RENABLATE Feasibility Study CS156 (EC12-02) Study of Catheter Based Renal Denervation to Treat Resistant Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RENABLATE Feasibility Study CS156 (EC12-02) Study of Catheter Based Renal Denervation to Treat Resistant Hypertension (NCT01756300), a na phase 1 study. The primary outcome is The Incidence of Major Cardiovascular and/or Renal Adverse Events Related to the Renal Denervation Procedure That Occurred Within 30 Days Post-procedure..

2. Clinical Question

The study also lists secondary outcomes concerning adverse cardiovascular and renal events through 12 months, office blood pressure, ambulatory blood pressure, reaching a target systolic blood pressure, and systolic blood pressure reduction from baseline. These outcomes cover safety and changes in blood pressure over follow-up. The primary question is narrower: it concerns procedure-related major events within the stated 30-day period. The longer-term secondary outcomes address different timeframes and measures, and should not be treated as substitutes for the primary endpoint.

The central statistical question is descriptive: what event experience was recorded among participants who received the device, and how much uncertainty surrounds that estimate? Because there is no randomized control group, the study cannot establish how the observed event experience or blood pressure changes compare with what would have occurred without the device. The registry record does not report an estimate or uncertainty interval for the primary endpoint, so its magnitude and precision cannot be assessed from the posted results.

3. Trial Design

RENABLATE is described as a prospective, multi-center, non-randomized feasibility study of catheter-based renal denervation for resistant hypertension. The record lists the study as Phase 1 and completed, with an enrollment of 35. Its single-group model means the enrolled participants received the device intervention without a randomized control arm. Allocation is listed as not applicable, and masking is listed as none.

The device intervention was Celsius® ThermoCool® RD, described as an investigational multi-electrode ablation catheter with an integrated ablation system. The study aim was to evaluate safety and effectiveness. The registry record does not report further procedural details, a control treatment, or a protocol for attributing observed changes to the device beyond the endpoint definition.

The primary safety endpoint concerns major cardiovascular and/or renal adverse events related to the renal denervation procedure within 30 days post-procedure. The stated safety analysis population consists of all enrolled subjects who underwent insertion of the study ablation catheter. Other listed outcomes include adverse cardiovascular and renal events through 12 months; actual and change in office systolic and diastolic blood pressure at follow-up; actual and change in 24-hour ambulatory blood pressure at follow-up; reaching target systolic blood pressure; and achieving at least 10 mmHg systolic blood pressure reduction from baseline.

The study start is recorded as 2012-12, and primary completion as 2013-11. The registry record does not report the actual timing of individual participants’ assessments, the number completing each follow-up, or any departures from the planned follow-up schedule. It also does not report a sample-size justification or explain how the enrollment target was selected.

This design can describe events and measurements among the studied participants. Without randomization and a control group, it does not provide a direct estimate of the difference that would arise between device treatment and an alternative. The non-masked design also means the record does not describe masking intended to limit expectations in measurement or reporting. These features are important when interpreting blood pressure outcomes and safety observations, especially when the outcome requires judgment about whether an event is related to the procedure.

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: After signing the inform of consent, subjects were evaluated on inclusion/exclusion criteria, anatomic eligibility, compliant with completing the subject diary. Thirty-three subjects failed and never underwent insertion of the study ablation catheter.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis population, which consists of all enrolled subjects who have undergone insertion of the study ablation catheter.

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 treated subjects who underwent the renal sympathetic denervation procedure.

6. Primary Endpoint

The registry lists the primary outcome as The Incidence of Major Cardiovascular and/or Renal Adverse Events Related to the Renal Denervation Procedure That Occurred Within 30 Days Post-procedure., measured over 30 days post-procedure.

The primary endpoint measures the percentage of participants with a major cardiovascular and/or renal adverse event related to the renal denervation procedure within 30 days post-procedure. The registry lists the endpoint unit as percentage of participants and its parameter as NUMBER. The stated safety analysis population includes enrolled subjects who underwent insertion of the study ablation catheter.

The event definition combines several serious outcomes. These include acute myocardial infarction; specified causes of death; new-onset heart failure; stroke; aortic or lower limb revascularization; lower limb amputation; beginning dialysis; hospital admission for hypertensive emergency unrelated to non-adherence or non-persistence with drugs at each follow-up visit; and hospitalization for atrial fibrillation. The record describes the endpoint as procedure-related, so event occurrence and the attribution of an event to the procedure are both part of its meaning.

In general, a safety endpoint of this kind is used to capture clinically serious events rather than relying only on a change in a measurement such as blood pressure. Combining several event types can make a broad safety question possible, but it also means that the overall result would not identify the frequency of each component unless component results are reported separately. The registry record does not report the primary endpoint result or component-specific results. It therefore does not establish how many participants met this endpoint, which components occurred, or how precise an estimate would be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It describes a single-group study and defines outcomes, but it lists no statistical analyses. The record does not report a test, model, confidence interval, p-value, or adjustment strategy for the primary endpoint. The distinction between a defined outcome and an analyzed result is important: an endpoint description tells readers what was intended to be measured, but it does not reveal the observed estimate.

What does a percentage of participants mean?

For a binary outcome, each participant is classified according to whether the event occurred during the specified period. A percentage of participants expresses the number meeting that definition relative to the relevant analysis population. For this primary endpoint, the registry defines the population as enrolled subjects who underwent insertion of the study ablation catheter, and the event window as 30 days post-procedure. The posted results do not report the number meeting the endpoint or the resulting percentage.

In general, a percentage is an estimate based on the observed participants, not a guarantee that the same percentage would be seen in another group of similar participants. Its precision depends in part on how many participants contribute information and how many events are observed. A confidence interval is one way to express this uncertainty. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed.

Why does the single-group design matter?

The study is listed as non-randomized and single-group, with no masking. It therefore reports no randomized comparison against an alternative intervention or usual care. In general, random allocation can help make groups comparable on measured and unmeasured characteristics, while a control group can provide a reference for changes that might otherwise occur over time. Without that comparison, observed changes among treated participants cannot be attributed to the device alone.

This is relevant to both safety and blood pressure outcomes. A serious event occurring after a procedure is not automatically caused by that procedure. The primary endpoint specifically calls for events related to renal denervation, while the adverse-event summary provides broader event counts. The registry record does not report the adjudication process or how causal attribution was determined. For blood pressure, a change between baseline and follow-up may reflect the intervention, other care, measurement variability, or other factors. The single-group design does not separate these possibilities.

What does the endpoint definition contribute?

The primary endpoint uses a composite definition covering cardiovascular and renal events, with a stated procedure-related requirement and a defined post-procedure timeframe. In general, a composite endpoint can capture several types of clinically serious outcomes within one summary measure. Its overall percentage, if reported, would not by itself show which component drove the result. Component-level counts and definitions are needed to understand the composition of a composite. The registry record does not report the primary endpoint result or component-specific findings.

The secondary outcomes use distinct measures and timeframes. Office blood pressure and 24-hour ambulatory blood pressure are different measurement settings; actual values and changes from baseline answer different descriptive questions. Target achievement and a reduction of at least 10 mmHg are threshold-based outcomes. In general, threshold outcomes classify participants according to whether a chosen cutoff is reached, while continuous measurements retain more detail about the observed values. The record lists these outcome domains but does not report the associated estimates.

What can planning calculations tell readers?

The record includes assumptions for a planning illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. It also specifies that time-to-event planning uses a total event count, while other planning outputs use participants per arm. These are assumptions for an illustration, not evidence that the trial itself used those design choices. In particular, the study is single-group, so a hypothetical two-arm calculation should not be mistaken for the actual trial design.

In general, sample-size calculations estimate how much information might be needed for a planned comparison under specified assumptions. They are not observed results and do not show the probability that a completed study has established an effect. The record does not report a trial-specific sample-size justification, and no numerical planning estimates are reported in the registry record. No claim about observed power can be made from the enrollment count.

What remains unavailable?

The registry record lists no statistical analyses and does not report how missing measurements were handled, how repeated assessments were modeled, or whether any analysis adjusted for other variables. It does not report whether estimates were accompanied by uncertainty intervals or how multiple outcomes were addressed. These omissions prevent assessment of the analysis implementation, not merely the magnitude of a particular estimate. The outcome definitions and study design can be described, but they do not fill in the missing analysis choices or results.

In general, over-dispersion matters when observed variability exceeds what a statistical model assumes; accounting for it can affect uncertainty estimates. There is no reported model or dispersion assessment for this study, so over-dispersion is not an identified issue in the posted analysis. More broadly, the appropriate method depends on the outcome, design, data completeness, and analysis objective. Since the registry record does not report an analysis plan or results, readers should not infer a particular method from the outcome labels alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Renal Sympathetic Denervation")
n      <- c(35)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Renal Sympathetic Denervation  35  0  0.0  0.0  10.0  0.0  9.9  0.1  9.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including the primary safety endpoint and secondary outcomes concerning events and blood pressure at follow-up. It does not report how the study handled the possibility of multiple statistical comparisons. No multiplicity adjustment, hierarchy among secondary outcomes, or distinction between confirmatory and exploratory analyses is reported in the registry record.

In general, testing many outcomes or time points can increase the chance that at least one result appears unusual by chance. A prespecified testing strategy can clarify which comparisons are central and how evidence across multiple outcomes should be interpreted. The listed outcome definitions do not establish what strategy was used, and the record lists no statistical analyses. It is therefore not possible to determine whether any multiplicity procedure was used.

Missing-data methods are also not reported in the registry record. The listed secondary outcomes involve measurements at several follow-up visits, but the record does not state how many observations were available at each visit, how incomplete follow-up was handled, or whether any imputation or other method was used. The number enrolled alone does not establish how many contributed to each outcome assessment.

The primary endpoint population is defined as all enrolled subjects who underwent insertion of the study ablation catheter. The record does not report the number in that population or explain how endpoint status was determined for participants whose information may have been incomplete. Analysis populations for the secondary outcomes are not reported in the registry record.

These are reporting gaps, not evidence that a particular method was or was not used. Without information about missingness and analysis populations, it is difficult to judge whether the reported counts represent all enrolled participants or a subset for a given measure. Since the primary outcome result itself is not reported, the registry record does not allow assessment of how these issues affected its estimate.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (5.7%), renal artery stenosis (5.7%), adenocarcinoma (2.9%), gastritis (2.9%), hypertension (2.9%).

The adverse-event summary lists 35 participants at risk for serious adverse events, with 7 affected, and 35 at risk for other adverse events, with 23 affected. These are descriptive counts. The registry record does not provide the primary endpoint result alongside them, and they should not be treated as interchangeable with that endpoint.

The primary endpoint is limited to major cardiovascular and/or renal events related to the renal denervation procedure within 30 days post-procedure. By contrast, the adverse-event summary is labeled for renal sympathetic denervation and distinguishes serious from other adverse events. The registry record does not state that every event in those broader categories was procedure-related. The relationship between the broader event counts and the primary endpoint is therefore not reported in the registry record.

The listed serious adverse event terms include atrial fibrillation and renal artery stenosis at 5.7% each, and adenocarcinoma, gastritis, hypertension, and lumbar pain at 2.9% each. These term-specific percentages should be read as descriptions of reported serious event types, not as causal estimates. The registry record does not report whether participants could contribute more than one event term, how terms were coded, or whether the listed terms account for all serious events.

The death count is not reported in the registry record. Neither the counts nor the term percentages provide a comparison with an untreated or alternative-treatment group. They describe events in the study group and do not establish whether the device caused or prevented any event.

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

The registry record documents a prospective, multi-center feasibility study of catheter-based renal denervation using Celsius® ThermoCool® RD in participants with resistant hypertension. It reports an enrollment of 35, identifies a primary safety endpoint, and lists secondary safety and blood pressure outcomes. It also includes descriptive adverse-event counts and selected serious adverse event terms.

Those details establish what the study set out to evaluate and the general structure of its design. They do not establish the observed value of the primary endpoint. The primary result is not reported in the registry record, and no statistical analyses are listed. The record therefore does not show the percentage of participants who experienced the defined procedure-related major event, the uncertainty around that estimate, or the distribution of its components.

The listed adverse-event counts can be read as descriptive observations among the participants at risk. They are not a controlled comparison and should not be interpreted as proof that an event was caused by the procedure. The serious adverse event term percentages also do not replace the primary endpoint because the primary endpoint has a specific event definition, timeframe, and relatedness criterion.

The outcome descriptions for office and ambulatory blood pressure show that the study planned to assess measurements and changes across follow-up. The registry record does not report those measurements or their changes. Consequently, no conclusion about the size, direction, consistency, or precision of a blood pressure change can be drawn from the outcome descriptions alone.

In general, a feasibility study can help describe whether a device intervention was evaluated in a particular study setting and can collect safety and measurement information. The record does not report a comparator, randomization, or masking. Without a control group, observed outcomes cannot distinguish the device’s effect from other influences, and the absence of masking may matter for assessments that involve measurement or judgment. The study’s stated aim to evaluate safety and effectiveness does not itself establish either.

The record also does not report the protocol’s sample-size justification, missing-data methods, or analysis plan. Those omissions limit assessment of how well the available information could answer the study questions. No claim that the device works or does not work, or that its use changes clinical outcomes, follows from the registry information.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between defining a safety outcome and reporting an estimate for it. The registry specifies a primary endpoint with an event definition, a procedure-related criterion, a population, and a follow-up window. Yet the primary endpoint result is not reported in the registry record. Without the observed estimate and its uncertainty, readers cannot evaluate the frequency or precision of the outcome the study designated as primary.

The study also illustrates the limits of descriptive evidence from a single-group design. Counts among treated participants can document what was observed in that group, but they do not supply the counterfactual comparison needed to estimate what would have happened under another approach. This limitation applies to safety events as well as blood pressure measurements. Changes over time may have more than one explanation, and the design does not separate those explanations through randomization.

Another statistical issue is the difference between a broad adverse-event summary and a narrowly defined endpoint. The serious adverse event counts and selected terms provide safety context, but they do not automatically equal procedure-related events meeting the primary definition. Clear reporting of event attribution, component counts, and analysis populations would help readers connect those summaries to the primary question. Those details are not reported in the registry record.

The record lists several secondary outcomes at different follow-up times and in different measurement settings. This breadth makes transparent reporting of missing data, multiplicity, and analysis choices especially important. The registry record does not report those methods or any statistical analyses. The resulting uncertainty is not just about the size of an effect; it also concerns how the listed outcomes would have been analyzed and interpreted.

For biostatisticians and clinical researchers, the key lesson is that design descriptions and outcome definitions are not substitutes for outcome estimates. Interpreting this feasibility study requires distinguishing what was planned or defined from what was observed and analyzed. The registry record provides the former, along with limited adverse-event counts, but leaves the primary result and its statistical precision unavailable.

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 most important limitation for interpreting the registry record is that it does not report the primary endpoint result. The primary safety question is clearly defined, but the observed percentage and the number of participants meeting the definition are not available. The record also does not report a confidence interval or other measure of uncertainty.

The single-group, non-randomized design has no like-for-like control comparison. Any observed events or measurements among participants cannot be directly compared with outcomes under another treatment or no device intervention. The absence of masking is another design feature relevant to how measurements and event attribution might be influenced. The registry record does not describe procedures used to reduce such influences.

The study enrolled 35 participants, but the number contributing to each endpoint is not reported. The primary safety population is defined by enrollment and insertion of the study ablation catheter, but the registry record does not state how many met that definition. Follow-up completion, missing observations, and analysis populations for secondary outcomes are also not reported.

The adverse-event summary does not resolve the primary endpoint question. It reports participants affected by serious and other adverse events and lists selected serious event terms, but the record does not specify the relationship of each broader event count to the primary endpoint’s procedure-related criterion. It also does not report the death count. Event coding and attribution procedures are not described.

The registry record lists no statistical analyses and does not report a statistical analysis plan, missing-data approach, multiplicity strategy, or sample-size justification. It does not provide the secondary blood pressure results or explain how repeated measurements were analyzed. These limitations prevent an assessment of the magnitude and precision of the study outcomes, as well as of the analysis choices used to produce them. They are limits of the information reported in the registry record, not proof that unreported methods or results do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: RENABLATE Feasibility Study CS156 (EC12-02) Study of Catheter Based Renal Denervation to Treat Resistant Hypertension — NCT01756300.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2015-08-25.
• 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

RENABLATE is a completed, prospective, multi-center, non-randomized, single-group Phase 1 feasibility study of catheter-based renal denervation for resistant hypertension. The record lists an enrollment of 35, no masking, and the Celsius® ThermoCool® RD device. The study start is recorded as 2012-12 and primary completion as 2013-11.

The primary endpoint is the percentage of participants with a major cardiovascular and/or renal adverse event related to the procedure within 30 days post-procedure. Secondary outcomes cover adverse events through 12 months and office and ambulatory blood pressure measures at follow-up. The primary result and blood pressure results are not reported in the registry record.

The adverse-event summary lists 7 participants with serious adverse events and 23 with other adverse events, each among 35 at risk. The registry record lists no statistical analyses and does not report a sample-size justification, missing-data methods, or multiplicity approach. The single-group design provides no randomized comparison.