Targeting Inflammation to Treat Cardiovascular Aging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeting Inflammation to Treat Cardiovascular Aging (NCT01775865), a randomized phase 2 study. The primary outcome is Carotid-femoral Pulse Wave Velocity (CFPWV).

2. Clinical Question

The TIVA study concerned cardiovascular aging, including aortic stiffness, endothelial dysfunction and diastolic dysfunction. Its registry summary describes chronic low-grade inflammation as a proposed contributor to age-related cardiovascular changes. The clinical question was whether a four-week course of salsalate was associated with a change in carotid-femoral pulse wave velocity (CFPWV), the primary measure of aortic stiffness, compared with placebo.

The active and placebo arms were assigned by randomization. The registry describes the study as triple masked, but does not report which groups of people were masked or how masking was maintained. Participants in the salsalate arm received capsules by mouth twice per day, at a total daily dose of 1.5 g, for 4 weeks. The placebo arm received placebo capsules by mouth twice per day for 4 weeks.

A young control group was also included. Its description specifies no intervention and baseline measurements only. It therefore does not represent a parallel four-week treatment comparison in the same way as the randomized salsalate and placebo arms. The primary endpoint description reports 11 completed participants in the salsalate group and 13 in the placebo group after baseline measurements and dropouts.

The registry record does not report the actual CFPWV change estimates or their uncertainty, so the direction, size and precision of the primary comparison cannot be assessed from these details. The study question can be identified, but its numerical answer is not reported in the registry record.

3. Trial Design

This was a Phase 2, randomized, triple-masked, parallel-group study. The registry lists an enrollment of 59 and records the study as completed. The recorded start was 2012-09, and the primary completion was 2016-02. These dates describe the registry record and do not by themselves establish the duration of participation for any individual.

The two intervention arms were salsalate and placebo. The salsalate description specifies 1.5 g/day, taken by mouth twice per day for 4 weeks; the placebo description specifies capsules taken by mouth twice per day for 4 weeks. The registry also lists a young control group, with no intervention and baseline measurements only. That group should be distinguished from the randomized treatment comparison: its description does not specify follow-up treatment or repeat measurements.

The primary endpoint was change in CFPWV from baseline at 4 weeks. The registry notes 3 dropouts in the salsalate group, leaving 11 completed participants, and 1 dropout in the placebo group, leaving 13 completed participants. The adverse-event record separately lists 14 participants at risk in each of those arms and 17 in the young control group. These different counts refer to different record components and should not be treated as interchangeable analysis denominators.

The registry record does not report eligibility details, the specific roles covered by triple masking, a sample-size justification, or a detailed analysis plan. Nor does the available record describe how the baseline-only control group was used in the analysis. Randomization and masking are stated design features, but the methods used to implement them 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.

Before assignment: A total of 59 participants were consented/enrolled. A total of 13 were excluded or lost to follow up after consent (n=8 did not meet inclusion criteria after screening; n=1 lost to follow up; n=1 time committment; n=1 moved out of state; n=2 other).

Overall Study

Analysis population for the primary outcome, as defined in the registry: After baseline measurements, there were 3 dropouts in salsalate group for a total of 11 completed in salsalate, and 1 dropout in the placebo group for a total of 13 completed in placebo.

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 Carotid-femoral Pulse Wave Velocity (CFPWV), measured over Change in CFPWV from baseline at 4 weeks.

CFPWV is a measure of how quickly a pulse wave travels along the carotid-femoral arterial pathway. In general, pulse-wave velocity is used as an indicator of large-artery stiffness: a faster wave is interpreted as reflecting stiffer arteries. The registry identifies CFPWV as the primary measure of aortic stiffness and specifies the unit as cm/sec.

The endpoint is framed as change from baseline at 4 weeks, rather than as a single measurement at follow-up. In general, assessing change relates the follow-up measurement to the participant’s starting value and targets the alteration over the stated interval. The registry lists the summary parameter as a mean and the dispersion as a standard error. A mean describes the average measured change within a group; a standard error describes the precision of an estimated mean, rather than the spread of individual participant values.

Arterial stiffness is relevant to the study’s stated topic because the registry summary describes stiffening of central arteries as a feature of cardiovascular aging. That rationale does not make CFPWV a direct measure of every cardiovascular function or clinical outcome. It is a physiological endpoint, and its interpretation is limited to the quantity measured and the follow-up interval.

Although the endpoint definition and summary-statistic type are recorded, the actual group means, standard errors and comparison estimate are not reported in the registry record. Consequently, the recorded endpoint alone does not reveal whether the groups differed or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a mean of a continuous endpoint, with standard error as the dispersion statistic. In general, a continuous measure can take a range of values, rather than belonging to a fixed set of categories. A group mean summarizes the average value or change, while the standard error describes the statistical precision of that estimated mean. It is not the same quantity as the variability among individual participants. Because the registry does not report the actual means or standard errors, their magnitudes cannot be discussed.

The endpoint is change in CFPWV from baseline at 4 weeks. In general, an analysis of change compares follow-up measurements with baseline measurements within participants and then summarizes those changes by group. The precise analysis could use different statistical procedures, and the choice can affect how estimates and uncertainty are calculated. The registry record does not report the specific model, any covariate adjustment, or the exact comparison procedure. It would therefore be inappropriate to infer an adjusted or unadjusted analysis from the endpoint description alone.

Randomization is intended, in general, to create treatment groups whose measured and unmeasured characteristics are balanced on average, although chance differences can remain, particularly in small studies. The registry identifies randomized allocation but does not describe the sequence-generation method, allocation concealment, or implementation procedures. Triple masking is also recorded, but the specific masked roles and procedures are not reported in the registry record. The design labels convey important information, but not every operational detail needed to evaluate risk of bias.

A confidence interval, in general, communicates uncertainty around an estimated effect. Its width depends on factors including the amount of information in the data and variability in the outcome. An interval’s interpretation also depends on the statistical model and assumptions. The registry does not report a confidence interval for the primary comparison, so neither the plausible range of effects nor the precision of the estimate can be assessed. A p-value, if available, would not supply the effect size or explain its practical meaning on its own; no primary comparison p-value is reported in the registry record.

The sample-size assumptions recorded for a planning illustration specify a two-sided significance level of 0.05, equal allocation between the two treatment arms and a normal approximation. The illustrated effect is defined as a stated fraction of the observed effect. Such calculations are planning illustrations based on an observed effect, not observed power and not necessarily the assumptions used to design the trial. No resulting sample-size figures or trial-specific sample-size justification are reported in the registry record. The illustration cannot establish what effect size the study was designed to detect.

In general, over-dispersion occurs when outcome variability is greater than a model assumes. If ignored, standard errors may be too small and confidence intervals too narrow, making estimates appear more precise than they are. This issue is most directly relevant to models for counts or other data with variance assumptions; it is not an established problem for the continuous CFPWV endpoint in this record. The registry does not report an over-dispersion assessment, and there is no basis to claim that it arose in this trial.

Missing measurements matter because the primary endpoint requires baseline and follow-up information to calculate change. Dropouts are reported in both randomized arms, but the record does not explain whether endpoint data were available for every completer, why participants withdrew, or how incomplete observations were treated. In general, excluding participants with missing outcomes can change the population represented by the analysis if missingness is related to participant characteristics or outcomes. Alternative approaches require assumptions that should be stated. The analysis method for missing data is not reported in the registry record.

The registry lists three outcome measures, identifies FMD as a secondary outcome and records zero analysis entries. A multiplicity adjustment may be considered in general when several outcomes or comparisons are tested, because repeated testing can increase the chance of a false-positive finding across the set. Whether an adjustment is appropriate depends on the intended inferential claims and analysis plan. The registry does not report a multiplicity strategy, a hierarchy among outcomes, or results for the analyses. The record also does not state whether an interim analysis was planned or conducted.

Finally, the primary endpoint description gives completion counts, while the adverse-event record gives participants at risk. Statistical denominators should always be tied to the outcome and analysis in question. The registry does not provide a complete analysis-population definition, such as whether the primary analysis included all randomized participants or only those with observed follow-up. The design and count information therefore cannot substitute for an analysis specification or numerical result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures overall and identifies brachial artery flow-mediated dilation (FMD) as a secondary outcome. CFPWV is identified as the primary endpoint. The other outcome measures are not reported in the registry record. Although an analysis count of zero is recorded, numerical outcome analyses are not present in the record details. That absence should not be read as evidence that no analyses were performed; it means that analyses are not reported in the registry record.

When multiple outcomes or comparisons are evaluated, general statistical practice distinguishes the primary question from additional questions and considers whether the chance of false-positive findings across tests should be controlled. Approaches may include defining a hierarchy or adjusting significance criteria, but the appropriate approach depends on the analysis plan and intended conclusions. The registry does not report a multiplicity procedure, a testing hierarchy, or whether the listed outcomes were analyzed together.

The endpoint description notes dropouts after baseline: 3 in the salsalate arm and 1 in the placebo arm, with 11 and 13 participants completing, respectively. The record does not report the reasons for dropout, availability of follow-up measurements, or the method used to handle missing values. It also does not define the primary analysis population, specify whether participants were analyzed according to randomized assignment, or describe sensitivity analyses for missing data. These points are important because different analysis populations and missing-data assumptions can lead to different estimates.

The registry record does not report interim analyses, stopping rules, or detailed statistical-analysis methods. These omissions limit assessment of how the analysis was planned and interpreted, but they do not establish that any particular procedure was or was not used.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event record lists 14 participants at risk in the salsalate arm and 14 in the placebo arm, and 17 in the young control group. It records zero serious adverse events in each group and zero deaths in each group. For other adverse events, the record lists 1 affected participant in the salsalate arm, 1 in the placebo arm and 0 in the young control group.

These figures describe the adverse-event entries, not the primary endpoint completion counts. The primary endpoint description separately reports 11 completers in the salsalate group and 13 in the placebo group after dropouts. Different denominators may reflect different record components and should be interpreted in their stated context rather than combined.

In general, an adverse-event count is descriptive. A count of zero recorded serious events does not establish that an intervention has no safety risks, and counts from a small study do not precisely characterize uncommon events. The registry does not list serious-event terms, and the top serious-event terms field is empty. The record also does not provide details about the nature, timing, severity or relationship to treatment of the other adverse events. Accordingly, the safety figures should be read as the events recorded during this study, not as a complete estimate of safety beyond it.

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

The registry record establishes that a randomized, triple-masked, parallel Phase 2 study compared salsalate with placebo over 4 weeks and selected change in CFPWV as its primary endpoint. It also documents a baseline-only young control group, completion counts for the randomized arms, and a small number of recorded other adverse events. These details describe the study’s question and conduct.

They do not provide the numerical primary outcome results. Without group changes, a between-group estimate and its uncertainty, there is no basis in the registry record to characterize the direction or size of the CFPWV comparison. There is also no basis to characterize statistical significance or precision. The endpoint’s rationale and the trial’s design cannot substitute for outcome results.

Even if numerical CFPWV results were available, the endpoint would represent a measure of arterial stiffness over the specified interval, not every aspect of cardiovascular aging or cardiovascular disease. A physiological change does not, by itself, establish a change in symptoms, clinical events or long-term health outcomes. The registry summary describes cardiovascular aging as a broad topic involving vascular and cardiac functions, while CFPWV addresses a particular aspect of that topic.

The recorded completion and safety counts also have limits. Dropouts are noted, but reasons and missing-data handling are not. The safety entries record no serious events and no deaths in the listed groups, but the record does not give detailed event descriptions. Neither feature establishes the absence of risk or resolves uncertainty about outcomes.

Overall, the available information supports a careful description of the trial design and what the registry records, but not a claim that salsalate did or did not change aortic stiffness. Any stronger conclusion would require numerical results and sufficient information about the analysis and missing data.

13. Why This Trial Matters Statistically

This study illustrates why a trial’s design and its results must be read separately. Randomization, masking, a defined treatment period and a specified primary endpoint describe how the investigators framed the comparison. They do not reveal the observed treatment difference. For this record, the endpoint and completion counts are documented, but numerical primary outcome results are not reported in the registry record.

The distinction between an endpoint mean and its standard error is also important. The mean would describe the average change in CFPWV, while the standard error would describe precision of that estimated mean. A treatment comparison and an uncertainty interval would be needed to judge how well the data distinguish the observed difference from other plausible values. Those estimates are not available in the registry information described.

The record further shows why participant counts need context. Enrollment, adverse-event denominators and primary-endpoint completion counts describe different aspects of a study. Treating them as if they were the same analysis population would obscure what information contributes to each result. The dropout information makes the missing-data question relevant, but the approach used to address it is not reported.

Finally, the listed primary and secondary outcomes raise questions about the analysis plan and multiplicity. Statistical interpretation depends not only on which measurements were collected, but also on which comparisons were prespecified and how their uncertainty was handled. The registry does not report those details. These features make the record useful for understanding the study’s structure while underscoring the limits of inference when results and analysis methods are absent.

14. 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 limitation for interpretation is the absence of numerical primary-endpoint results in the registry record. The stated mean and standard error are types of summaries, not values. Without estimates for the randomized arms or their comparison, the primary result cannot be described quantitatively.

The endpoint description reports dropouts and completers, but does not explain the reasons for withdrawal, whether follow-up CFPWV values were available, or how missing data were handled. The primary analysis population and the treatment of participants after randomization are not reported. These gaps prevent assessment of whether the endpoint results, if available elsewhere, would represent all randomized participants or a subset.

The study also included a young control group with baseline measurements only and no intervention. Its purpose in the analysis is not reported. The group should not be assumed to provide a randomized or follow-up comparator for the four-week treatment effect.

Other design and analysis details are not reported in the registry record, including eligibility criteria, masking procedures, the sample-size justification, the statistical model, adjustment for other variables, multiplicity handling and interim analyses. The registry lists three outcome measures but names only the primary endpoint and one secondary outcome in the available details.

Safety information is limited to group counts for serious events, other events and deaths. Serious-event terms are not listed, and descriptions of the other events are absent. These limitations narrow what can be concluded about both the outcome and the safety record; they do not establish that unreported procedures or results did not exist.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Targeting Inflammation to Treat Cardiovascular Aging — NCT01775865.
• Registry record last updated 2018-05-31; status last verified 2018-04.
• Results first posted 2018-05-31.
• 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.

18. Record Summary

NCT01775865, titled Targeting Inflammation to Treat Cardiovascular Aging, is recorded as a completed Phase 2 randomized, triple-masked, parallel study. Enrollment was 59. The intervention arms received salsalate or placebo for 4 weeks; a young control group had no intervention and baseline measurements only.

The primary endpoint was change in carotid-femoral pulse wave velocity from baseline at 4 weeks, summarized as a mean with standard error. Its numerical results are not reported in the registry record. The endpoint description notes 3 dropouts in the salsalate group, with 11 completing, and 1 dropout in placebo, with 13 completing.

The adverse-event record lists no serious adverse events or deaths, and one other adverse-event entry in each randomized arm. The record does not report the detailed analysis plan, missing-data methods, multiplicity strategy or sample-size justification.