Cardiovascular Study of Lisdexamfetamine in Healthy and Hypertensive Attention Deficit Hyperactivity Disorder Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cardiovascular Study of Lisdexamfetamine in Healthy and Hypertensive Attention Deficit Hyperactivity Disorder Adults (NCT00753012), a na phase 4 study. The primary outcome is Left Ventricle Size.

2. Clinical Question

The study rationale centers on the cardiovascular effects of stimulant treatment in adults with ADHD. Its description notes concern about serious cardiovascular events reported among people treated with stimulants, while also stating that a definite link to stimulant use had not been established. The investigators anticipated changes in blood pressure and heart rate and proposed detailed cardiac testing as a way to examine cardiovascular effects.

The design does not establish a treatment contrast against an untreated or placebo group. It therefore addresses cardiovascular measurements in participants receiving lisdexamfetamine, rather than estimating a randomized treatment effect. Comparing the two hypertension-status groups would also not isolate the effect of hypertension or medication, because the groups were not randomized to those characteristics.

3. Trial Design

This was a completed phase 4 study sponsored by Massachusetts General Hospital. The registry describes a single-group model, no masking, and allocation as not applicable. Enrollment was 24. Participants were adults with ADHD, divided descriptively into normotensive adults and adults with primary hypertension treated with stable doses of antihypertensive medication. The record does not describe a randomized allocation or a control group.

The intervention was lisdexamfetamine. The study description says cardiovascular assessment included echocardiography and cardiopulmonary exercise testing. The registered primary outcome was left ventricular size, defined as left ventricular end-diastolic dimension measured by transthoracic echocardiogram. Its stated timeframe was 3-6 months of stimulant medication.

The endpoint population description states that 14 subjects completed the endpoint echocardiogram and that one hypertensive subject missed the scheduled endpoint appointment. The registry lists three outcome measures, but numerical results for the primary measure are not reported in the registry record. It also lists no statistical analyses. The record therefore does not establish how the primary endpoint was summarized or compared, nor whether other measurements were analyzed.

The record gives a completed status and identifies the study as phase 4. It does not report a detailed statistical analysis plan, a sample-size justification, or an interim-analysis plan. The sample-size assumptions associated with the planning illustration describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not evidence that the study itself used a two-arm design: its registered model is single-group. Numerical planning estimates are not reported in the registry record.

Because this was not a randomized comparison, the two blood-pressure subgroups should not be treated as interchangeable treatment and control groups. Differences between them could reflect their clinical characteristics, including hypertension status and antihypertensive treatment, as well as other unreported factors. The registry information does not support attributing subgroup differences to lisdexamfetamine 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 14 subjects completed endpoint TTE; one HTN subject missed the scheduled endpoint TTE appointment.

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 Left Ventricle Size, measured over 3-6 months.

The registered primary endpoint is left ventricular end-diastolic dimension (LVEDD), a measurement of the size of the heart’s left ventricle at the end of filling. The study assessed it by transthoracic echocardiogram, an ultrasound examination of the heart. The stated timeframe is 3-6 months after stimulant medication.

As a continuous measurement in millimeters, LVEDD can describe cardiac chamber size on a numerical scale. In general, an echocardiographic measurement is used to characterize cardiac structure; its interpretation depends on measurement procedures, participant characteristics, and the clinical context. A measurement by itself does not establish why a value is what it is, or whether a change is caused by treatment.

The registry record identifies the planned summary as a mean with standard deviation, but does not report the endpoint’s numerical mean or standard deviation. It also does not report a baseline value, a change from baseline, or a comparison estimate. The record says 14 subjects completed the endpoint echocardiogram and that one hypertensive subject missed the scheduled endpoint appointment. Thus, the endpoint definition and some completion information are available, but the actual endpoint result is not reported in the registry record.

The study description also names blood pressure, heart rate, and in-depth cardiovascular testing as areas of interest. Those descriptions do not substitute for numerical results. Without the endpoint values and a stated analysis, the registry entry cannot show the size or precision of any observed change in LVEDD.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary measure, an endpoint timeframe, and a planned summary as a mean with standard deviation. It does not report an analysis of that endpoint. The statistical concepts below are general explanations; they do not describe methods confirmed as having been used in this study.

What a mean and standard deviation describe

For a continuous measurement such as LVEDD, the mean is the arithmetic average across the participants included in an analysis. The standard deviation describes how dispersed individual measurements are around that average. They answer different questions: the mean describes the center of the observed values, while the standard deviation describes their spread. Neither alone indicates how precisely the mean estimates a broader population value. The registry does not report either endpoint statistic.

What an estimate and confidence interval would add

In general, an estimate gives the size and direction of a quantity of interest, such as an average value or change. A confidence interval expresses the uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but interpretation also depends on the design and what quantity is being estimated. No endpoint estimate or confidence interval is reported in the registry record, so the precision of the primary result cannot be assessed.

Why a comparison group matters

In general, a randomized comparison is designed to make treatment groups comparable, on average, in ways that reduce confounding. This study is registered as single-group, with no randomized comparator. A follow-up measurement in participants receiving treatment can describe their observed outcomes, but does not alone estimate what would have happened without treatment. The normotensive and hypertensive groups are not randomized treatment arms; a difference between them would not have the same interpretation as a randomized treatment contrast.

What the planning assumptions mean

The registry describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a stated fraction of the observed effect. These assumptions describe an illustrative calculation rather than the registered single-group design. The assumptions do not establish the study’s original sample-size rationale, and that rationale is not reported in the registry record. A planning estimate is not an observed result or a measure of achieved power. Numerical estimates from the planning illustration are not reported in the registry record.

In general, a significance level is a threshold used in a specified testing procedure; it does not tell readers the probability that a result is true. A two-sided test allows departures in either direction under its alternative hypothesis. A normal approximation uses properties of the normal distribution to approximate a sampling distribution. Whether that approximation is suitable depends on the data and analysis, details not reported for the endpoint.

What multiplicity and over-dispersion would mean generally

When several outcomes or hypotheses are tested, multiplicity can increase the chance of obtaining at least one apparently notable result by chance. Analysts may use prespecified strategies to address that issue. The registry lists three outcome measures but does not report a multiplicity strategy or statistical analyses. It is therefore not possible to determine whether or how multiple outcomes were handled. Over-dispersion is a general concern for count outcomes when variability exceeds what a chosen model assumes; it is not a reported feature of this continuous primary endpoint, and the registry does not describe count-model analyses.

These general concepts cannot fill the gap in the posted outcome information. The record does not provide an analysis population, an endpoint estimate, an uncertainty interval, a test result, or enough detail to reproduce an analysis. In consequence, the design and outcome definition can be described, but an inferential result for LVEDD cannot be evaluated from the registry record.

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("Normotensive Adults With ADHD", "Primary Hypertensive Adults With ADHD")
n   <- c(7, 7)
m   <- c(44.42, 43.57)
sp  <- c(7.07, 6.13)
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  Normotensive Adults With ADHD  7  44.420  7.070  37.881  50.959
CARM  Primary Hypertensive Adults With ADHD  7  43.570  6.130  37.901  49.239

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but does not report a statistical analysis or a plan for controlling multiplicity. In general, multiplicity arises when several outcomes or hypotheses are examined: interpreting each test independently can make chance findings more likely across the full set. A prespecified adjustment or hierarchy can help clarify which findings are confirmatory and how uncertainty should be interpreted. No such approach is reported in the registry record, so the handling of multiple outcomes is not known.

The primary endpoint description states that 14 subjects completed the endpoint transthoracic echocardiogram, and that one hypertensive subject missed the scheduled endpoint appointment. Enrollment was 24. The record does not explain the disposition of every enrolled participant or identify a complete analysis population for the endpoint. It also does not report whether participants without an endpoint measurement were excluded, whether any values were imputed, or whether another missing-data method was used. These details are not reported in the registry record.

In general, missing outcome data can affect interpretation if the participants with measurements differ from those without measurements. The direction and extent of any effect depend on why measurements are missing and on the assumptions used to address them. The registry information does not establish those reasons or assumptions, so the potential effect of missing endpoint measurements cannot be quantified.

The record also does not report an interim-analysis plan, a statistical analysis plan, or a sample-size justification. The planning assumptions described for an illustration do not establish the study’s original design rationale or analysis procedures. Without reported endpoint results and methods, neither multiplicity handling nor missing-data sensitivity can be assessed.

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 4.2% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events separately for the two participant groups. Among normotensive adults with ADHD, the record lists zero serious adverse events among 14 at risk. Among primary hypertensive adults with ADHD, it lists zero among 8 at risk. These are observed counts in the registered groups; they do not establish that serious events could not occur or compare risk with an untreated group.

The record also lists other adverse events for 11 of 14 normotensive adults and 8 of 8 primary hypertensive adults. The specific event terms are not listed in the registry record, so the types and clinical importance of those events cannot be described from these figures. The entries do not indicate whether a participant had one event or more than one.

Deaths are not reported in the registry record. The available counts should be read as descriptive safety reporting from a small study, not as a precise estimate of event risk or a causal comparison. The groups were not randomized control arms, and the posted figures do not provide a comparator receiving no lisdexamfetamine.

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

The registry record establishes that investigators planned a detailed cardiovascular study of lisdexamfetamine in adults with ADHD, including people described as normotensive and people with primary hypertension receiving stable antihypertensive medication. It identifies echocardiography and cardiopulmonary exercise testing in the study description. The primary measure was LVEDD by transthoracic echocardiogram after 3-6 months of stimulant medication.

The record does not report the numerical result for that primary measure. It therefore does not show the average LVEDD, the variability among participants, or the size and precision of a change. It also does not provide a reported statistical analysis of the primary outcome. The absence of these results cannot be interpreted as a finding of no change; the result is simply not reported in the registry record.

The design does not support a randomized causal comparison. There is no randomized untreated or placebo group in the registered design, and the blood-pressure subgroups are not substitutes for such a group. Observed values during treatment, even if reported, would not by themselves show what would have occurred in the absence of treatment. The record also does not report an analysis comparing the subgroups.

The adverse-event counts describe reported serious and other events in the two groups, but the event terms for the other category are absent. These counts should not be taken as a complete characterization of cardiovascular effects or as a precise estimate of safety. Deaths are not reported in the registry record.

In general, a trial’s design, outcome estimates, and uncertainty all matter when interpreting evidence. Here, the design and endpoint definition are available, but the primary numerical findings and analytic details are not. The study entry can therefore be read as a description of the research question and registered approach, not as a complete report of the endpoint’s observed effect.

14. Why This Trial Matters Statistically

This study is statistically notable because it addresses a clinically relevant measurement using an intensive cardiovascular assessment, while its registered design is a single-group study. That distinction matters: detailed measurements can characterize participants during treatment, but a treatment effect requires a suitable comparison for the counterfactual question of what would have happened otherwise.

The registry distinguishes normotensive adults from adults with primary hypertension receiving stable antihypertensive medication. This is useful context for understanding the population under study, but the groups are not randomized. Statistical comparisons between them, if made, would be vulnerable to differences in clinical characteristics and treatment context. They cannot be interpreted as a randomized estimate of lisdexamfetamine’s effect.

The endpoint is also clearly defined in terms of a cardiac structure measurement and an assessment method. Yet the endpoint estimate, variability, and analysis are not reported in the registry record. That makes the difference between registration detail and results reporting especially important: a reader can identify what investigators intended to measure without being able to quantify what they observed.

The safety entries show why counts need context. Zero serious adverse events are listed in each group, alongside other adverse-event counts, but the record does not list the event terms or provide a randomized comparison. Sparse counts in a limited study do not by themselves establish the absence of risk. The number of participants with a completed endpoint measurement is also reported, while the full missing-data handling is not.

For statistical readers, the central lesson is to separate an endpoint definition, a study design, and an analyzed result. Each answers a different question. This record documents the first two in part, but does not report the numerical primary outcome or its uncertainty. That limits the conclusions that can responsibly be drawn from the posted information.

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 principal limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. Although the outcome definition, unit, summary type, and timeframe are stated, no mean, standard deviation, baseline value, change estimate, or confidence interval is given. No statistical analysis is listed, so the endpoint’s precision cannot be assessed.

The single-group design provides no randomized control comparison. It can describe outcomes among participants receiving lisdexamfetamine if results are reported, but it cannot by itself distinguish treatment-associated change from other influences over time. The two blood-pressure subgroups do not solve this problem because they are not randomized to treatment or control status.

The endpoint population description records 14 completed echocardiograms and one missed appointment in a hypertensive subject, while overall enrollment was 24. The record does not explain the disposition of every participant, identify the endpoint analysis population, or describe missing-data methods. It also does not report whether the missing appointment was the only missing endpoint measurement.

The registry lists three outcome measures but gives no multiplicity plan or statistical analysis plan. The reason for the chosen enrollment, interim analyses, and the original sample-size justification are not reported in the registry record. The separate planning assumptions do not establish that the trial was designed or analyzed as a two-arm comparison.

Safety interpretation is also limited: the specific terms for other adverse events are not listed, and deaths are not reported in the registry record. These reporting gaps prevent a detailed assessment of event types and their context. Taken together, these limitations mean that the study’s question and some design details are identifiable, but its primary numerical findings and several key analytic details are unavailable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cardiovascular Study of Lisdexamfetamine in Healthy and Hypertensive Attention Deficit Hyperactivity Disorder Adults — NCT00753012.
• Registry record last updated 2012-09-24; status last verified 2012-08.
• Results first posted 2012-09-24.
• 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

NCT00753012 is a completed phase 4 study sponsored by Massachusetts General Hospital. It enrolled 24 adults with ADHD and is registered as a single-group study with no masking. Participants received lisdexamfetamine and included normotensive adults and adults with primary hypertension treated with stable antihypertensive medication.

The primary outcome was left ventricular end-diastolic dimension measured by transthoracic echocardiogram after 3-6 months of stimulant medication. The record states that 14 subjects completed the endpoint echocardiogram and that one hypertensive subject missed the scheduled appointment. The numerical primary outcome and statistical analyses are not reported in the registry record.

Serious adverse-event counts are listed as zero among 14 normotensive adults and zero among 8 primary hypertensive adults. Other adverse events are listed for 11 of 14 and 8 of 8, respectively; their specific terms are not listed. Deaths are not reported in the registry record.