Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD (NCT04458103), a non-randomized na study. The primary outcome is Vasoactive Inotropic Score.

2. Clinical Question

The study asks whether preemptive percutaneous right ventricular assist device (RVAD) placement around left ventricular assist device (LVAD) implantation is associated with different clinical outcomes than standard care in patients undergoing LVAD implantation. Its primary endpoint is the maximum vasoactive-inotropic score (VIS) during the first 24 hours after LVAD implantation. The study description states that the investigators hypothesized RVAD use would reduce VIS by 50%; that is a proposed effect, not a result reported in the registry record.

The registry lists additional outcomes: intensive care unit length of stay, total postoperative length of stay after LVAD implantation, survival at discharge, survival at 1 year after LVAD placement or heart transplant, and end organ dysfunction. The record does not report comparative findings for these outcomes. Since the design is non-randomized and uses a historical comparator, differences between cohorts could reflect factors other than the RVAD strategy. The record does not report outcome estimates with which to assess the size or precision of any difference.

3. Trial Design

This was a non-randomized, parallel-cohort study, with no masking. The prospective interventional cohort consisted of patients undergoing LVAD implantation at Massachusetts General Hospital who were to receive a percutaneous RVAD before or during implantation. The RVAD could be a ProtekDuo or an Impella RP. The comparator was a retrospective cohort of patients who had undergone LVAD implantation in the past. The registry describes the historical controls as age- and sex-matched to the enrolled prospective patients.

The planned comparison was therefore between a contemporaneous prospective intervention cohort and a historical control cohort, not between groups assigned at random under the same enrollment conditions. Matching on age and sex addresses those characteristics as described, but does not establish that the cohorts were otherwise comparable. The registry record does not report details of the matching procedure or other adjustment methods. Allocation was non-randomized, and masking was absent.

The record lists enrollment of 161 and a study status of terminated. It gives a study start date of 2020-05-12 and a primary completion date of 2022-06-01. The reason for termination and whether the intended enrollment or follow-up was completed are not reported in the registry record. The record lists the study phase as NA.

The primary outcome is the maximum vasoactive-inotropic score during the first 24 hours after LVAD implantation. The listed secondary outcomes cover hospital and intensive care stay, survival at discharge, survival at 1 year after LVAD placement or heart transplant, and end organ dysfunction. Six outcome measures are listed, while the record reports no analyses. This means the registry information describes study structure and outcomes but does not provide a comparative outcome analysis to interpret.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Vasoactive Inotropic Score, measured over first 24 hours post-LVAD implantation.

The primary endpoint is the maximum vasoactive-inotropic score (VIS) during the first 24 hours after LVAD implantation. It is a continuous measure based on doses of selected vasopressors and inotropes reviewed in the patient chart. The registry defines the score as dopamine (μg/kg/min) + dobutamine (μg/kg/min) + 10 x milrinone (μg/kg/min) + 100 x epinephrine (μg/kg/min) + 100 x norepinephrine (μg/kg/min) + 10,000 x vasopressin (U/kg/min). The minimum possible score is 0.

The score combines several medications using different weights, so it is not simply a count of drugs or a measure of one medication dose. By recording the maximum within a prespecified postoperative interval, the endpoint is intended to capture the highest level of vasoactive-inotropic support recorded in that period. The registry states that a higher score is hypothesized to correspond with worse outcomes. This is the rationale described for the measure, not a demonstrated relationship in this study.

The record identifies the endpoint as a mean with standard deviation as its dispersion measure. It does not report the cohort means, standard deviations, difference between groups, confidence interval, or statistical test result. Therefore, the extent and precision of any observed comparison cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry specifies a continuous primary endpoint: the maximum VIS during the first 24 hours after LVAD implantation. It identifies the reported summary as a mean and standard deviation. A mean describes the average score in a cohort, while a standard deviation describes the spread of individual scores around that average. These summaries can help describe the distribution, but they do not by themselves show how precisely a difference between cohorts has been estimated.

What would a confidence interval convey?

In general, a confidence interval expresses the uncertainty around an estimated quantity, such as a difference in mean scores. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. It is important to distinguish the interval from the range of individual participant scores. No confidence interval for the primary outcome is reported in the registry record, so the precision of a cohort comparison cannot be evaluated.

What does the non-randomized design imply?

In general, random assignment helps balance both measured and unmeasured participant characteristics across comparison groups, on average. This study instead compares a prospective RVAD cohort with a retrospective historical cohort. The registry describes age and sex matching, but does not report how matching was performed or whether other characteristics were balanced. Matching can address the variables used in the matching process; it does not automatically remove differences in other factors. Without a reported adjusted analysis and adequate information about cohort characteristics, an association between cohort and outcome could not be attributed to the intervention alone.

How should a mean-based comparison be assessed?

In general, a comparison of means should be considered alongside the distribution of the endpoint, the sample sizes contributing outcome data, and the uncertainty interval. A mean can be influenced by unusually high values, especially when a measure is not symmetrically distributed. The VIS is built from medication doses, and the record gives no distribution plots or numerical summaries for either cohort. The appropriate model, any transformation, and any checks of model assumptions are not reported in the registry record. No particular analysis method should therefore be inferred.

General statistical methods for continuous outcomes often rely on assumptions about how observations vary and how the model represents that variation. Over-dispersion, in general, means that observed variability is greater than a model assumes. If a method fails to accommodate the actual variability, its uncertainty estimates may be too optimistic. This is a general consideration, not a claim that over-dispersion occurred in this study. The registry record does not describe a distributional assessment or an approach to over-dispersion.

What do the planning illustrations mean?

The planning illustrations associated with the posted material are not the trial's own design justification. They are described as calculations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect considered is a stated fraction of the observed effect. In general, such calculations estimate how many participants per arm would be needed under the chosen assumptions to attain a specified power for detecting an effect. They are planning illustrations, not observed power and not evidence that the trial was designed or enrolled to meet those assumptions.

The record does not report a sample-size justification, the effect size used in the original design, or a protocol-based power calculation. It also does not provide numeric planning estimates in the information recorded for this analysis. The hypothesized 50% VIS reduction is stated in the study description; it should not be confused with a reported observed effect or a verified design target. If planning figures are considered, their assumptions and their illustrative status matter, and they cannot replace an analysis of the collected outcomes.

What is not available for evaluating the analysis?

The registry lists six outcome measures and reports zero analyses. It does not report the statistical test or model for the primary comparison, covariate adjustment, handling of repeated or incomplete observations, confidence intervals, or p-values. Details of an interim analysis, stopping rule, and analysis population are not reported in the registry record. Without those details and the underlying outcome summaries, neither the statistical significance nor the clinical magnitude of a primary-outcome comparison can be evaluated.

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("Prospective Interventional Cohort", "Retrospective Control Cohort")
n   <- c(17, 144)
m   <- c(36.4, 47.46)
sp  <- c(103.1, 84.8)
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  Prospective Interventional Cohort  17  36.400  103.100  -16.609  89.409
CARM  Retrospective Control Cohort  144  47.460  84.800  33.491  61.429

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary endpoint and several secondary outcomes, but does not report an analysis plan describing how tests across outcomes would be handled. Multiplicity arises when several hypotheses are tested: considering many results can increase the chance that at least one appears statistically notable by chance. In general, a prespecified strategy may distinguish a primary hypothesis from secondary or exploratory analyses, or may adjust for multiple testing. The registry record does not report such a strategy, so it is not possible to determine whether or how multiplicity was addressed.

Missing-data handling is also not reported. The record does not state how absent VIS measurements, incomplete medication records, withdrawals, or unavailable follow-up information were handled. It does not give the number of participants contributing data to each outcome, or describe imputation, complete-case analysis, or sensitivity analyses. These are general analytic choices; none should be assumed for this study.

The record does not define the analysis population for the primary outcome, such as which enrolled participants were included in each comparison. It does not report a protocol or statistical analysis plan that would clarify whether outcome definitions, exclusions, covariates, and analysis methods were set before results were examined. The study's terminated status does not establish how data were handled or why analyses are absent. These omissions limit assessment of the transparency and robustness of any comparison, beyond the fact that no analyses are reported in the registry 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection (45.8%), bleed (38.9%), neurological event (17.6%).

The registry adverse-event record lists a prospective interventional cohort with 17 at risk, 16 affected by serious adverse events, 17 at risk for other adverse events, and 8 affected by other adverse events. For the retrospective control cohort, it lists 144 at risk, 135 affected by serious adverse events, 144 at risk for other adverse events, and 74 affected by other adverse events. Deaths are recorded separately as 4 in the prospective interventional cohort and 13 in the retrospective control cohort.

These are registry counts, not a randomized safety comparison. The groups differ in design and size, and the control cohort is retrospective. The record does not explain the observation period, whether event counts represent people or event episodes beyond the affected and at-risk labels, or the criteria and attribution process used for these entries. It does not report comparative statistical analyses for safety. The listed numbers therefore should not be interpreted as establishing that one strategy caused more or fewer events.

The most frequently listed serious-event terms are Infection, 45.8%; Bleed, 38.9%; and Neurological Event, 17.6%. The registry record does not specify the denominator or aggregation underlying these percentages in the information reported. These terms and percentages should be read as registry listings, not as evidence of causation or comparative risk.

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

The registry record establishes that a non-randomized study was planned to compare a prospective cohort receiving percutaneous RVAD placement around LVAD implantation with a retrospective historical cohort receiving standard care. It identifies maximum VIS during the first 24 hours after LVAD implantation as the primary endpoint and lists additional clinical outcomes. It also records a terminated status and adverse-event counts.

It does not establish whether the RVAD strategy changed VIS, lengths of stay, survival, or end organ dysfunction. No outcome analyses are reported, and the primary cohort means, estimated difference, uncertainty interval, and test result are absent. The proposed 50% reduction in VIS is a hypothesis in the study description, not an observed effect. The safety listings are descriptive registry entries and are not a like-for-like randomized comparison.

Even a reported difference between these cohorts would require cautious interpretation because the allocation was non-randomized and the comparator was historical. Age and sex matching is described, but details and any further adjustment are not reported. Statistical association in such a comparison would not by itself establish a causal effect. In general, an estimate's practical meaning also depends on its magnitude, precision, outcome measurement, and potential sources of bias; the record does not provide enough outcome information to assess those features.

Accordingly, the defensible conclusion is limited to what the record documents about the design, endpoint, planned hypothesis, status, and safety entries. It does not support a conclusion that the intervention did or did not improve any outcome, nor does it quantify uncertainty about an intervention effect.

14. Why This Trial Matters Statistically

This study is statistically notable because its planned comparison combines a prospective intervention cohort with retrospective historical controls. That structure is common in clinical settings where random assignment is not used, but it creates a distinct interpretive challenge: treatment strategy and cohort membership are linked, while the historical comparison may differ in ways not captured by age and sex matching. The record does not report whether other differences were measured or adjusted for.

The primary endpoint also illustrates the distinction between a clinically motivated measure and an analyzed result. VIS combines doses of multiple vasoactive and inotropic medications with specified weights, and the maximum score in a defined postoperative interval was selected as the outcome. The registry describes why the measure was of interest and states a hypothesis, but reports no cohort summaries or comparative estimate. Without those data, the magnitude and precision of any difference remain unknown.

The status of terminated and the absence of reported analyses make transparent reporting especially important. The record does not state why the study ended, whether planned follow-up was completed, or whether outcome data were analyzed outside the registry. Those unknowns are not evidence for a particular explanation. The available information instead demonstrates why a study's design, analysis plan, outcome reporting, and status all matter when interpreting a clinical comparison.

More broadly, sample-size planning illustrations should not be confused with evidence from participants. A calculation based on an assumed effect and model conditions describes a hypothetical planning scenario. It cannot supply the missing observed estimate, nor can it establish whether an analysis was adequately powered in practice. Here, the registry record identifies no analyses from which to assess outcome effects or precision.

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 limitation for interpretation is the absence of reported outcome analyses. No primary endpoint values, comparative estimates, confidence intervals, or p-values are given. The listed secondary outcomes also have no comparative results in the record. As a result, the study's planned clinical question cannot be answered quantitatively from the posted registry information.

The non-randomized design and historical control cohort limit causal interpretation. The registry says controls were age- and sex-matched, but does not report the matching method, participant characteristics, or adjustments for other potential differences. The prospective and retrospective cohorts may also differ in how information was collected; details of measurement consistency are not reported. These are potential design concerns, not claims that a particular bias occurred.

The record does not report why the study was terminated, whether all planned follow-up was completed, or how many participants had usable data for each outcome. Missing-data methods and analysis populations are not described. Nor does the record specify the primary comparison's model, covariates, hypothesis-testing procedure, or approach to the multiple listed outcomes. This prevents assessment of the analysis choices and their assumptions.

The safety entries do not resolve these limitations. Their observation period, event definitions, event attribution, and percentage denominators are not reported in the record. The raw cohort listings are not randomized safety comparisons. Finally, the registry's hypothesis of a 50% VIS reduction should not be read as an outcome estimate or as proof of a prespecified sample-size rationale; that rationale is not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD — NCT04458103.
• Registry record last updated 2024-07-09; status last verified 2024-07.
• Results first posted 2024-07-09.
• 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 registry record describes a non-randomized, unmasked, parallel-cohort study of percutaneous RVAD placement before or during LVAD implantation. Its prospective interventional cohort was compared with a retrospective historical cohort described as age- and sex-matched. The primary endpoint was maximum VIS in the first 24 hours after LVAD implantation.

The record lists enrollment of 161, study status terminated, a start date of 2020-05-12, and a primary completion date of 2022-06-01. It lists secondary outcomes concerning length of stay, survival, and end organ dysfunction. No analyses are reported, and primary outcome results, the reason for termination, and the statistical analysis plan are not reported in the registry record.