This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Anxiety-mediated Impairments in Large Elastic Artery Function and the Autonomic Nervous System (NCT03109795), a randomized phase 4 study. The primary outcome is Aortic Stiffness.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03109795 |
| Phase | Phase 4 |
| Condition | Anxiety, Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 35 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Iowa |
| Results posted | Yes |
2. Clinical Question
Population
The intended study population was people with moderate-to-high anxiety. The registry summary describes identifying interested individuals through an online screening survey, with advertisements, flyers, and mass emails directing people to that survey. The registry also mentions baseline measurements in control subjects with low or no anxiety. It does not report how many people were screened, how eligibility was determined in practice, or how many participants completed any study assessment. The primary outcome record states that the study was terminated before any participant was randomized to groups.
Intervention
The intervention was clonidine, described as a short-term blockade of sympathetic nerve activity. The study summary describes a 4 weeks intervention period and intended assessments of anxiety symptoms, vascular function, inflammation, muscle sympathetic nerve activity, and oxidant stress. It does not report that any participant received clonidine.
Comparator
Hydrochlorothiazide was designated as a blood-pressure-lowering control condition. The registry describes it as the comparator for clonidine, not as a no-treatment condition. The record does not report that any participant was randomized to or received hydrochlorothiazide.
Primary question
The primary outcome was aortic stiffness, assessed using the carotid-femoral pulse wave velocity technique, with a timeframe of 4 weeks. The planned clinical question was whether the intervention groups differed on that measure after treatment. Because the study was terminated before randomization, no between-group estimate, confidence interval, or test of that question is reported in the registry record.
3. Trial Design
The registry identifies this as a phase 4, randomized, triple-masked, parallel-group study sponsored by the University of Iowa. The listed enrollment is 35. The interventions were clonidine and hydrochlorothiazide. The study status is terminated. Its start date is 2017-04-10 and its primary completion date is 2023-06-30. These registry fields describe the study design and record status; they do not establish that participants were enrolled into treatment groups or that intervention outcomes were collected.
The summary describes an intended comparison among individuals with moderate-to-high anxiety. People interested in the study were to be identified through an online screening survey. Those considered eligible were to be randomized to clonidine or hydrochlorothiazide. The primary outcome record clarifies that termination occurred before any participant was randomized. Accordingly, the randomized comparison remained unobserved, regardless of the design label in the registry.
The planned intervention period was 4 weeks. For participants already taking blood-pressure-lowering medication, the summary describes a 2 weeks washout before and during the study. During that washout, it planned safety visits, including blood pressure measurements at 4 days and 7 days after washout began. These are descriptions of intended procedures, not evidence that they occurred. Whether any participant entered screening, began a washout, or attended a safety visit is not reported in the registry record.
The summary describes baseline and post-intervention assessments of anxiety symptoms and several physiological measures. It also mentions similar baseline measurements in control subjects with low or no anxiety. The registry does not explain how those control subjects related to the randomized comparison or report their number. Details such as the randomization sequence, allocation concealment, the identities of masked groups, and the specific analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Clonidine | Hydrochlorothiazide |
|---|---|---|
| STARTED | 0 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Study was terminated before any participant was randomized to groups.
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: Study was terminated before any participants were randomized
| Characteristic | Unit | Clonidine | Hydrochlorothiazide | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | |
| Age, Categorical: <=18 years | — | — | — | |
| Age, Categorical: Between 18 and 65 years | — | — | — | |
| Age, Categorical: >=65 years | — | — | — | |
| Sex: Female, Male: Female | — | — | — | |
| Sex: Female, Male: Male | — | — | — | |
| Region of Enrollment: United States | participants | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Aortic Stiffness, measured over 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was aortic stiffness, specified as determined by the carotid-femoral pulse wave velocity technique. The stated timeframe was 4 weeks. This makes the endpoint a measurement of a physiological characteristic rather than a report of a clinical event. The registry summary also describes vascular function assessment using non-invasive, well-established techniques, but it does not provide a detailed measurement protocol for this endpoint.
In general, a trial endpoint should translate its clinical or scientific question into a clearly defined measurement. Aortic stiffness is the named construct in this record, and carotid-femoral pulse wave velocity is the method specified to measure it. Using a defined measure can support a consistent comparison across study groups, provided the protocol, timing, and analysis are applied as planned. The registry record does not report further operational details such as the measurement procedure, repeat measurements, unit, or rules for deriving a participant-level value.
The endpoint's timeframe identifies when the planned assessment was relevant to the intervention; it is not a report that the assessment took place. The primary outcome record states that the study was terminated before any participant was randomized to groups. No endpoint values, group summaries, treatment contrast, or uncertainty estimates are reported. Thus the endpoint is identifiable as a planned outcome, but its observed distribution and its relationship to treatment cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the study was terminated before any participant was randomized to groups. The registry therefore does not report a randomized comparison of clonidine and hydrochlorothiazide. Although the record names a primary endpoint and a 4 weeks timeframe, it contains no group-level aortic stiffness results, no treatment-effect estimate, and no confidence interval or p-value for that endpoint.
The registry lists 35 as enrollment, but that field cannot be read as the number randomized: the primary outcome record explicitly says no participant was randomized. The record does not clarify how the enrollment figure relates to screening, consent, or other activity before randomization. It also lists one outcome measure and zero analyses. Those entries do not supply participant-level observations or an analysis of the intended treatment contrast.
The adverse-event record lists 0 participants at risk and 0 affected for both named intervention groups, with 0 deaths in each. In the context of termination before randomization, these entries do not establish that the interventions were administered without adverse events. They indicate that the registry lists no participants at risk in those groups and no recorded events there; there is no treatment-exposed denominator from which to assess safety.
In general, a confidence interval describes the range of effect estimates compatible with the observed data under the method used. No confidence interval is reported for the primary outcome, because no randomized outcome comparison is reported. Likewise, there is no basis to characterize the observed direction or magnitude of a treatment effect. Any statement that clonidine improved, worsened, or had no effect on aortic stiffness would go beyond the registry record.
The study design describes an intended randomized comparison, but a design label is not an outcome. The planned intervention, comparator, measurement timing, and participant population make the scientific question recognizable; they do not substitute for results. The record supports a description of the planned question and its termination before randomization, not a conclusion about efficacy, equivalence, or comparative safety.
The listed enrollment and the study's termination do not explain why recruitment or randomization did not proceed. The reason for termination, whether recruitment began, and any operational or administrative circumstances are not reported in the registry record. Interpretation should therefore remain limited to the status and outcome information that is recorded, without assigning a cause to the termination.
9. Statistical Methods Explained
The registry labels the design randomized, triple-masked, and parallel. These labels describe the intended structure, but the record does not report that randomization occurred: the primary outcome record says the study ended before any participant was randomized. The following statistical concepts clarify what the planned design would ordinarily mean; they do not describe analyses completed for this study.
What does random allocation contribute?
In general, random allocation assigns eligible participants to study groups through a chance-based process. Its purpose is to reduce systematic differences between groups at the point of allocation, so that a later contrast can be interpreted as an estimate of the intervention effect under the study conditions. Randomization does not guarantee identical groups, and it does not remove all uncertainty. It relies on actual assignment and follow-up data. Here, the record indicates that no participant reached randomized assignment, so there are no randomized groups to compare. The sequence-generation method and allocation concealment procedures are not reported in the registry record.
What does a parallel design mean?
In a parallel-group design, participants assigned to an intervention generally remain in that group while their outcomes are measured over the study period. The registered arms were clonidine and hydrochlorothiazide, with hydrochlorothiazide described as a blood-pressure-lowering control condition. A group comparison would require outcome information for participants in both groups and a defined analysis. Those results are not reported. The record's parallel-design label identifies the intended structure, not completed follow-up or treatment exposure.
What does masking mean?
Masking is intended to limit the influence of knowledge about assigned treatment on participant experience, study conduct, measurement, or analysis. The registry calls this study triple-masked, but does not identify which groups of people were masked or describe how masking was maintained. Because randomization did not occur, the label cannot establish that masking was implemented in practice. No details about unmasking or its handling are reported in the registry record.
How should the endpoint and estimate be understood?
The primary endpoint was aortic stiffness assessed with carotid-femoral pulse wave velocity at 4 weeks. In general, an endpoint is the outcome used to address the research question. A treatment-effect estimate would ordinarily summarize the contrast between outcome values in the randomized groups, using a specified scale and analysis population. A standard error or confidence interval would express uncertainty around that estimate. The record reports none of these quantities for the primary outcome. The measure's unit and dispersion are also not specified.
In general, a p-value evaluates how compatible data are with a specified null model and analysis assumptions; it is not an effect size and does not measure clinical importance. A p-value for this primary comparison is not reported in the registry record. Without the observations and an analysis, neither a statistical test nor an estimate of precision can be interpreted. No recalculated comparison is available from the posted summary statistics.
What do planning calculations represent?
In general, sample-size planning uses assumptions about the effect to detect, outcome variability, allocation, and a chosen significance level and power. The registry describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event illustrations are expressed as participants per arm. Such calculations are planning illustrations, not observed power and not evidence that an effect was found. In this record, no randomized treatment effect is reported to serve as an observed effect for interpretation. The registry does not report the trial's own sample-size justification or establish that these assumptions were used to design the study.
In general, over-dispersion occurs when outcome variability exceeds what a model assumes. If relevant, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for the extra variability. The registry record does not report an outcome distribution, an analysis model, or a finding of over-dispersion for this study. This concept therefore cannot be used to explain any trial estimate.
What can the posted analysis entries establish?
The record lists zero analyses and does not provide a numerical primary outcome result. It also does not report a statistical analysis plan, covariate adjustment, handling of repeated measurements, or a method for missing observations. In general, those choices determine how observations are combined into estimates and how uncertainty is quantified. They cannot be reconstructed from a design label or endpoint description. No claim about a prespecified model, interim analysis, or completed efficacy analysis is supported by the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists aortic stiffness as the primary outcome and also describes intended assessments of anxiety symptoms, vascular function, inflammation, muscle sympathetic nerve activity, and oxidant stress. The record does not report a statistical analysis plan that explains how these outcomes were to be prioritized, whether any were secondary endpoints, or how multiplicity was to be addressed. It also does not report any outcome analyses. Consequently, the registry record does not support an assessment of whether multiple testing adjustments were planned or applied.
In general, multiplicity arises when multiple outcomes, time points, groups, or analyses create multiple opportunities to identify a result that appears notable by chance. A statistical plan can specify which comparisons are confirmatory and how error rates or interpretation will be managed. Those general considerations cannot establish what was planned for this trial. The record notes that the primary outcome was not reduced to one comparison, and it provides no numerical comparison for interpretation.
Missing-data procedures and analysis populations are not reported in the registry record. In general, an analysis population defines which participants and measurements contribute to an estimate, while a missing-data method specifies how absent measurements are handled. These decisions matter because results can depend on who is included and why data are unavailable. Here, termination before randomization means the record does not document randomized participants with primary outcome data. It does not state whether screening or other pre-randomization data exist, nor how such data were handled.
The registry does not report an intention-to-treat population, a per-protocol population, a missingness assessment, imputation, or sensitivity analyses. None should be inferred from the registered design or the absence of reported results. The available record supports only that no participant was randomized and that no outcome analysis is listed.
11. What the Result Does, and Does Not, Mean
The result conveyed by the registry is the absence of a randomized outcome comparison, not a finding that the two interventions were alike or different. The record says the study was terminated before any participant was randomized to groups. It reports no aortic stiffness values, treatment contrast, confidence interval, or p-value. The question the trial intended to answer therefore remains unanswered by the posted results.
This distinction matters because a lack of reported evidence is not evidence of no effect. A study with no randomized participants cannot establish that clonidine has no effect, that hydrochlorothiazide has no effect, or that their effects are equivalent. Equivalence or non-inferiority conclusions require a defined design and an estimate sufficiently precise relative to a prespecified margin; such results and margins are not reported in the registry record. Nor can the intended physiological assessments be treated as evidence of benefit or harm without observed measurements.
The adverse-event entries show 0 participants at risk and 0 affected in each intervention group, and 0 deaths in each. Given the stated absence of randomization, these entries do not show that exposed participants had no adverse events. The record does not provide an exposure denominator or safety follow-up for randomized groups.
In general, confidence intervals help distinguish an imprecise estimate from a precise estimate near no difference. No such interval is reported, so there is no precision estimate to interpret. Likewise, a design's listed enrollment cannot replace actual randomized follow-up, and the listed value of 35 should not be treated as a randomized analysis sample because the outcome record states there were no randomized participants.
The record does establish the intended comparison, the primary endpoint, the stated timeframe, and termination before randomization. It does not establish the reason for termination or the status of any activity before randomization. The appropriate conclusion is limited: the registry documents a planned trial, but does not report results that answer its comparative treatment question.
12. Why This Trial Matters Statistically
This study is statistically notable because its registry design describes a randomized comparison, while the primary outcome record states that termination occurred before any participant was randomized. That difference illustrates a basic distinction in trial interpretation: planned design features define how evidence could have been generated, but only observed randomized data can produce a treatment comparison.
The record names a clinically interpretable physiological endpoint and a defined 4 weeks timeframe. It also identifies a blood-pressure-lowering control condition, rather than presenting the comparison as treatment versus no treatment. Those design details help frame the intended question. They cannot establish whether either intervention changed aortic stiffness, or whether any observed difference would have been precise enough to be informative.
The registry's zero adverse-event entries also illustrate why event counts need denominators and exposure context. With 0 participants listed at risk in each group, the entries should not be interpreted as a safety comparison among treated participants. Statistical summaries are meaningful only in relation to the participants and measurements that generated them.
In general, sound interpretation separates design, conduct, and results. Randomization and masking are design attributes; actual allocation and measurement are matters of conduct; effect estimates and uncertainty are results. The record contains design descriptions but no randomized outcome analysis. Keeping these categories distinct prevents a planned intervention or endpoint from being mistaken for evidence about treatment effects.
The case also underscores that the absence of a reported estimate is different from a null estimate. A null estimate would still be a value calculated from observed data, with uncertainty that could be described. No estimate is reported. Thus the registry supports transparency about the study's status and intended question, while leaving the comparative statistical question unresolved.
13. 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 most consequential trial-specific limitation is that the study was terminated before any participant was randomized. The registry consequently reports no randomized-group outcomes for the primary endpoint. It is not possible to estimate the intervention contrast, assess its precision, or examine whether baseline characteristics were balanced across randomized groups.
The registry lists enrollment as 35, but does not explain how that figure relates to the statement that no participant was randomized. The number screened, eligible, consented, or assessed before termination is not reported in the registry record. The reason for termination and the extent of any pre-randomization study activity are also not reported.
The primary outcome is named and its timeframe is stated, but the record does not report a unit, measurement protocol details, outcome values, dispersion, or analysis method. It does not provide participant-level data or a treatment-effect estimate. The number and status of missing measurements cannot be assessed from the posted results.
The registry identifies the design as triple-masked but does not specify who was masked or how masking was implemented. It does not report the randomization method, allocation concealment, an analysis plan, or the intended analysis populations. These omissions prevent evaluation of several planned safeguards and analytic choices, though they do not change the record's explicit statement that randomization did not occur.
The adverse-event entries list no participants at risk in either intervention group. They therefore do not provide an evaluable safety experience among randomized or treated participants. Finally, while the summary describes several intended physiological and symptom assessments, their results and their relation to the primary endpoint are not reported in the registry record.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Anxiety-mediated Impairments in Large Elastic Artery Function and the Autonomic Nervous System — NCT03109795.
- Registry record last updated 2024-07-29; status last verified 2024-06.
- Results first posted 2024-07-29.
- 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.
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17. Record Summary
The registry record describes a phase 4, randomized, triple-masked, parallel study sponsored by the University of Iowa, with listed enrollment of 35. It compares clonidine with hydrochlorothiazide, described as a blood-pressure-lowering control condition. The intended population was people with moderate-to-high anxiety, and the primary endpoint was aortic stiffness measured by carotid-femoral pulse wave velocity at 4 weeks.
The study status is terminated. The primary outcome record states that termination occurred before any participant was randomized to groups. The registry lists zero analyses and reports no numerical primary outcome comparison. Adverse-event records list 0 participants at risk and 0 affected in each group, with 0 deaths in each; these entries do not describe safety among exposed randomized participants.
The registry therefore records the intended clinical and statistical question but does not provide randomized results to answer it. The reason for termination and the extent of any pre-randomization activity are not reported in the registry record.