whether a fixed dose of regadenoson produces equivalent coronary hyperemia across people with different body sizes. The summary describes weight-adjusted adenosine followed by fixed-dose regadenoson, in the same sequence for each participant. The analysis is described as per protocol and limited to analyzable data; the record notes technical MRI problems for 2/30 patients.

The registry record does not report numerical endpoint results, an equivalence margin, or detailed statistical methods. It lists 0 serious events and 0 other events in the combined drug-sequence group, without a comparative control group.