A Nurse-led Intervention to Extend the Veteran HIV Treatment Cascade for Cardiovascular Disease Prevention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Nurse-led Intervention to Extend the Veteran HIV Treatment Cascade for Cardiovascular Disease Prevention (NCT04545489), a randomized na study. The primary outcome is Mean Systolic Blood Pressure.

2. Clinical Question

3. Trial Design

The registry describes a randomized, unmasked, parallel-group trial, with an enrollment of 305. Its status is completed. The recorded study start is 2020-12-01, and the primary completion date is 2024-10-01. The phase is listed as NA. The sponsor is the VA Office of Research and Development.

Participants were assigned to either an intervention group or an education control group. The intervention involved 4 visits over 12 months plus focused communication from a nurse or pharmacist, blood pressure monitoring support, and medication management. The education control group also had 4 visits over 12 months and received materials about cardiovascular disease risk reduction. The registry does not report the sequence-generation method, allocation concealment, or other implementation details for randomization.

The primary outcome description defines mean blood pressure as the average of 3 blood pressure measurements collected during an assessment at interviews. The posted primary result is specifically for baseline, among randomized participants who completed the baseline assessment. The reported baseline sample sizes are 152 in the intervention group and 149 in the education control group.

The stated study objective and hypothesis concern blood pressure treatment and a systolic blood pressure reduction over 12 months. Yet the posted primary result is a baseline group comparison, not a follow-up result or a change-from-baseline analysis. The registry record does not report a primary outcome result at 12 months. It also does not report the trial’s original sample-size justification or the details of the planned statistical analysis.

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: While 305 participants were consented and randomized to an arm, 4 withdrew and did not complete the baseline assessment. 301 is the number that completed baseline assessment and will therefore be used as the baseline analytic population for the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The randomized participants who completed the baseline assessment

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 Mean Systolic Blood Pressure, measured over Baseline.

The primary endpoint listed in the registry is mean systolic blood pressure, measured in mmHg. For each participant, the registry describes the measure as the average of 3 blood pressure readings collected during an outcome assessment at an interview. The posted time point is baseline, and the stated population is randomized participants who completed the baseline assessment.

Systolic blood pressure is the upper value in a blood pressure reading and is used in this trial as a continuous measure of cardiovascular risk management. In general, averaging repeated readings can reduce the influence of short-term measurement variation compared with relying on a single reading. That is a general measurement principle; the registry does not give further details about the measurement device, setting, assessor training, or the interval between readings.

The distinction between the intended clinical question and the posted endpoint is important. The trial description states a hypothesis about a reduction over 12 months, but the posted primary measure is baseline mean systolic blood pressure. A baseline comparison can describe the groups’ starting values; it cannot establish whether blood pressure changed during follow-up or whether the groups differed in change. A 12-month result or an explicitly defined longitudinal comparison is not reported in the registry record.

7. Results Posted in the Registry

• Intervention Group: mean 134.60 versus 133.30 on control; difference 1.30 (95% CI -2.41 to 5.01), standardized effect d = 0.08; z-test p = 0.492.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Non-HDL Cholesterol

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Intervention Group: mean 118.00 versus 120.90 on control; difference -2.90 (95% CI -12.08 to 6.28), standardized effect d = -0.07; z-test p = 0.536.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intervention Group and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists Non-HDL Cholesterol repeatedly among its secondary outcomes and includes a detailed baseline comparison for that measure. The posted secondary result concerns baseline values, rather than a change during follow-up. The registry does not report outcome analyses for the other repeated entries, and the reported analyses list contains no entries.

The secondary baseline comparison has a mean difference of -2.9 mg/dL, a confidence interval from -12.08 to 6.278 mg/dL, and an unadjusted p-value of 0.536. Those results do not provide follow-up evidence about the primary blood pressure question. In particular, a secondary measure recorded at baseline cannot establish whether the intervention changed that measure over time or whether changes differed between groups.

Across the outcome information available in the registry, the key pattern is that the posted detailed comparisons are baseline summaries. This means they describe starting measurements, not the intervention’s effects during the planned 12-month period. The registry record does not report a follow-up result that would allow the secondary outcome to corroborate or qualify a longitudinal primary finding.

Unadjusted secondary results carry less weight because they may be among multiple outcomes or comparisons, and no multiplicity procedure is reported. In general, examining many outcomes can increase the chance that at least one result appears notable by chance. Without a reported plan for which comparisons were primary, how multiplicity was handled, or which analyses were prespecified, an individual secondary p-value should be interpreted cautiously. This is a general statistical concern; the registry does not establish that a particular multiplicity problem occurred.

The repeated outcome labels do not establish that four distinct secondary measures were analyzed. Their detailed analyses and any prespecified hierarchy are not reported in the registry record. Accordingly, the secondary information should be treated as limited descriptive evidence rather than as a collection of independent tests that resolves the trial’s main 12-month question.

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

• Non-HDL Cholesterol
• Non-HDL Cholesterol
• Non-HDL Cholesterol
• Non-HDL Cholesterol

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports continuous outcomes as means with standard deviations and gives a mean difference for the primary baseline comparison. In general, a mean is the arithmetic average of observed measurements. A standard deviation describes how dispersed individual measurements are around that average; it is not the same as the uncertainty in the estimated mean. These are descriptive summaries of the observed baseline measurements.

What does the mean difference describe?

The primary comparison is defined as the intervention group minus the education control group. The group means are 134.6 mmHg and 133.3 mmHg, respectively, and the reported mean difference is 1.3 mmHg. This is an unadjusted difference between the posted baseline means. It is not a difference in change over time, and it is not an adjusted estimate from a model. The registry does not report an adjusted primary analysis.

In general, a group difference is interpretable only in relation to the measurement time, population, and analysis used. Here, the measurement time is baseline, and the outcome population is randomized participants who completed baseline assessment. The registry does not establish in the posted result how missing baseline measurements were handled beyond that population description.

How should the standard deviations and standard errors be understood?

The primary group standard deviations are 17.3 mmHg in the intervention group and 15.5 mmHg in the control group. They describe the spread of individual blood pressure measurements within each group. The registry also lists standard errors of 1.403 and 1.27 for the two group means. In general, a standard error expresses the sampling uncertainty of an estimate, while a standard deviation describes variation among observations. The registry does not provide additional detail about how those standard errors were derived.

For the baseline non-HDL cholesterol outcome, the group means are 118.0 mg/dL and 120.9 mg/dL, and the group standard deviations are 42.6 mg/dL and 38.3 mg/dL. Its comparison also includes standard errors. These descriptions concern the baseline data, not changes after the intervention.

What does a confidence interval add?

The primary mean difference has a 95% confidence interval from -2.409 to 5.009 mmHg. In general, a confidence interval gives a range of values compatible with the observed data under the method’s assumptions and conveys uncertainty in the estimate. It is not a guarantee that the true value lies in the interval, and it does not incorporate every source of uncertainty, such as unreported measurement or analysis choices. Because this interval includes zero, the posted baseline comparison is compatible with no group difference as well as with differences in either direction.

The non-HDL cholesterol confidence interval is from -12.08 to 6.278 mg/dL. It also includes zero. In general, the sign of a mean difference depends on the specified subtraction order; the registry’s comparison is intervention minus control. Interpreting a direction therefore requires checking both the sign convention and which outcome and time point are being compared.

What does the p-value say?

The primary unadjusted p-value is 0.492, and the secondary non-HDL cholesterol unadjusted p-value is 0.536. In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions held. It is not the probability that the null model is true, and it does not express the size or practical importance of a difference. These are labeled unadjusted; the registry does not report a multiplicity adjustment for the outcomes or comparisons.

The word unadjusted also matters because the registry does not report a model accounting for covariates or a pre-specified analysis plan for the posted comparisons. The displayed calculations are simple comparisons of the posted summary statistics, not a substitute for a sponsor-reported analysis. The registry’s reported analyses field contains no entries. It does not report whether other analyses were conducted or how they were specified.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means that observed variation is greater than expected under a simple model such as a Poisson model. In general, ignoring over-dispersion can make standard errors too small and confidence intervals too narrow. This trial’s posted primary endpoint is continuous, not a count outcome, and the registry does not report a count-model analysis. The concept is included as general statistical context rather than as a feature established for the posted primary result.

How should the planning illustration be read?

The planning display uses the observed mean difference as a reference and considers fractions of that effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The figures are participants per arm for 80% power and participants per arm for 90% power. The display is an illustration based on the observed effect, not the trial’s original design calculation. In general, smaller effects require more participants to reach the same target power under otherwise similar assumptions. These values are planning quantities, not observed results or evidence about the power achieved by the completed trial.

11. Confidence Intervals and Precision

The principal precision measure for the baseline systolic blood pressure comparison is the 95% confidence interval, from -2.409 to 5.009 mmHg, around the mean difference of 1.3 mmHg. It conveys uncertainty in the estimated baseline difference under the calculation’s assumptions. It includes zero, so the posted data are compatible with no baseline difference and with differences in either direction within the interval.

In general, interval width reflects both the amount of information in the data and the variability of the measure. The primary groups have standard deviations of 17.3 and 15.5 mmHg, and the baseline sample sizes are 152 and 149. The confidence interval should not be read as a range of individual participants’ blood pressure values; the standard deviations describe individual-level spread, while the interval concerns uncertainty in the group difference.

The unadjusted p-value of 0.492 is another description of the baseline comparison under a null model, but it does not convey the magnitude or precision as directly as the interval. A p-value alone cannot show which values remain compatible with the data. Nor does a confidence interval resolve whether a difference would be clinically meaningful; that requires context beyond the interval itself.

Most importantly, precision around a baseline difference is not precision around a 12-month treatment effect. The registry does not report a confidence interval for follow-up systolic blood pressure or for change from baseline. Thus, the interval characterizes only the posted baseline comparison, not the stated longitudinal treatment question.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size display gives participants per arm, not total events. It is a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a study designed, under those assumptions, to have an 80% chance of detecting the specified effect if that effect is the true one. The 90% power column uses a higher target chance of detection and therefore requires more participants per arm in the listed planning scenarios. These are target operating characteristics for hypothetical planning, not descriptions of what happened in the completed trial.

The rows correspond to planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For example, planning for 100% of the observed effect gives 2,509 participants per arm for 80% power and 3,359 participants per arm for 90% power. Planning for 75% gives 4,460 and 5,971 participants per arm, respectively, while planning for 50% gives 10,035 and 13,433 participants per arm. Smaller effects need more participants to be detected with the same target power under the stated assumptions.

This is not observed power. It is a planning illustration derived from the observed effect, and it should not be used as a retrospective measure of the trial’s success or failure. The registry does not report whether these assumptions were used when the trial was designed.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1.300; pooled standard deviation σ = 16.434.
2. n = 2 × (1.96 + 0.842)² × 16.434² / 1.300² = 2,508.5, rounded up to 2,509 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 1.29999999999998                      # observed difference in means
sigma <- 16.4336906168691                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4545489)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,509 (80% power), 3,359 (90% power)
 75% of observed effect: n per arm = 4,460 (80% power), 5,971 (90% power)
 50% of observed effect: n per arm = 10,035 (80% power), 13,433 (90% power)
power.t.test: 2509.5 
Simulated power at n = 2,509 per arm: 0.803 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists secondary outcome entries, but it does not report a multiplicity strategy. It is therefore not reported in the registry record whether the investigators adjusted significance thresholds, controlled a family-wise error rate, used a false-discovery procedure, or specified a hierarchy among outcomes. The posted comparison p-values are unadjusted.

Multiplicity matters in general when several outcomes, time points, or analyses are examined. If each is assessed separately, the chance of observing at least one apparently unusual result can increase. That general concern does not prove that any reported result is spurious. It means that the results are more interpretable when a protocol or analysis plan explains which hypotheses were primary and how secondary comparisons were to be handled. Such details are not reported in the registry record.

Missing-data handling is also not reported. The primary outcome population is described as randomized participants who completed the baseline assessment, and the arm summaries include 152 and 149 participants. The registry does not state whether any randomized participants lacked a baseline assessment, how missing measurements were handled, or whether imputation or sensitivity analyses were used. It also does not report participant flow through the 12-month follow-up.

The record does not specify whether the primary analysis followed an intention-to-treat principle, a per-protocol approach, or another analysis population. The stated baseline population description should not be treated as evidence for any of those approaches. Nor does the record describe adherence, crossover, or how participants with incomplete follow-up would enter a longitudinal analysis.

The registry lists 8 outcome measures and no reported analyses. It does not provide a statistical analysis plan, details of interim analyses, or the original sample-size justification. These omissions limit the ability to assess whether the posted results correspond to prespecified analyses and whether all planned analyses are represented. They are reporting limitations; they do not by themselves indicate that an analysis was or was not conducted.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: congestive heart failure exacerbation (2.0%), death (2.0%), gastroenteritis (1.3%), chest pain hospitalization (1.3%), elective surgery (1.3%).

The registry lists serious adverse event figures for 152 participants at risk in the intervention group and 149 in the education control group. The serious adverse event affected column contains 18 for the intervention group and 16 for the education control group. Deaths are listed separately as 3 and 1, respectively. The other adverse event affected column is 0 in both groups.

The registry also lists serious event terms with percentages, including Congestive Heart Failure Exacerbation and Death at 2.0% each, and Gastroenteritis, Chest pain hospitalization, Elective surgery, and Upper respiratory infection at 1.3% each. These terms and percentages are reported as registry entries; they should not be interpreted as comparative rates calculated from the group totals.

In general, safety counts describe events reported during the study and do not establish that an event was caused by an intervention. The registry record does not provide attribution details, a comparative safety analysis, or further information about event timing and recurrence. The figures are therefore descriptive, not evidence of a causal safety difference between groups.

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

The posted primary result means that the registry reports baseline systolic blood pressure averages of 134.6 mmHg in the intervention group and 133.3 mmHg in the education control group, with an unadjusted mean difference of 1.3 mmHg. Its 95% confidence interval runs from -2.409 to 5.009 mmHg, and the unadjusted p-value is 0.492. These statistics characterize the starting measurements included in the registry record.

They do not show how systolic blood pressure changed over 12 months. They do not estimate a between-group difference in change, and they do not establish whether the intervention achieved the stated reduction hypothesis. The registry’s primary outcome timeframe is baseline, despite the trial description’s focus on a 12-month intervention. A follow-up result or longitudinal analysis is not reported in the registry record.

The interval’s inclusion of zero means that the baseline comparison is compatible with no difference under the analysis assumptions, as well as with values on either side of zero. It does not mean that the groups are proven equivalent. In general, demonstrating equivalence requires an appropriate design and prespecified margin; neither is reported for this comparison. Likewise, the p-value does not tell the probability that the intervention is ineffective or effective.

The record also does not establish that every randomized participant contributed outcome data at follow-up, how missing data were handled, or whether the posted comparisons were prespecified. These uncertainties limit the interpretation of the available results. The baseline summaries can describe the enrolled groups at that time point, but they cannot answer a question about post-assignment effects.

The serious adverse event counts and deaths are also descriptive. Without attribution and comparative analyses, they do not establish causation or a difference in safety. Overall, the registry record provides information about trial design, baseline measurements, and recorded safety figures, but the posted results do not resolve the stated 12-month clinical question.

17. Why This Trial Matters Statistically

This trial is statistically notable because its registry description frames a longitudinal treatment question, while its posted primary result is a baseline comparison. That distinction is central to interpreting clinical trial evidence: a baseline measurement describes where groups started, whereas a treatment-effect analysis needs an outcome after assignment or a comparison of change over time. The reported mean difference and confidence interval are not substitutes for that follow-up estimate.

The trial is described as randomized and parallel-group, with an intended intervention period of 12 months and an education control condition. Those design features provide a framework for comparing groups, but a design description alone does not supply a treatment-effect result. The record’s completed status likewise does not mean that all planned outcomes or analyses are posted in the registry.

The entry is also a useful example of why statistical interpretation must combine effect estimates, uncertainty, measurement timing, and analysis population. The baseline confidence interval gives information about precision for a baseline difference, but it cannot be transferred to a follow-up effect. The unadjusted p-value does not answer the clinical question or quantify practical importance.

Finally, the registry lacks details about the original sample-size justification, missing-data methods, multiplicity handling, and reported analyses. These gaps constrain reproducibility and make it difficult to determine how closely the posted information reflects the original analysis plan. The planning illustration can help explain how target sample size depends on a chosen effect and power, but it does not document the trial’s design assumptions. The statistical importance of the record lies as much in these distinctions and reporting limits as in the baseline numbers themselves.

18. Limitations

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

A central limitation is the mismatch between the stated 12-month blood pressure hypothesis and the posted primary outcome timeframe of baseline. The available primary comparison therefore cannot estimate an intervention effect over the treatment period. A 12-month result, a change-from-baseline comparison, and a longitudinal analysis are not reported in the registry record.

The registry describes the primary population as randomized participants who completed the baseline assessment, but it does not report participant flow, missing measurements, or follow-up completion. The analysis population used for any later outcome is not reported. It is also not reported whether the primary analysis was adjusted, what covariates might have been considered, or whether the posted comparison was prespecified.

The record does not provide the randomization method, allocation concealment details, protocol deviations, adherence information, or measurement procedures beyond averaging 3 blood pressure readings collected during interviews. These details would help readers assess implementation and potential sources of bias, but their absence from the registry entry does not establish that the procedures were inadequate.

Outcome reporting is limited. The registry lists Non-HDL Cholesterol repeatedly as a secondary outcome and provides a detailed baseline comparison, while other secondary analyses are not reported. Multiplicity handling and the analysis plan are not reported. The record also does not state the original sample-size justification or interim analysis plans.

Safety information is presented as descriptive counts and terms. Attribution, event timing, and a formal comparison are not reported. These limitations mean the posted record supports a narrow reading of baseline and safety summaries, rather than a complete assessment of 12-month effectiveness or comparative safety.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Nurse-led Intervention to Extend the Veteran HIV Treatment Cascade for Cardiovascular Disease Prevention — NCT04545489.
• Registry record last updated 2025-10-30; status last verified 2025-10.
• Results first posted 2025-10-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry record describes NCT04545489, a completed, randomized, unmasked, parallel-group trial sponsored by the VA Office of Research and Development. It lists enrollment of 305 and compares a nurse-led intervention with an education control condition. The intervention included 4 visits over 12 months, focused communication, blood pressure monitoring support, and medication management; the control group received 4 visits and cardiovascular risk reduction materials.

The posted primary outcome is baseline mean systolic blood pressure among randomized participants who completed baseline assessment. The intervention and control means are 134.6 mmHg and 133.3 mmHg, with a mean difference of 1.3 mmHg, a 95% confidence interval from -2.409 to 5.009 mmHg, and an unadjusted p-value of 0.492. This is a baseline comparison, not a 12-month treatment-effect estimate.

The registry also includes a baseline non-HDL cholesterol comparison and descriptive adverse-event counts. Follow-up outcome results, the original sample-size justification, missing-data methods, multiplicity handling, and a detailed statistical analysis plan are not reported in the registry record.