This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
BREATHE-1 was a first-in-human study of the Apreo Implant in patients with emphysema or COPD. The registry describes a single-group, unmasked treatment study with 48 enrolled participants and one intervention arm.
| Feature | BREATHE-1 |
|---|---|
| Official title | First in Human Study to Assess an Implant to Treat Severe Emphysema |
| Phase | NA |
| Condition | Emphysema or COPD |
| Design model | Single-group |
| Allocation | NA |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 48 |
| Number of arms | 1 |
| Intervention | Apreo Implant Group (device) |
| Lead sponsor | Apreo Health, Inc. |
| Sponsor type | Industry |
| Status | Completed |
| Study start | 2023-05-05 |
| Primary completion date | 2024-10-08 |
| ClinicalTrials.gov | NCT05854550 |
2. Clinical Question
The clinical question in BREATHE-1 is centered on the safety of an implant intended to treat severe emphysema. The registry identifies the study as a treatment study in people with emphysema or COPD and defines a primary endpoint based on serious adverse events related to the device and/or study procedure.
Population
Participants enrolled in a first-in-human study for emphysema or COPD.
Intervention
Apreo Implant Group (device).
Comparator
No separate comparator arm was specified; the design model is single-group.
Primary question
What is the rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure?
3. Trial Design
Apreo Implant Group
- Intervention type: device
- Study design: single-group
- Number of study arms: 1
- Masking: none
No separate comparator arm
- The registry describes a single-group design.
- Allocation is listed as NA.
- The primary endpoint is therefore evaluated within the treated study population rather than as a randomized between-group comparison.
4. Trial Timeline
Study start
BREATHE-1 began as a first-in-human study of an implant intended to treat severe emphysema.
Primary completion
The registry lists October 8, 2024 as the primary completion date.
Completed
The registry identifies the study status as completed.
5. Primary Endpoint
| Endpoint | Time frame | Registry definition |
|---|---|---|
| Rate of Serious Adverse Events (SAE) at 6 Months | 6 Months | Rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure |
The primary endpoint is a safety-rate endpoint rather than a time-to-event efficacy endpoint. Its focus is the occurrence of serious adverse events that are related to the study device and/or study procedure during the specified 6-month period after the study procedure.
For a single-group safety study, the resulting proportion describes the observed frequency of qualifying serious adverse events in the study population during the specified assessment period. The exact numerator, denominator, and confidence interval are not reported in the posted statistical analyses.
6. Planned Analysis
The registry identifies the primary endpoint as the rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure. No formal statistical analyses are posted to ClinicalTrials.gov.
How this endpoint is typically analyzed
A safety rate of this type is generally summarized as a proportion: the number of participants experiencing at least one qualifying event divided by the relevant number of participants evaluated during the specified period. Because the endpoint concerns serious adverse events related to the device and/or procedure, the event definition and attribution rules are important components of the analysis.
A confidence interval for a proportion can be used to quantify statistical uncertainty around the observed rate. With a relatively small study such as an enrollment of 48, an exact binomial confidence interval can be particularly informative because the normal approximation may be unreliable when event counts are small or zero.
Observed rate
The primary descriptive quantity is the proportion of participants experiencing a qualifying serious adverse event through 6 months.
Uncertainty
A confidence interval around the proportion describes sampling uncertainty and should be interpreted alongside the observed number of events and the study size.
Attribution
The endpoint is restricted to serious adverse events related to the study device and/or study procedure, making attribution part of the endpoint definition.
Time frame
The registry specifies 6 months, so the rate is tied to the defined post-study procedure observation period.
7. Statistical Methods Explained
Why is this a rate rather than a hazard ratio?
The primary endpoint is defined as the rate of serious adverse events at a fixed 6-month time frame. A hazard ratio is a relative time-to-event measure comparing two groups or treatment conditions over time. BREATHE-1 has a single-group design and its registry-defined primary endpoint is a fixed-period safety rate, so a proportion is the more direct descriptive quantity.
What does the 6-month time frame mean?
The endpoint is explicitly assessed through 6 months post-study procedure. This creates a defined observation window for determining whether a serious adverse event related to the device and/or procedure occurred. Events outside that window would require separate rules if they were to be incorporated into another analysis.
Why does a single-group study not estimate a treatment effect?
A treatment effect in a randomized comparison is generally defined through the difference between treatment groups. BREATHE-1 has one intervention arm and no separate comparator arm in the registry design. Its primary safety endpoint therefore describes the occurrence of qualifying events within the treated study population rather than estimating a randomized treatment-versus-control contrast.
Why is the denominator important for a safety rate?
A rate cannot be interpreted from the event count alone. For example, the same number of events can represent very different proportions in studies with different numbers of participants. The analyzed denominator also matters if the number of participants actually evaluable at the relevant follow-up differs from enrollment.
Why is a confidence interval useful for a small safety study?
An observed proportion is only one estimate of the underlying event frequency. A confidence interval communicates how much statistical uncertainty surrounds that estimate. With 48 enrolled participants, the study size is modest, so the interval can remain relatively wide even when the observed event rate is measured precisely within the study.
Why is statistical significance not the central question here?
The primary endpoint is a safety rate in a single-group study rather than a randomized hypothesis test comparing two treatment groups. A descriptive estimate with an appropriate confidence interval is generally more informative for communicating the observed safety frequency than a p-value generated from an arbitrary comparison value.
8. Interpreting a Safety Rate
If the registry reported an observed primary-endpoint rate, that percentage would describe the proportion of the analyzed study population experiencing at least one serious adverse event that met the endpoint's relatedness definition during the 6-month post-study procedure period.
The rate would not establish how the Apreo Implant compares with another treatment or with no treatment because the registry describes a single-group design without a separate comparator arm. It also would not by itself establish that every serious adverse event in the study was caused by the device or procedure; the endpoint specifically concerns events considered related to the study device and/or study procedure.
A confidence interval would quantify uncertainty around the estimated safety rate. A wide interval would indicate that the observed proportion is compatible with a broad range of underlying event frequencies, while a narrower interval would indicate greater statistical precision.
If a p-value were reported for a prespecified statistical test, it would describe evidence against the corresponding null hypothesis under that test. It would not measure the magnitude of the SAE rate, the clinical importance of an event, or the probability that the device caused an event.
9. Statistical Interpretation of the Single-Group Design
The single-group structure is central to understanding the statistical evidence produced by BREATHE-1. With one intervention arm, the study can directly characterize what happened among participants who received the Apreo Implant, but the design does not create a randomized counterfactual group.
| Question | What the design supports |
|---|---|
| How often did qualifying serious adverse events occur? | A descriptive estimate of the rate can address this question within the defined 6-month observation period. |
| How precise is that estimated rate? | A confidence interval can quantify statistical uncertainty around the observed proportion. |
| Is the device safer than another treatment? | The single-group design does not provide a randomized between-group comparison for this question. |
| What is the relative treatment effect? | A treatment-effect contrast requires a comparator or another clearly defined reference framework. |
| What happened during the 6-month period? | The primary endpoint is specifically designed to summarize related serious adverse-event occurrence through 6 months post-study procedure. |
10. Safety Endpoint and Event Attribution
The primary endpoint is not simply all serious adverse events. Its registry definition specifically refers to serious adverse events related to the study device and/or study procedure. That distinction is statistically important because the numerator depends on an attribution rule as well as an event-severity rule.
Event severity
The endpoint is restricted to serious adverse events rather than all adverse events.
Device relationship
Events related to the study device are included in the endpoint definition.
Procedure relationship
Events related to the study procedure are also included.
Fixed assessment window
The registry specifies occurrence through 6 months post-study procedure.
This means that two safety summaries can differ even when they concern the same participants if they use different event definitions, attribution rules, or observation windows. For this endpoint, the reported definition should remain attached to any numerical estimate.
11. Sample Size and Statistical Precision
BREATHE-1 enrolled 48 participants. In a single-group safety study, this sample size determines how precisely a proportion can be estimated. The smaller the number of participants, the greater the potential impact of each individual event on the observed percentage.
The percentage changes discretely as individual participants enter or leave the numerator. Consequently, a small study can provide useful descriptive safety information while still producing substantial statistical uncertainty around the underlying event frequency.
The enrollment number alone does not establish the precision of the final primary-endpoint estimate. The analyzed denominator, number of qualifying events, and confidence-interval method would all be needed to describe the statistical uncertainty of the completed analysis.
12. What the Registry Reports About the Study Structure
| Design element | Registry description | Statistical implication |
|---|---|---|
| Allocation | NA | No randomized allocation comparison is specified. |
| Design model | Single-group | The primary safety analysis is within one intervention group. |
| Masking | None | The study is not described as masked. |
| Primary purpose | Treatment | The study evaluates the intervention in a treatment setting. |
| Number of arms | 1 | No separate comparator arm is specified. |
| Phase | NA | No conventional phase designation is reported in the registry data. |
13. What Is and Is Not Available for Statistical Interpretation
The registry identifies one primary endpoint and its assessment period, but no posted statistical analyses accompany that endpoint. This creates an important distinction between the study's registered statistical question and its posted numerical results.
| Item | Registry status |
|---|---|
| Primary endpoint | Reported |
| Primary endpoint time frame | Reported as 6 Months |
| Endpoint definition | Reported |
| Statistical analysis for the primary endpoint | No posted statistical analysis |
| Primary endpoint event count | Not reported in the posted statistical analyses |
| Primary endpoint rate | Not reported in the posted statistical analyses |
| Confidence interval | Not reported in the posted statistical analyses |
| P-value | Not reported in the posted statistical analyses |
14. Limitations
- No randomized comparator: the single-group design does not provide a randomized control group against which the observed safety rate can be directly compared.
- Modest enrollment: 48 participants limits the statistical precision available for estimating a safety proportion, particularly when qualifying events are uncommon.
- Event attribution: the primary endpoint depends on determining whether serious adverse events are related to the study device and/or study procedure.
- Fixed follow-up window: the primary endpoint is defined through 6 months post-study procedure, so it summarizes safety within that specified period rather than all possible later events.
- No posted statistical analysis: the ClinicalTrials.gov record does not provide a numerical analysis of the registered primary endpoint.
- Single-group interpretation: an observed event rate describes the study population and does not by itself establish a comparative treatment effect.
- Generalizability: a first-in-human study population may not represent every patient with emphysema or COPD who might subsequently receive the device.
15. Why This Trial Matters Statistically
BREATHE-1 is a useful statistical teaching case because it illustrates how early device studies can ask a focused safety question without using a randomized comparator.
| Statistical concept | How it appears in BREATHE-1 |
|---|---|
| Single-group design | One intervention arm is specified. |
| Safety endpoint | The primary endpoint concerns serious adverse events related to the device and/or study procedure. |
| Proportion / rate | The endpoint is expressed as the rate of occurrence through a specified period. |
| Fixed follow-up | The primary endpoint uses a 6-month time frame. |
| Confidence interval | An interval around a safety proportion can communicate statistical precision. |
| Event attribution | Relatedness to the device and/or procedure is part of the endpoint definition. |
| Denominator selection | The interpretation of a rate depends on which participants are included in the analyzed denominator. |
| Comparative inference | A single-group study does not provide the randomized contrast required for a conventional treatment-effect estimate. |
16. Clinical Interpretation vs Statistical Interpretation
Statistical interpretation
The primary statistical quantity is a 6-month rate of serious adverse events related to the study device and/or study procedure. Its interpretation depends on the observed event count, analysis denominator, and statistical uncertainty around the resulting proportion.
Clinical interpretation
The study is intended to characterize safety of the Apreo Implant in a first-in-human setting. The clinical meaning of the safety findings depends on the nature and severity of qualifying events as well as their relationship to the device and procedure.
These two perspectives should remain distinct. Statistical precision describes how confidently the study estimates an event frequency; clinical interpretation considers what the observed events mean in the context of the device and procedure.
17. Sources
- ClinicalTrials.gov: BREATHE-1, NCT05854550.
- PubMed: PubMed record associated with BREATHE-1.
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18. Record Summary
BREATHE-1 is a completed first-in-human, single-group study of the Apreo Implant in emphysema or COPD. The study enrolled 48 participants and used one unmasked intervention arm. Its registered primary endpoint is the Rate of Serious Adverse Events (SAE) at 6 Months, defined as the rate of occurrence of serious adverse events related to the study device and/or study procedure through 6 months post-study procedure.
Statistically, the central feature of BREATHE-1 is the interpretation of a fixed-period safety proportion in a single-group design. The observed rate, its confidence interval, the event count, and the analysis denominator would provide the quantitative description of the primary endpoint. The registry identifies the endpoint and its 6-month time frame, but no formal statistical analyses are posted on ClinicalTrials.gov.