The CASCADE HF Soft Launch and Calibration Phase I and II: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The CASCADE HF Soft Launch and Calibration Phase I and II (NCT04738279), a non-randomized phase 2, phase 3 study. The primary outcome is Attrition Rate.

2. Clinical Question

The study concerns people with heart failure in the period after hospital discharge, when the registry describes patients as vulnerable to readmission. It examines a non-invasive wearable monitoring approach linked to a structured escalation pathway. The registry’s stated broader aim is to determine whether continuous ambulatory wearable technology and cascading alerts can reduce 30-day readmission in high-risk patients. The primary outcome listed, however, is attrition from the study within 30 days of discharge; readmission is listed as a secondary outcome.

The record therefore identifies an implementation and calibration effort as well as a clinical objective. It does not report enough outcome information to determine attrition, readmission, or diuretic escalation rates from the registry record.

3. Trial Design

The registry lists the study as Phase 2 and Phase 3, with a non-randomized allocation, no masking, and a sequential model. It reports an enrollment of 20 and a completed status. The listed study dates are 2020-12-14 for the start and 2021-10-30 for primary completion. The sponsor is Endeavor Health.

The design description divides the work into two successive phases. Phase I, called Soft Launch, is described as lasting 120 days and involving the first five heart failure patients enrolled, with the purpose of fine-tuning processes and protocol. Phase II, called Calibration, is described as lasting 210 days. It follows learning from the soft launch and protocol updates, and is described as enrolling 15 additional patients for calibration. The record’s overall enrollment is 20.

Because recruitment and study activity proceed sequentially, the phases should not be read as randomized treatment groups or as concurrent control and intervention arms. The first group is used for process refinement, and the later group follows protocol updates. Changes in procedures and the order of enrollment mean that a simple contrast between the phase counts would not establish a treatment effect. The record does not report a randomized comparison.

The study description links wearable monitoring to remote follow-up and a cascading escalation pathway involving home health nurses, advanced practitioner providers, specialists, and surgeons. The registry lists two interventions: Non-Invasive Continuous Remote Patient Monitoring and Affective Analysis of Participant Response to Continuous Remote Patient Monitoring. Further details of the allocation procedures, eligibility criteria, adherence definitions, and statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

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

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 Attrition Rate, measured over 30 days from patient discharge date.

The primary outcome is Attrition Rate, expressed as a count of participants. Its description is “Drop out from study,” and its timeframe is 30 days from the patient discharge date. This endpoint captures whether participants remain engaged in the study over the specified follow-up period, rather than directly measuring a clinical event such as readmission.

Attrition is useful to report in a remote-monitoring study because participation requires ongoing contact with a monitoring system and study procedures. A count of dropouts can describe the feasibility of retaining participants during follow-up. It can also inform how completely other outcomes are observed, since participants who leave may have less follow-up information available. These are general reasons for tracking attrition; the registry does not report the study’s specific rationale for choosing this endpoint.

The endpoint is defined as a participant count, but the registry record does not report an attrition result or further operational details, such as the criteria used to classify a participant as having dropped out. It also does not report whether withdrawal, loss to follow-up, device non-use, or another event counted as attrition. Without those definitions and the observed count, the endpoint cannot be interpreted as a rate or compared across phases from the registry record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count tell the reader?

General statistical explanation: A count records how many participants meet an outcome definition. For a binary outcome, each participant is classified as either having or not having the event over the defined observation period. The count is directly interpretable as a number of participants, but a count alone does not describe the event frequency unless the number of participants with outcome information is also known. It also does not show how precisely the underlying event frequency has been estimated.

The primary outcome in this record is a count of participants who drop out within 30 days after discharge. The record does not report the observed primary-outcome count or detailed classification rules. It therefore does not support a calculation or interpretation of attrition frequency from the registry record.

Why distinguish a count from a rate or risk?

General statistical explanation: A count is the number of events or people meeting a definition. A risk or proportion relates that count to the number of people eligible for assessment over a defined period. A rate may also account for time under observation. These summaries answer different questions, and their interpretation depends on clear outcome definitions, denominators, and follow-up. The registry identifies the attrition outcome as a participant count and gives a 30-day timeframe, but does not report an attrition denominator with outcome data or an observed result.

For readmission, a participant-level binary outcome would ordinarily distinguish participants with and without a readmission during the stated follow-up period. That is a general description, not a claim about the analysis used in this study. Readmission is listed as a secondary outcome, but its definition, denominator, and result are not reported in the registry record.

What can an uncertainty interval add?

General statistical explanation: A confidence interval gives a range of values compatible with the data under a specified statistical method. It communicates precision as well as the estimate itself. Wider intervals indicate less precision, while narrower intervals indicate more precision, conditional on the model and data. An interval does not by itself remove bias from a non-randomized design, correct missing data, or establish that groups are comparable.

The registry record does not report confidence intervals or other uncertainty intervals for the primary or secondary outcomes. Without outcome estimates and their uncertainty, the clinical outcomes cannot be judged for precision from this record.

Why does the study structure matter for comparisons?

General statistical explanation: Random allocation can, on average, balance measured and unmeasured participant characteristics between study groups. A non-randomized comparison does not have that protection. Sequential groups can also differ because they enter at different times or experience different procedures. When a protocol changes between phases, the phase contrast may combine the effects of those changes with differences in participants, follow-up, or implementation.

Here, the registry describes a soft launch followed by calibration after learning from the initial phase and updating the protocol. The record explicitly identifies the allocation as non-randomized. The phases are therefore best understood as stages of study development, not as a like-for-like control comparison. No adjusted analysis or method for handling phase differences is reported in the registry record.

How should planning illustrations be read?

General statistical explanation: A sample-size planning illustration asks how many participants might be needed under specified assumptions to detect a particular effect with a chosen statistical procedure. Such an illustration depends on assumptions about the effect size, significance level, allocation, outcome distribution, and analytic method. It is not a measure of the probability that a completed study has discovered an effect, and it is not “observed power.”

The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a specified fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events using the Schoenfeld method; for other outcomes, the convention is participants per arm. These are planning conventions, not evidence that the trial used a randomized two-arm design. The record does not report a trial-specific sample-size justification or the observed effect needed to interpret those planning illustrations.

Since the phases are sequential and not randomized, an equal-allocation planning assumption should not be mistaken for the study’s actual design. Planning outputs under assumptions are hypothetical quantities. They cannot replace outcome estimates, uncertainty intervals, or a clear account of the analysis performed.

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("Phase I: Soft Launch (120 Days)", "Phase II: Calibration (210 Days)")
n      <- c(5, 15)
events <- c(1, 2)
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  Phase I: Soft Launch (120 Days)  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  Phase II: Calibration (210 Days)  15  2  13.3  1.7  40.5  3.7  37.9  4.0  38.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and zero analyses. It names Attrition Rate as the primary outcome and lists Number of Participants With Diuretic Escalation and 30-day Readmission as secondary outcomes. The record does not identify the remaining outcome measure in the registry record for this summary, and it does not report results for the listed outcomes.

Multiplicity refers, in general, to the interpretive problem created when multiple outcomes, comparisons, time points, or statistical tests are considered. The chance of at least one apparently notable result can increase as the number of analyses grows. A statistical plan may specify which outcome is primary, which analyses are confirmatory or exploratory, and whether any adjustment or hierarchy is used. The registry record does not report a multiplicity strategy, so it is not possible to determine how the listed outcomes were prioritized analytically or how multiple tests were handled.

Missing-data methods are also not reported in the registry record. The primary outcome concerns dropout, making it particularly relevant to know how participants with incomplete follow-up were classified and whether outcome information was sought after study withdrawal. The record does not explain whether missing values were excluded, imputed, or handled in another way. Those choices can affect estimates, especially when missingness is related to participant experience or outcome status; this is a general statistical consideration, not a reported feature of this study.

The analysis populations are not reported in the registry record. It is therefore unclear which enrolled participants would have been included in each outcome analysis, how protocol deviations were handled, or whether analyses followed an intention-to-treat, per-protocol, or other definition. No particular population or missing-data procedure should be assumed.

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.

The registry reports separate adverse-event counts for Phase I: Soft Launch and Phase II: Calibration. In Phase I, five participants were listed as at risk for serious adverse events, with zero affected; five were listed as at risk for other adverse events, with zero affected; and deaths were zero. In Phase II, 15 participants were listed as at risk for serious adverse events, with zero affected; 15 were listed as at risk for other adverse events, with zero affected; and deaths were zero.

These entries describe what the registry record reports for the listed groups. They do not mean that the study established the absence of all possible harms. The record does not provide event definitions, collection procedures, follow-up completeness, or detail about how adverse events were reviewed. It also does not report individual event descriptions; no top serious-event terms are listed.

Zero affected is a descriptive count, not proof that the true risk is zero. General statistical explanation: When few participants are observed, uncommon events may not occur in the study even if they could occur in a larger population. Precision around safety estimates depends on the amount and completeness of follow-up as well as the event count. These registry figures should therefore be read as reported counts for this study, not as a definitive estimate of safety in a broader population.

The adverse-event figures are not the attrition endpoint and do not provide results for readmission or diuretic escalation.

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

The registry record documents a completed study of non-invasive continuous remote patient monitoring in heart failure patients, organized as a soft launch followed by a calibration phase. It reports an enrollment of 20, with the phase descriptions specifying five patients for the initial soft launch and 15 for the subsequent calibration. The intervention concept includes wearable monitoring and a cascading escalation pathway. The stated clinical motivation is to examine whether this approach can reduce 30-day readmission after discharge.

What the record does not establish is the size or direction of any clinical outcome. Attrition is the primary outcome, and 30-day readmission and participants with diuretic escalation are secondary outcomes, but their results are not reported in the registry record. Thus the record does not show how many participants dropped out, how many were readmitted, or how many had diuretic escalation. It also does not report estimates or uncertainty intervals that would indicate the precision of such results.

The zero adverse-event counts are descriptive and limited to the listed groups and categories. They do not demonstrate that adverse events are impossible or that monitoring has a particular benefit or harm. The lack of a randomized comparison further limits causal interpretation: phase differences could reflect the sequential study process, including protocol learning and updates, as well as other differences between participants or follow-up.

General statistical interpretation: A study can be valuable for learning about implementation and refining procedures even when its design does not support a strong causal comparison. In such settings, outcome definitions, complete follow-up, transparent denominators, and precise reporting are especially important. Those details are not reported in the registry record for the primary and secondary outcomes.

The most limited conclusion supported by the record is that it describes the design, purpose, enrollment, and selected safety counts of a completed sequential study. It does not report enough outcome information to determine whether the stated readmission objective was achieved.

14. Why This Trial Matters Statistically

This study is statistically notable because the stated clinical objective and the registered primary outcome are not the same endpoint. The official title focuses on reducing 30-day readmission, while the primary outcome is Attrition Rate within 30 days from discharge. Readmission is listed as a secondary outcome. Keeping the distinction clear prevents a reader from treating a feasibility or retention measure as a clinical readmission result.

The sequential structure also matters. The soft launch is intended to refine processes and protocol, and the calibration phase follows learning and protocol updates. This design can support development and operational learning, but it does not create a randomized comparison. Any phase contrast would need to be interpreted in light of that sequence and the intervening changes. The registry does not report such a result or an analysis plan.

For a remote-monitoring intervention, retention and missing follow-up are statistically relevant because interpretation of clinical outcomes depends on knowing who contributed outcome information. The registry names attrition as the primary measure, but does not report its result or definitions. Readmission and diuretic escalation results are also not reported. That makes transparent outcome reporting central to judging both feasibility and clinical outcomes.

The registry’s adverse-event counts add a descriptive safety record, but small participant counts and the absence of event detail limit what those entries can establish. General statistical reasoning cautions against interpreting zero observed events as proof of zero underlying risk.

Overall, the study raises useful design and reporting questions: whether the monitoring workflow can be implemented, how attrition is defined, and how outcome data are analyzed across changing phases. The registry record establishes the questions and structure, but not the clinical outcome estimates needed to answer the readmission question.

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 primary limitation for interpreting outcomes is that the registry record does not report results for attrition, 30-day readmission, or diuretic escalation. It therefore does not supply event counts, denominators, effect estimates, or uncertainty intervals for these outcomes. The overall enrollment of 20 does not fill that gap.

The study is non-randomized and sequential. Phase I is described as a soft launch for process and protocol refinement; Phase II follows learning and protocol updates. This makes the phases unsuitable as a straightforward randomized treatment-versus-control comparison. The registry record does not report methods for adjusting for differences between phases or participants.

The outcome information is incomplete for statistical interpretation. The attrition endpoint is described as drop out from study within 30 days of discharge, but the registry record does not give the operational definition, observed count, or handling of participants with incomplete follow-up. It does not report the analysis populations, missing-data methods, or statistical analysis plan. The multiplicity approach for the listed outcomes is also not reported.

The record lists four outcome measures and zero analyses. It does not report the results of the secondary outcomes or provide detail about the remaining outcome measure in the registry record for this summary. The adverse-event entries include zero affected participants and zero deaths in the listed phases, but do not provide event definitions, collection methods, or detailed follow-up information. These limitations constrain both efficacy interpretation and safety precision.

Finally, the study’s rationale describes a monitoring and escalation pathway, but the registry record does not report adherence, device-use, alert, or escalation-process results. Such operational detail would help interpret how the intervention was implemented, but none should be inferred from the study description alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The CASCADE HF Soft Launch and Calibration Phase I and II — NCT04738279.
• Registry record last updated 2023-10-03; status last verified 2023-10.
• Results first posted 2023-02-16.
• 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

NCT04738279 is a completed, non-randomized, unmasked, sequential study sponsored by Endeavor Health. It is listed as Phase 2 and Phase 3 and reports enrollment of 20. The study is organized into a Phase I soft launch, described as involving five patients, and a Phase II calibration phase, described as involving 15 patients.

The study evaluates non-invasive continuous remote patient monitoring and affective analysis of participant response to monitoring. Its stated objective concerns wearable technology, cascading alerts, and 30-day readmission in high-risk heart failure patients. Attrition within 30 days of discharge is the primary outcome; diuretic escalation and 30-day readmission are listed as secondary outcomes.

The registry reports zero serious adverse events, zero other adverse events, and zero deaths in the listed phase groups. It does not report primary or secondary outcome results, analysis methods, or a multiplicity and missing-data plan. The record therefore describes the study design and selected safety counts but does not establish the clinical outcome findings.