Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Study (NCT03170219), a randomized phase 2 study. The primary outcome is Patient Safety Measured by Serious Adverse Events.

2. Clinical Question

The clinical question therefore has two parts in the registry record: whether the device-based strategy could support early discharge while affecting the stated 30-day clinical outcome, and how serious adverse events were counted during the stated follow-up. The posted primary result addresses the latter. It does not report a comparative estimate for days alive and outside the hospital, and the registry record does not report results for the listed secondary outcomes. Eligibility details, baseline participant characteristics, and further information about how the early-discharge objective was operationalized are not reported in the registry record.

3. Trial Design

The SUBQ-HF study is recorded as a phase 2, randomized, parallel-group trial with no masking. The intervention was subcutaneous furosemide with the sc2wear device; the comparator was usual care. Enrollment is recorded as 11, and the study status is terminated. The registry record gives a start date of 2018-04-27 and a primary completion date of 2018-09-20.

The intervention arm description says participants were to receive device training and study materials on the day of randomization, including an SQ pump device and up to a 7 day supply of SQ furosemide vials, and were to be discharged within 24 hours. The treatment instruction that follows in the record is truncated, so the complete planned dosing description is not reported in the registry record. Usual-care participants were to receive inpatient therapy, transition to oral diuretics, and discharge and post-discharge care according to clinician discretion and standard treatment guidelines.

The posted primary outcome is a count of participants with serious adverse events through 30 days. The record lists nine secondary outcomes, including safety, health-care use, breathlessness, and renal function measures. The brief study summary emphasizes days alive and outside the hospital through 30 days, while the posted primary endpoint is serious adverse events; these should not be treated as interchangeable.

Group counts for the posted primary outcome are 7 in the device arm and 4 in usual care. The record does not report details about sequence generation, allocation concealment, blinding of outcome assessment, the rationale for enrollment, or reasons for termination. It also does not report a detailed statistical analysis plan. These omissions limit how fully the design and conduct can be evaluated from the registry record alone.

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 Patient Safety Measured by Serious Adverse Events, measured over 30 days.

The primary endpoint is patient safety measured by serious adverse events, expressed as a count of participants, over 30 days. A participant count indicates how many people in each arm had at least one event meeting the recorded serious-adverse-event definition; it is not a count of every event if a participant experienced more than one. The registry record does not give the detailed event definition, the specific criteria used to classify an event as serious, or a list of serious event terms.

Safety outcomes are used to describe harms observed during a trial and can be particularly relevant when an intervention changes the treatment setting or delivery method. In this study, the intervention strategy included device training and planned early discharge, so recording serious adverse events during follow-up is a distinct question from evaluating days alive and outside the hospital. General statistical context: a participant count is easy to interpret as an observed number, but by itself it does not indicate the precision of a comparison or establish that the underlying risks are equal.

The posted count is 0 in the subcutaneous furosemide and sc2wear device arm and 0 in usual care. Those are the observed serious-adverse-event counts recorded for the stated follow-up. The registry record does not provide a comparative effect estimate or uncertainty interval for this endpoint. It also does not report whether events were independently adjudicated or how incomplete follow-up, if any, was handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a binary outcome: participants either did or did not have a serious adverse event during the stated 30-day timeframe. The posted measure is a participant count. This is a straightforward descriptive summary, but the count alone is not a complete statistical comparison. A comparative analysis would ordinarily relate the event experience in one arm to that in the other and describe the uncertainty around that estimate. No such estimate or uncertainty interval is reported for this endpoint.

What does a confidence interval communicate?

General statistical explanation: a confidence interval expresses the uncertainty associated with an estimated quantity under a specified statistical method. It helps distinguish a result that is estimated precisely from one that remains compatible with a broad range of values. It does not guarantee that the true value lies within a particular interval, and it does not address systematic errors such as incomplete outcome ascertainment. No confidence interval is reported for the primary endpoint in the registry record, so its precision cannot be read from an interval estimate.

Why can a zero count be difficult to compare?

There were no recorded serious adverse events in either arm. General statistical explanation: effect measures based on event rates can be difficult to estimate when one or both groups have zero events. Some common formulas rely on observed events in each group; with zero counts, the estimate may be undefined or highly sensitive to the chosen method. A method that adds a correction or uses a different model can produce an estimate, but its assumptions need to be stated. The registry record does not report such a method or a comparative estimate. The record’s indication that a two-arm comparison is not estimable is consistent with avoiding an unsupported numerical contrast.

What does the randomization contribute?

General statistical explanation: random allocation is intended to make treatment assignment independent of measured and unmeasured participant characteristics on average, reducing the potential for confounding in a comparison. In a small study, chance differences between groups can still occur. The record identifies the study as randomized but does not report the randomization procedure, allocation concealment, or baseline characteristics. It is therefore not possible to assess those aspects of implementation or judge the balance of prognostic characteristics from the registry record.

How should the two arms be understood?

The study is described as parallel-group and unmasked. Each participant was assigned to the device strategy or usual care, rather than receiving both approaches in sequence. No masking was used. General statistical explanation: awareness of assigned treatment can affect care, participant reporting, or assessment, depending on the outcome and how it is measured. The record does not say whether outcome assessors were separately blinded, or whether serious adverse events were adjudicated using a blinded process.

What are planning illustrations?

General statistical explanation: sample-size calculations describe how many participants might be needed under specified assumptions to target a chosen precision or probability of detecting a particular effect. They are planning exercises, not measures of the strength of results already observed. The record describes planning assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It also distinguishes participant-per-arm planning for most outcomes from total-event planning for time-to-event outcomes. No usable two-arm effect estimate is reported for the primary binary endpoint, so the record does not provide an estimable comparison from which to base a planning illustration for that endpoint. Such planning figures, where available for other measures, would not change the observed enrollment or constitute observed power.

The registry record does not report the statistical model for the primary outcome, a prespecified hypothesis test, the handling of zero cells, or a confidence-interval method. It also does not report a sample-size justification. These are important details for interpreting a comparative analysis; they should not be inferred from the design label or from general statistical practice.

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("Subcutaneous Furosemide and sc2wear Device", "Usual Care")
n      <- c(7, 4)
events <- c(0, 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  Subcutaneous Furosemide and sc2wear Device  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  Usual Care  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine secondary outcomes in addition to the primary safety endpoint. They cover a composite safety outcome, medical costs, days alive and outside the hospital through 14 days, heart-failure readmission, emergency department visits, death, breathlessness, and renal function. Results for these secondary outcomes are not reported in the registry record.

When a study evaluates multiple outcomes, general statistical context is that repeated testing can increase the chance of a nominally unusual result arising by chance. Researchers may prespecify a hierarchy or use another approach to account for multiple comparisons. The registry record does not report whether any multiplicity strategy was planned or used. Since secondary results are not posted, no conclusions about those outcomes or their statistical significance can be drawn from the record.

Missing-data handling is also not reported in the registry record. It does not state whether every randomized participant had complete outcome follow-up, how unavailable observations were treated, or whether any imputation or sensitivity analysis was used. The analysis population is not specified, and the record does not say whether results were analyzed according to randomized assignment or another population definition. These omissions matter because incomplete follow-up or differences in analysis populations can affect interpretation, even when the observed event counts are clearly stated.

The record identifies 11 participants as enrolled and gives arm counts for the posted safety results, but does not explain participant flow, withdrawals, exclusions, or the status of follow-up for each participant. It also does not report interim analyses or a detailed statistical analysis plan. Those matters should be treated as not reported in the registry record, rather than assumed to have followed a customary approach.

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 non-serious adverse event terms

For serious adverse events through 30 days, the posted counts are 0 participants in the subcutaneous furosemide and sc2wear device arm and 0 in usual care. The separate other-adverse-event counts are 3 in the device arm and 1 in usual care. Deaths are recorded as 0 in both groups. These categories describe different types of safety information and should be read separately.

The serious adverse event measure is a count of participants, not necessarily a count of every event. The registry record does not provide serious-event terms, detailed definitions, or a comparative estimate with an uncertainty interval. The other-adverse-event terms are not listed in the posted safety summary, so the counts alone do not describe their severity, type, or relationship to treatment.

General statistical context: zero observed events do not prove that no events could occur, and a small study may provide limited precision for safety outcomes. The record reports enrollment of 11 and arm counts of 7 and 4 for the primary result. Those counts support describing what was observed in this study, but they do not establish the frequency of events in a larger population or show that the groups have equivalent safety profiles.

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

The result describes recorded safety outcomes in a small randomized study that was terminated. The primary endpoint count was 0 participants with serious adverse events in the device arm and 0 in usual care during the 30-day timeframe. Deaths were also recorded as 0 in each arm. The registry record separately lists other adverse events for 3 participants in the device arm and 1 in usual care. These observations are the scope of the posted safety data.

They do not show that the two strategies have identical risks. No comparative effect estimate or confidence interval is reported, and the record says a two-arm comparison for the binary outcome is not estimable. General statistical context: an absence of observed events in a limited study can leave considerable uncertainty about the risks that would be observed in a larger group or different setting. The posted counts should not be interpreted as proof of safety or as evidence that serious events cannot occur.

The result also does not answer the study summary’s broader question about days alive and outside the hospital within 30 days. Although that measure is part of the stated objective, results for it are not reported in the registry record. The record lists nine secondary outcomes, but does not report their results. Thus, the safety endpoint cannot be used as a substitute for outcomes relating to hospitalization, symptoms, costs, or renal function.

The study’s randomized design is relevant to its intended comparison, but the registry record does not provide enough information to assess all aspects of conduct and analysis, including baseline characteristics, missing data, or the prespecified statistical approach. The record also does not state why the study was terminated. These limits mean that the posted safety counts are best read descriptively and narrowly: they record what was observed in the trial, without establishing a definitive comparative conclusion or resolving the wider clinical question.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a trial’s clinical objective and the endpoint for which results are posted. The summary describes an early-discharge strategy and days alive and outside the hospital as the intended clinical question, while the recorded primary endpoint is a count of participants with serious adverse events. Those measures address different aspects of care. A safety count alone cannot establish what happened to hospitalization or days outside hospital.

The record also shows why observed counts and comparative inference are not interchangeable. Both arms have zero recorded serious adverse events, but the record does not report a comparative estimate or uncertainty interval and identifies the binary comparison as not estimable. A descriptive result can be reported accurately even when an inferential comparison is unavailable. Avoiding a numerical contrast in that setting helps prevent an unstable or unsupported claim.

The enrollment of 11 and the terminated status are relevant to the scale and context of the evidence. They do not explain why the study ended, whether the enrollment matched a planned target, or how much precision was intended. Those reasons are not reported in the registry record. The registry entries therefore support a careful reading of the recorded outcomes, not speculation about the study’s operational history.

For clinical researchers, this record is a useful reminder to distinguish the endpoint definition, the observed data, and the analysis used to compare groups. It also highlights the value of complete reporting: participant flow, outcome definitions, missing-data methods, and analysis plans help readers judge what an observed count can and cannot establish. In this case, the strongest statistical interpretation is deliberately limited to the posted safety counts and the absence of estimable comparative results.

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 registry record provides limited information for assessing the trial’s conduct and the meaning of the outcome counts. It does not report detailed eligibility criteria, baseline characteristics, participant flow, or reasons for termination. Although the design is identified as randomized, the sequence-generation and allocation-concealment procedures are not reported. The study is identified as unmasked, but the record does not state whether outcome assessment was blinded or whether serious events were adjudicated.

The primary outcome definition is brief. The record does not give detailed criteria for serious adverse events, event-level descriptions, or information about how events were ascertained. The serious-event term list is empty in the posted safety summary. Other adverse events are counted but not described by type. This prevents assessment of what those events involved or whether they were clinically comparable across arms.

Follow-up is stated as 30 days for the primary endpoint, but completeness of follow-up and handling of missing outcome data are not reported. The statistical analysis plan, analysis population, comparative estimation method, and confidence-interval method are also not reported. No primary-endpoint comparative estimate is available, and the registry record indicates that a two-arm comparison for the binary endpoint is not estimable.

The registry lists nine secondary outcomes, but their results are not reported. The summary objective involving days alive and outside the hospital therefore cannot be evaluated from the posted results. The treatment description for the intervention is also truncated, limiting the detail available about the planned regimen. Finally, the registry record does not explain the terminated status or report a sample-size justification. These are limitations of the available record, not evidence that a particular procedure was or was not followed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Study — NCT03170219.
• Registry record last updated 2019-01-23; status last verified 2019-01.
• Results first posted 2019-01-23.
• 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

NCT03170219, titled “Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Study,” is recorded as a randomized, open-label, parallel-group phase 2 trial. It compared subcutaneous furosemide with the sc2wear device against usual care. Enrollment is listed as 11, and study status is terminated. The record lists a start date of 2018-04-27 and primary completion date of 2018-09-20.

The posted primary outcome is participants with serious adverse events through 30 days. The recorded counts are 0 in the device arm and 0 in usual care. Other adverse events were recorded for 3 participants in the device arm and 1 in usual care; deaths were 0 in each arm. A comparative estimate for the primary binary endpoint is not reported as estimable. The record lists nine secondary outcomes but does not report their results. Reasons for termination, the detailed statistical analysis plan, and missing-data handling are not reported in the registry record.