EnligHTN IV Trial - Multicenter Sham-controlled RCT of Renal Denervation for Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EnligHTN IV Trial - Multicenter Sham-controlled RCT of Renal Denervation for Hypertension (NCT01903187), a randomized na study. The primary outcome is The Primary Effectiveness Endpoint is the Reduction of Office Systolic Blood Pressure (OSBP) at Six (6) Months Post Randomization Compared to Baseline Between Groups.

2. Clinical Question

That question requires outcome information from both groups at the specified follow-up. The posted primary endpoint data include two participants in the renal denervation group, with a mean of -22.5 mmHg and a standard deviation of 36.0 mmHg. The sham group has no participants contributing a value to this endpoint. Consequently, the record cannot provide the planned between-group comparison at six months.

The registry description says enrollment was terminated early by the sponsor, not because of a safety issue. It also says only two treatment-group randomizations had occurred when enrollment was halted and that sham-group subjects were exited after their one-month follow-up visit. These circumstances leave the primary question unanswered by the posted endpoint results. The record does not establish whether the observed value in the renal denervation group differs from what would have been observed under sham at six months.

3. Trial Design

The EnligHTN IV study is listed as a randomized, parallel-group, single-blind, sham-controlled clinical investigation. Its stated purpose was to demonstrate the safety and effectiveness of the EnligHTN Renal Denervation System for drug-resistant uncontrolled hypertension. Abbott Medical Devices is listed as the sponsor. The study is classified as phase not applicable.

The planned comparison was between renal artery ablation using the EnligHTN system and a sham procedure. The primary endpoint was office systolic blood pressure reduction at six months after randomization compared with baseline. The record lists additional outcomes relating to device- or procedure-related adverse events by severity through six months, major adverse events, specified levels of office systolic blood pressure reduction, and ambulatory blood pressure parameters. Four secondary outcomes are posted, and the record lists six outcome measures overall.

The record gives a start date of 2013-10 and a primary completion date of 2014-06. Enrollment is listed as 4, and the study status is terminated. The primary endpoint description explains that the sponsor ended enrollment early, that this was not related to a safety issue, and that only two treatment-group randomizations had occurred when enrollment was halted. It also states that sham-group subjects were exited after their one-month follow-up visit.

These design details matter because a randomized comparison depends on outcome data from both assigned groups at the endpoint time. Although the study was designed to compare renal denervation with sham, the posted six-month endpoint has no sham observations and only two renal denervation observations. The registry record does not report further details about the randomization procedure, concealment, the blinding procedures, or the intended analysis plan. Those details should not be inferred from the broad design labels.

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.

Procedure

1 Month

3 Month

6 Month

Analysis population for the primary outcome, as defined in the registry: All subjects randomized to the EnligHTN procedure

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: All subjects enrolled.

6. Primary Endpoint

The registry lists the primary outcome as The Primary Effectiveness Endpoint is the Reduction of Office Systolic Blood Pressure (OSBP) at Six (6) Months Post Randomization Compared to Baseline Between Groups, measured over 6 months post randomization.

The primary endpoint is the reduction in office systolic blood pressure, measured in mmHg, at six months after randomization compared with baseline. The registry describes the intended primary effectiveness question as a comparison of this outcome between the renal denervation and sham groups. Office systolic blood pressure is a continuous measure, so the posted endpoint is summarized using a mean and standard deviation.

In general, a baseline-to-follow-up change can describe how a measured quantity differs over time within a group. A randomized comparison between groups is needed to assess whether the observed change differs between assigned interventions; a change in one group alone does not answer that comparative question. This distinction is especially important when the endpoint is framed as a treatment effect rather than simply a within-group observation.

The posted renal denervation result is based on two participants and has a mean of -22.5 mmHg and a standard deviation of 36.0 mmHg. The sham group has zero participants contributing a primary endpoint value. Therefore, the record does not permit a six-month estimate of the between-group contrast. The endpoint is clinically and statistically interpretable as a planned measure, but the available results do not establish the comparative effect of assignment to renal denervation versus sham.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome, reported as a mean and standard deviation. The planned estimand is comparative: the difference in six-month office systolic blood pressure reduction between randomized groups. However, the posted endpoint data contain a value only for the renal denervation group. A two-group comparison requires information from both groups, so no treatment contrast can be estimated from these posted results.

What does a mean describe?

In general, the mean is a measure of the center of a set of numeric observations. Here, the renal denervation group mean is -22.5 mmHg, based on two participants. It summarizes those observed values, but it does not describe every participant’s result, and it does not indicate how much the group mean might vary in a larger study. The registry does not post the individual measurements.

What does the standard deviation describe?

In general, a standard deviation describes how dispersed observations are around their mean. The posted standard deviation is 36.0 mmHg for the two renal denervation observations. It is not a measure of uncertainty in the same sense as a confidence interval, and it does not quantify the uncertainty of a between-group treatment effect. With very few observations, any estimate of variability is particularly unstable. The sham group has no primary endpoint observations, so a standard deviation for that group is also unavailable.

Why is a confidence interval not available?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure and its assumptions. It helps describe precision, but it cannot repair missing outcome information for one group. Since the registry posts no sham endpoint values and no between-group estimate, it provides no confidence interval for the primary comparison. A confidence interval for the renal denervation mean alone would not answer the randomized comparative question, and none is posted.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable in expectation, reducing systematic differences in measured and unmeasured baseline characteristics. That benefit depends on having outcome data that allow the assigned groups to be compared. Randomization by itself does not produce a treatment-effect estimate when one group has no observations for the primary endpoint. The record identifies the study as randomized but does not report the detailed allocation procedure.

How should the planning assumptions be read?

Any sample-size planning illustrations associated with this analysis are scenarios, not observed trial results and not evidence that the study had a particular probability of detecting an effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations refer to participants per arm for a target power level. These assumptions describe a hypothetical planning exercise based on the observed effect; they are not the trial’s own design justification. The registry record does not report the trial’s sample-size justification, and the posted data are too limited to turn a planning illustration into evidence about the study’s achieved power.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that the observed variability is greater than expected under a simple model such as a Poisson model. It can affect standard errors and confidence intervals if the model does not account for that extra variability. The primary endpoint in this record is continuous and is summarized by a mean and standard deviation, so a count-outcome over-dispersion model is not the issue determining whether the primary comparison can be made. The registry record does not report model-based analyses for the primary endpoint.

Why are recalculations limited?

A recalculation from posted summary statistics can only be made when the required quantities are available for the comparison of interest. Here, the sham primary endpoint group has no observations. The record also lists no analyses for the primary comparison. Thus, an unadjusted re-calculation of the two-group endpoint contrast is not possible. If a discrepancy between a sponsor analysis and a simple recalculation were reported, the sponsor’s own analysis would take precedence; the registry entries do not identify such a discrepancy or provide a sponsor estimate for this endpoint.

These methods distinctions separate the observed group summary, uncertainty about an estimate, a randomized contrast, and a hypothetical sample-size scenario. In this trial record, only the first is posted for the primary endpoint. The central limitation is not a choice among statistical models; it is the absence of primary endpoint data from the sham group and the very small number in the renal denervation group.

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("Renal Denervation")
n   <- c(2)
m   <- c(-22.5)
sp  <- c(36)
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  Renal Denervation  2  -22.500  36.000  -345.947  300.947

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan describing how multiple outcomes or multiple tests were handled. It lists a primary effectiveness endpoint and four posted secondary outcomes, including adverse events, major adverse events, specified office systolic blood pressure reductions, and ambulatory blood pressure parameters. Whether the study planned an adjustment for multiplicity, a hierarchy among outcomes, or another procedure is not reported in the registry record.

In general, testing many outcomes can increase the chance of observing a nominally unusual result even when there is no underlying effect. Prespecified outcome order and multiplicity procedures can help interpret a family of tests. They cannot be assumed for this study because the registry record does not report them, and no analyses are posted.

Missing endpoint data are decisive for the primary question. The record reports two renal denervation endpoint observations and zero sham endpoint observations at the six-month primary time point. The registry description says enrollment ended early and sham-group subjects were exited after their one-month follow-up visit. It does not report a missing-data method, an imputation procedure, or a sensitivity analysis for the primary endpoint. There is therefore no basis to reconstruct six-month sham outcomes or to assess how a particular missing-data assumption would affect the comparison.

The registry record also does not report analysis populations, such as whether the primary analysis was intended to include all randomized participants or a defined subset. The small number contributing to the posted endpoint should not be relabeled as an intention-to-treat, per-protocol, or other analysis population without documentation. The absence of reported analytic details is a limitation of what can be concluded from this record, not evidence that any specific procedure was or was not used outside the record.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: subarachnoid haemorrhage (50.0%), acute renal failure (50.0%), bowel obstruction (50.0%), chest pain (50.0%).

The adverse-event summaries list two participants at risk in each group. Serious adverse events affected two participants in the renal denervation group and zero in the sham group. Other adverse events affected two participants in the renal denervation group and zero in the sham group. The record lists zero deaths in both groups.

The registry also lists Subarachnoid Haemorrhage, Acute Renal Failure, Bowel Obstruction, and Chest pain among the top serious adverse-event terms, each with a reported percentage of 50.0%. These entries describe the record’s posted terms and percentages; they should not be treated as a complete event-level account. The registry information does not explain in the registry entries how the percentages were calculated or whether participants could contribute to more than one term.

These figures are descriptive and come from very small groups. They do not provide a stable estimate of the comparative frequency of adverse events. The registry states that early termination was not related to a safety issue, but that statement does not change the need to distinguish the sponsor’s stated reason for stopping enrollment from the adverse-event counts that were posted. Follow-up details beyond the statement that sham subjects exited after one month are not reported in the registry record.

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

The posted results establish that this registry record contains a small amount of outcome information from a trial intended to compare renal denervation with sham. For the primary endpoint, there are two observations in the renal denervation group and none in the sham group. The reported renal denervation mean is -22.5 mmHg, with a standard deviation of 36.0 mmHg. This describes the available group summary; it is not a treatment-effect estimate.

The record does not establish whether renal denervation differs from sham in six-month office systolic blood pressure reduction. No between-group estimate, confidence interval, or primary endpoint analysis is posted. The absence of a comparison is not evidence of no difference, nor does the single-group mean establish a comparative benefit or harm. It means the registry record does not contain the information required to answer the primary question.

The record also does not establish the precision of a comparative effect. General statistical interpretation of precision requires an estimate and its uncertainty, such as a confidence interval. Neither is posted for the primary contrast. The small number of endpoint observations further limits what the group summary can say about a broader population, but the main obstacle is that sham endpoint data are absent.

The adverse-event entries describe events recorded in the small groups and should not be translated into a definitive safety comparison. The record lists serious and other adverse events in the renal denervation group, none in the sham group, and no deaths. Those counts are not sufficient to settle comparative safety, particularly given the limited size and early termination described in the record. The stated reason for stopping enrollment was not related to a safety issue; that is distinct from a conclusion about safety outcomes.

Finally, a planning illustration based on an observed effect, if consulted, is hypothetical rather than a report of what the trial was designed to detect or what its actual power was. The registry record does not report the trial’s sample-size justification or analysis plan. The defensible conclusion is therefore narrow: the record documents the study design, early termination, and limited posted outcome summaries, but does not resolve the intended six-month randomized comparison.

14. Why This Trial Matters Statistically

This trial matters statistically because its intended design and its available results diverge in a way that is easy to overlook. The record describes a randomized, single-blind, sham-controlled comparison, a structure intended to support an intervention-versus-control estimate. Yet the primary endpoint has observations only in the renal denervation group. A familiar design label cannot compensate for the absence of outcome data from a comparator group.

The case illustrates why an arm-level mean is not the same as a treatment effect. A treatment effect for a randomized trial is based on a comparison between assigned groups, while a single-arm summary describes only the observations available in that arm. The posted mean and standard deviation are therefore meaningful as descriptive statistics for the two recorded renal denervation observations, but they do not answer the trial’s primary comparative question.

It also illustrates the importance of reporting the flow of a study and the timing of outcome collection. The registry states that enrollment ended early, gives the sponsor’s stated reason as unrelated to safety, and notes that sham-group subjects were exited after the one-month follow-up visit. That context helps readers understand why a six-month sham endpoint is unavailable, without implying what those missing values would have been.

Finally, sample-size planning scenarios and observed evidence serve different purposes. A planning illustration can describe assumptions under which a future or hypothetical comparison might be sized. It cannot replace the missing comparison or establish the performance of a terminated study. Careful interpretation keeps design intent, observed summaries, safety counts, and hypothetical planning separate.

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 main trial-specific limitation is early termination. The registry lists enrollment as 4 and the study status as terminated. Its primary endpoint description says only two treatment-group randomizations had occurred when enrollment was halted, and that the decision was not related to a safety issue. The record does not give a fuller account of the reasons or process for termination.

The primary endpoint is not available for the sham group at the specified six-month time point. The registry says sham-group subjects were exited after their one-month follow-up visit. As a result, the posted data do not support the intended between-group endpoint comparison. The renal denervation summary is based on two participants, which also means that the reported mean and standard deviation offer very limited descriptive information.

Further details needed to evaluate the conduct and analysis are not reported in the registry record. These include the full eligibility criteria, participant characteristics, detailed randomization and blinding procedures, the sample-size justification, the statistical analysis plan, analysis populations, and missing-data methods. The record also does not post individual participant outcomes, a confidence interval, or an analysis of the primary contrast.

The record lists adverse-event summaries and serious adverse-event terms, but the posted information does not provide enough detail to reconstruct the full event-level experience or compare event rates with precision. The available safety counts should therefore be treated as descriptive. The absence of reported analyses should not be interpreted as proof that none were conducted outside the registry, but those analyses cannot be assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: EnligHTN IV Trial - Multicenter Sham-controlled RCT of Renal Denervation for Hypertension — NCT01903187.
• Registry record last updated 2019-02-15; status last verified 2019-01.
• Results first posted 2016-03-17.
• 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

The EnligHTN IV trial is listed as a randomized, single-blind, parallel-group, sham-controlled investigation of renal denervation for uncontrolled hypertension. The sponsor is Abbott Medical Devices. The registry gives a start date of 2013-10, a primary completion date of 2014-06, enrollment of 4, and terminated status.

The primary endpoint was six-month office systolic blood pressure reduction compared with baseline. The posted renal denervation summary includes two participants, a mean of -22.5 mmHg, and a standard deviation of 36.0 mmHg. No sham participants have a posted primary endpoint value, so the planned between-group comparison is not estimable from these data.

The record lists two participants at risk in each group for adverse-event summaries and zero deaths in both groups. It reports that enrollment was halted early for a reason not related to safety and that sham-group subjects were exited after their one-month follow-up visit. The registry record does not report the primary analysis, its confidence interval, or the trial’s statistical analysis plan.