This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for C-Pulse® System: A Heart Assist Device Clinical Study (NCT01740596), a randomized na study. The primary outcome is Primary Safety Outcome.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01740596 |
| Phase | NA |
| Condition | Heart Failure |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 38 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Nuwellis, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with moderate to severe heart failure. The registry record says the study closed early with 38 randomized participants: 19 in the treatment group and 19 in the control group. Further eligibility criteria and details of the enrolled participants are not reported in the registry record.
Intervention
The intervention was C-Pulse® System counterpulsation. The registry identifies this as a device intervention. The primary safety endpoint concerned serious procedure- and device-related adverse events, adjudicated by CEC.
Comparator
The control group received optimal medical therapy. The registry does not report further details about the therapies used in either group or whether they were standardized beyond this description.
Primary question
The study was intended to assess the safety and efficacy of C-Pulse in moderate to severe heart failure, with the stated goal of determining whether the system merited FDA approval to market in the United States. Its primary safety outcome was serious procedure- and device-related adverse events. The registry says this outcome applied only to the implant treatment arm. Because the study closed early and the primary and secondary endpoints were not statistically evaluated, the record does not provide a statistical comparison answering whether outcomes differed between groups.
3. Trial Design
The registry describes a prospective, multicenter, randomized study with parallel groups. Participants were assigned to C-Pulse® System counterpulsation or optimal medical therapy. The masking field is listed as none, so the record does not indicate masking. Details about how randomization was generated or implemented, allocation concealment, and the number or location of centers are not reported in the registry record.
The recorded enrollment is 38, with 19 participants in the treatment group and 19 in the control group. The study status is terminated. The registry says it closed early and that primary and secondary endpoints were not statistically evaluated because the sample size and follow-up were insufficient. The reason for termination and the timing or circumstances of early closure are not reported in the registry record.
The primary safety outcome was defined as serious procedure- and device-related adverse events determined by CEC adjudication, with a 4 Years Follow-up timeframe. The registry states that this endpoint applied only to the implant treatment arm. It also lists secondary outcomes at 12-months: improvement in 6 Minute Hall Walk, LVEF, and KCCQ Score. The record does not provide statistical evaluations of those endpoints.
The study began on 2012-09-12, and primary completion is recorded as 2018-09-19. These registry dates do not by themselves describe each participant’s actual follow-up. Participant-level follow-up duration and reasons for any incomplete follow-up 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
| Stage | C-Pulse® System Treatment Group | Control Group |
|---|---|---|
| STARTED | 19 | 19 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 19 | 19 |
Analysis population for the primary outcome, as defined in the registry: Study was closed early with only 38 randomized subjects (19 treatment group and 19 control). Primary and secondary endpoints were not statistically evaluated as there was insufficient sample size and follow-up. The primary safety outcome was only applicable to the implant treatment arm as it is specifically measuring device and/or procedure related serious adverse events (control arm was treated as standard of care and did not undergo a procedure for the study device to be placed).
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: Study was closed early with only 38/388 (9.8%) subjects enrolled and Baseline Characteristics were analyzed collectively across both treatment arms of the study. A total of 38 patients were randomized, however, 3/38 patients randomized to the Treatment Arm were withdrawn from the study prior to implant occurring and were not included in the final analysis. The overall number of baseline participants analyzed was 35/38.
| Characteristic | Unit | Study Participants |
|---|---|---|
| Participants analysed | 35 | |
| Age, Continuous: Treatment Arm | years | 63.3 (SD 11.7) |
| Age, Continuous: Control Arm | years | 58.5 (SD 8.2) |
| Sex: Female, Male: Treatment Arm – Female | Participants | 2 |
| Sex: Female, Male: Treatment Arm – Male | Participants | 15 |
| Sex: Female, Male: Control Arm – Female | Participants | 4 |
| Sex: Female, Male: Control Arm – Male | Participants | 14 |
| Race/Ethnicity, Customized: Treatment Arm – Black or African American | Participants | 5 |
| Race/Ethnicity, Customized: Treatment Arm – Caucasian | Participants | 9 |
| Race/Ethnicity, Customized: Treatment Arm – Not Disclosed | Participants | 3 |
| Race/Ethnicity, Customized: Control Arm – Black or African American | Participants | 8 |
| Race/Ethnicity, Customized: Control Arm – Caucasian | Participants | 9 |
| Race/Ethnicity, Customized: Control Arm – Not Disclosed | Participants | 1 |
| Region of Enrollment: United States | Participants | 35 |
| Intermacs Subject Profile/Status: Treatment Arm – 4: Resting Symptoms | Participants | 0 |
| Intermacs Subject Profile/Status: Treatment Arm – 5: Exertion Intolerant | Participants | 6 |
| Intermacs Subject Profile/Status: Treatment Arm – 6: Exertion Limited | Participants | 7 |
| Intermacs Subject Profile/Status: Treatment Arm – 7: Advanced NYHA Class III | Participants | 3 |
| Intermacs Subject Profile/Status: Treatment Arm – Not Available | Participants | 1 |
| Intermacs Subject Profile/Status: Control Arm – 4: Resting Symptoms | Participants | 4 |
| Intermacs Subject Profile/Status: Control Arm – 5: Exertion Intolerant | Participants | 3 |
| Intermacs Subject Profile/Status: Control Arm – 6: Exertion Limited | Participants | 7 |
| Intermacs Subject Profile/Status: Control Arm – 7: Advanced NYHA Class III | Participants | 1 |
| Intermacs Subject Profile/Status: Control Arm – Not Available | Participants | 3 |
| NYHA Classification: Treatment Arm – Class I | Participants | 0 |
| NYHA Classification: Treatment Arm – Class II | Participants | 0 |
| NYHA Classification: Treatment Arm – Class III | Participants | 17 |
| NYHA Classification: Treatment Arm – Class IV | Participants | 0 |
| NYHA Classification: Control Arm – Class I | Participants | 0 |
| NYHA Classification: Control Arm – Class II | Participants | 0 |
| NYHA Classification: Control Arm – Class III | Participants | 18 |
| NYHA Classification: Control Arm – Class IV | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Primary Safety Outcome, measured over 4 Years Follow-up.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was a safety measure: serious procedure- and device-related adverse events, determined by CEC adjudication. The stated timeframe was 4 Years Follow-up. The registry describes the outcome as a count of participants and says it applied only to the implant treatment arm. It also states that there were no formal statistical hypotheses for this endpoint.
In general, a safety endpoint helps characterize harms associated with a procedure or device. Restricting the endpoint to serious events focuses attention on events classified as serious and related to the procedure or device, rather than treating every reported health event as part of the primary outcome. Adjudication provides a specified process for determining whether an event meets the endpoint definition; the registry does not report further details about the adjudication process.
The registry record does not report a statistical evaluation of the primary endpoint. It says the study closed early with 38 randomized participants and that primary and secondary endpoints were not statistically evaluated because the sample size and follow-up were insufficient. Therefore, the endpoint definition and timeframe describe what was intended to be assessed, but the record does not provide an inferential estimate of the primary outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The most important interpretive fact is that the registry explicitly says the study closed early and its primary and secondary endpoints were not statistically evaluated because the sample size and follow-up were insufficient. The record therefore does not present a statistical test or estimated treatment effect for the intended primary safety endpoint. It also does not establish a statistical comparison of the secondary outcomes.
The adverse-event information is descriptive. The registry reports serious adverse events affecting 16 participants in the treatment group and 15 in the control group. It reports other adverse events affecting 9 in the treatment group and 1 in the control group, and deaths of 10 and 5, respectively. These entries are counts, not a reported inferential comparison. Without a statistical evaluation and details about event definitions, timing, follow-up completeness, and analysis populations, they should not be read as estimates of a causal treatment effect.
The primary safety endpoint is not interchangeable with the overall serious-event entries. It is defined specifically as serious procedure- and device-related adverse events adjudicated by CEC, and the registry says it applied only to the implant treatment arm. The serious-event counts describe the registry’s adverse-event reporting by group, but the record does not establish that those counts are identical to the endpoint as defined. Nor does it report a formal comparison for that endpoint.
The listed serious-event terms include Worsening Heart Failure (68.4%), Cardiac Disorders (57.9%), Renal or Neuro Dysfunction (42.1%), Major Infection (31.6%), Respiratory Failure (5.3%), and Device Malfunction (5.3%). These are reported as top serious terms. The record does not specify in this listing the denominator, whether categories overlap, or the exact statistical method used to derive the percentages. They should therefore be treated as descriptive registry entries rather than as mutually exclusive categories or as evidence of a between-group difference.
The status is terminated, and the registry gives no reason for termination. No confidence intervals, p-values, adjusted estimates, or other inferential results are reported. The record supports a description of the study design, early closure, and posted adverse-event figures; it does not support a conclusion about comparative efficacy or a statistically established difference in safety.
9. Statistical Methods Explained
The design is randomized and parallel-group: participants were assigned to C-Pulse® System counterpulsation or optimal medical therapy, and the registry records no masking. Randomization is generally used to make treatment groups comparable with respect to measured and unmeasured characteristics on average. It does not guarantee balance in any particular trial, especially when enrollment is limited. The registry does not report the sequence-generation method, allocation concealment, stratification, or other implementation details, so those features cannot be assessed from this record.
The primary outcome is a count of participants meeting a safety definition. This differs from an outcome that records repeated events: a participant-count endpoint ordinarily concerns whether a participant met the definition, while an event-count endpoint may include multiple occurrences. Here, the registry identifies the primary outcome as a count of participants and defines it as serious procedure- and device-related adverse events adjudicated by CEC. It does not report participant-level data or explain how multiple qualifying events for the same participant were handled.
The registry says there were no formal statistical hypotheses for the primary safety endpoint. It also says primary and secondary endpoints were not statistically evaluated because the study closed early with 38 randomized participants and insufficient sample size and follow-up. Accordingly, there is no reported primary-endpoint hypothesis test or treatment-effect estimate to interpret. A confidence interval, in general, expresses uncertainty around an estimate under a statistical model; it is not a substitute for a complete description of the endpoint, population, and analysis. No primary-outcome confidence interval is reported in the registry record.
The adverse-event counts are descriptive. A count alone does not quantify the uncertainty around a comparison, account for follow-up duration, or demonstrate that group differences are attributable to treatment assignment. In general, event rates can be affected by time at risk, how events are defined and collected, and whether participants have complete observation. Those details are not reported for these adverse-event entries. The deaths are also listed as counts; cause, timing, and the analysis approach are not reported in the registry record.
The serious-event term percentages are also descriptive listings. The registry identifies the terms and percentages but does not report the denominators or whether a participant could contribute to more than one term. In general, adverse-event categories can overlap, so percentages across terms should not be added or assumed to represent separate groups of participants. The listed terms do not provide an inferential comparison between treatment and control.
General statistical interpretation also depends on distinguishing statistical uncertainty from the clinical importance of an effect. A small study may yield imprecise estimates, while a large study may estimate a small effect precisely; neither precision nor importance can be assessed from counts alone. The registry does not provide estimated effects or uncertainty intervals for the primary or secondary endpoints. Since the stated reason endpoints were not evaluated includes insufficient sample size and follow-up, the adverse-event figures should not be recast as evidence that a treatment effect was absent or established.
The record includes planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. Such calculations are planning illustrations based on assumptions, not observed power and not a retrospective demonstration that the study could or could not detect a particular effect. The registry does not report a sample-size justification for the original trial design. Any planning illustration should be read separately from the actual enrollment and from the unperformed statistical evaluation.
Over-dispersion is a general concern when count data vary more than a chosen model expects; ignoring it can make uncertainty appear too small. That issue is not something that can be diagnosed from the registry’s participant counts alone, and the record does not report a model for the adverse-event data. More broadly, the statistical analysis plan, model specifications, covariate adjustments, missing-data methods, and analysis populations are not reported in the registry record. These omissions limit assessment of how an inferential analysis would have been conducted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and secondary outcomes concerning 6 Minute Hall Walk, LVEF, and KCCQ Score at 12-months. It says there were no formal statistical hypotheses for the primary safety endpoint and that the primary and secondary endpoints were not statistically evaluated. A multiplicity strategy for interpreting several endpoints is not reported in the registry record. Without reported tests or an analysis plan, there is no basis to describe adjustment for multiple comparisons or to treat any endpoint as a statistically confirmed finding.
Missing-data handling is not reported in the registry record. The record says follow-up was insufficient, but does not say how many participants had incomplete outcome data, why observations were missing, or whether any imputation or other method was planned or used. In general, missingness can affect an estimate if the availability of outcome data is related to treatment or participant status. No such relationship can be assessed from the posted information.
Analysis populations are also not reported in the registry record. The record gives the randomized group sizes and says the primary safety outcome applied only to the implant treatment arm, but it does not specify an intention-to-treat, per-protocol, or other population for analysis. It records no analysis entries. These gaps mean the posted counts should not be assumed to represent a particular prespecified statistical population or method.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment Group | 16 | 19 | 84.2% |
| Control Group | 15 | 19 | 78.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Group | 10 of 19 |
| Control Group | 5 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment Group | 9 of 19 |
| Control Group | 1 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Group | Control Group |
|---|---|---|---|
| Worsening Heart Failure | Cardiac disorders | 13 of 19 | 13 of 19 |
| Cardiac Disorders | Cardiac disorders | 11 of 19 | 10 of 19 |
| Renal or Neuro Dysfunction | General disorders | 8 of 19 | 5 of 19 |
| Major Infection | Infections and infestations | 6 of 19 | 3 of 19 |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | 1 of 19 | 0 of 19 |
| Device Malfunction | Product Issues | 1 of 19 | 0 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Group | Control Group |
|---|---|---|---|
| General Disorders | General disorders | 4 of 19 | 1 of 19 |
| Cardiac Disorders | Cardiac disorders | 4 of 19 | 0 of 19 |
| Infection | Infections and infestations | 4 of 19 | 0 of 19 |
Serious events with the highest arm-level rate: worsening heart failure (68.4%), cardiac disorders (57.9%), renal or neuro dysfunction (42.1%), major infection (31.6%), respiratory failure (5.3%).
The registry reports serious adverse events affecting 16 participants in the treatment group and 15 in the control group. It separately reports other adverse events affecting 9 in the treatment group and 1 in the control group, and deaths of 10 and 5, respectively. These are descriptive counts. The registry does not report an inferential analysis of these entries, so they do not establish a statistically evaluated difference between groups.
The primary safety endpoint has a narrower definition: serious procedure- and device-related adverse events determined by CEC adjudication. The record states that this endpoint applied only to the implant treatment arm. It should not be assumed that the overall serious adverse-event counts are the same measure as this primary endpoint. The record does not report a statistical evaluation of the primary endpoint.
The listed serious terms and percentages are Worsening Heart Failure (68.4%), Cardiac Disorders (57.9%), Renal or Neuro Dysfunction (42.1%), Major Infection (31.6%), Respiratory Failure (5.3%), and Device Malfunction (5.3%). The record does not specify the denominator for these percentages or whether categories overlap. They are therefore best read as descriptive term listings, not as independent categories that can be added together. Details about event timing, severity criteria beyond the serious classification, causes of death, and completeness of follow-up are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry establishes that a randomized, parallel-group study of C-Pulse® System counterpulsation versus optimal medical therapy was conducted in patients with moderate to severe heart failure and later terminated. It records 38 randomized participants, split as 19 in the treatment group and 19 in the control group. It also records adverse-event counts and a list of serious-event terms.
Those details do not amount to a statistical finding that one group had better or worse outcomes. The registry explicitly states that the study closed early and the primary and secondary endpoints were not statistically evaluated because the sample size and follow-up were insufficient. No treatment-effect estimate, confidence interval, or p-value is reported for the primary endpoint. The absence of an inferential result is not evidence that the groups were equivalent, and the raw adverse-event counts cannot by themselves establish a causal effect.
The intended primary safety measure was serious procedure- and device-related adverse events, determined by CEC adjudication, with a 4 Years Follow-up timeframe. The registry says this measure applied only to the implant treatment arm. That definition differs from a broad comparison of all adverse events, and the record does not show a formal statistical evaluation of the endpoint.
The registry also lists improvement in 6 Minute Hall Walk, LVEF, and KCCQ Score at 12-months as secondary outcomes. It does not provide statistical evaluations for these outcomes. The record therefore does not establish an efficacy result or a comparative conclusion for those measures. The reason for termination, participant-level follow-up, missing-data methods, and analysis populations are not reported in the registry record. Interpretation should remain limited to the study description and descriptive results that are posted.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized design and a reported statistical result are not the same thing. Random assignment can support a comparative question, but answering that question requires outcome data and an analysis appropriate to the endpoint and the available follow-up. The registry says this study closed early and that the primary and secondary endpoints were not statistically evaluated because the sample size and follow-up were insufficient. Consequently, the design alone does not supply an estimate of comparative safety or efficacy.
The distinction between an endpoint definition and a posted result is also important. The primary safety endpoint was defined as serious procedure- and device-related adverse events adjudicated by CEC, and it applied only to the implant treatment arm. That prespecified focus is not interchangeable with every adverse event or with the group-level event counts. Keeping these measures separate avoids attributing a formal endpoint interpretation to descriptive entries.
The record also highlights the limits of interpreting counts without details about time at risk, missing observations, event definitions, and analysis populations. These considerations matter for safety reporting because participants may have different observation histories, and event categories may overlap. The registry does not report enough detail to resolve those questions or to assess inferential uncertainty.
Finally, planning calculations and observed evidence answer different questions. A sample-size illustration based on assumptions can help describe what a future design might require, but it cannot replace analysis of the trial’s outcomes or establish the precision achieved by this study. The posted record is therefore informative about study conduct and recorded adverse events, while leaving the comparative statistical question unresolved.
14. 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 reports early closure and insufficient sample size and follow-up as the reasons the primary and secondary endpoints were not statistically evaluated. It does not report why the study was terminated or provide further details about the circumstances of closure. This limits interpretation of how the completed study came to differ from its intended assessment.
The record does not provide participant-level outcomes, estimates of treatment effects, uncertainty intervals, or formal tests. It also does not report the statistical analysis plan, analysis populations, missing-data approach, or the method for handling multiple endpoints. The randomized group sizes are recorded, but eligibility criteria, baseline characteristics, adherence, and treatment exposure details are not reported in the registry record.
Follow-up is particularly relevant because the primary endpoint timeframe is 4 Years Follow-up, while the record says follow-up was insufficient. The actual follow-up duration by participant and completeness of outcome ascertainment are not reported. The timing, causes, and definitions associated with the death counts are also not reported.
The serious-event term percentages lack a reported denominator and information about overlap between categories. The registry does not explain the relationship between these entries and the more narrowly defined primary safety endpoint. These limitations prevent a reconstruction of comparative risks or a determination of statistical precision from the posted figures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: C-Pulse® System: A Heart Assist Device Clinical Study — NCT01740596.
- Registry record last updated 2024-01-11; status last verified 2023-08.
- Results first posted 2024-01-11.
- 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.
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18. Record Summary
NCT01740596 is a randomized, parallel-group study of C-Pulse® System counterpulsation versus optimal medical therapy for moderate to severe heart failure. The registry records 38 randomized participants, with 19 in each group, and a status of terminated. The primary safety endpoint concerned serious procedure- and device-related adverse events adjudicated by CEC, with a 4 Years Follow-up timeframe; the registry says it applied only to the implant treatment arm.
The registry says the study closed early and that primary and secondary endpoints were not statistically evaluated because sample size and follow-up were insufficient. It posts adverse-event counts and serious-event terms, but no inferential comparison. The reason for termination and details of the statistical analysis plan, missing-data handling, and analysis populations are not reported in the registry record.