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 Safety Study of Inhaled Carbon Monoxide to Treat Pneumonia and Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS) (NCT04870125), a randomized phase 1 study. The primary outcome is Primary Safety Outcome: Number of Pre-specified Administration-related Adverse Events (AEs)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04870125 |
| Phase | Phase 1 |
| Condition | Acute Respiratory Distress Syndrome, Sepsis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Brigham and Women's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Adults with sepsis-induced acute respiratory distress syndrome (ARDS) were the intended study population. The registry lists acute respiratory distress syndrome and sepsis as conditions. The record says all subjects were analyzed for safety measures, but it does not give further eligibility details in the information available for this analysis.
Intervention
The intervention was inhaled carbon monoxide (iCO), with a personalized dose determined by a Coburn-Forster-Kane equation. The stated dose range was 200-500 ppm, intended to achieve a carboxyhemoglobin (COHb) level of 6-8%. Treatment was given for up to 90 minutes daily for 3 days.
Comparator
The comparison group received inhaled medical air for up to 90 minutes daily for 3 days. The study is described as placebo-controlled in its summary. The registry classifies masking as double, while its summary describes the trial as partially double-blind.
Primary question
The primary question was whether personalized inhaled carbon monoxide dosing was associated with prespecified administration-related adverse events and spontaneously reported adverse events through study day 7. The trial also planned to examine biologic readouts and listed lung injury, oxygenation, organ failure, and days free of ventilation, intensive care, or hospitalization among secondary outcomes. Those additional outcomes do not change the primary safety focus.
3. Trial Design
This was a Phase Ib, randomized, parallel-group trial sponsored by Brigham and Women's Hospital. The registry identifies the allocation as randomized and masking as double. The brief summary calls the study multicenter, randomized, partially double-blind, and placebo-controlled. These descriptions are reproduced as recorded; the registry information does not explain the difference in masking terminology.
The trial compared inhaled carbon monoxide with inhaled medical air. In the carbon monoxide group, the dose was personalized using a Coburn-Forster-Kane equation, with 200-500 ppm specified to target a COHb level of 6-8%. Both assigned treatments were administered for up to 90 minutes daily for 3 days. The stated purpose was to evaluate the safety and accuracy of the personalized dosing algorithm and examine biologic readouts in patients with sepsis-induced ARDS.
Enrollment was 5. The study started on 2023-12-06, had a primary completion date of 2024-10-25, and is listed as terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the trial ended or what affected recruitment or follow-up. The posted record lists 21 outcome measures and 0 analysis entries. That distinction matters: outcome measures describe what was planned or collected, whereas analysis entries would provide statistical results. The presence of a planned outcome does not establish that its results were analyzed or posted.
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.
Before assignment: After consent. Subjects were randomized to either placebo or inhaled CO. Study procedures started the following day after randomization.
Overall Study
| Stage | Inhaled Carbon Monoxide | Medical Air |
|---|---|---|
| STARTED | 2 | 2 |
| COMPLETED | 2 | 2 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All subjects were analyzed for safety measures.
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.
| Characteristic | Unit | Inhaled Carbon Monoxide | Medical Air | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 2 | 4 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 1 | 3 |
| Age, Categorical: >=65 years | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 2 | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Baseline Critical Illness Category: ARDS with Sepsis | Participants | 1 | 2 | 3 |
| Baseline Critical Illness Category: Pneumonia with sepsis, without ARDS | Participants | 1 | 0 | 1 |
| Baseline Critical Illness Category: Pneumonia without ARDS or sepsis | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Primary Safety Outcome: Number of Pre-specified Administration-related Adverse Events (AEs)., measured over 7 days.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled as the number of participants with prespecified administration-related adverse events. Its description defines safety using the incidence of these events, together with spontaneously reported adverse events, through study day 7. The prespecified events include acute myocardial infarction and acute cerebrovascular accident within 48 hours of study drug administration; new atrial or ventricular arrhythmia requiring DC cardioversion within 48 hours; specified increases in oxygenation requirements within 6 hours; an increase in COHb of at least 10%; and an increase in lactate of at least 2 mmol/L within 6 hours.
A safety endpoint is appropriate to the stated Phase Ib purpose: it organizes monitoring around possible harms during and after administration of an investigational dosing approach. Counting participants with an event can make the frequency of observed safety events easier to interpret than reporting event narratives alone. However, a count does not by itself establish whether an event was caused by treatment. Clinical context, timing, severity, event definitions, and the comparison between randomized groups all matter.
The registry record does not provide a single primary endpoint comparison or a numerical estimate for this outcome. It identifies the measure and its timeframe, but the posted analysis does not reduce the outcome to one reported comparison. Therefore, the endpoint definition can be described, but its treatment-group effect and precision cannot be quantified from the available record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record specifies a primary safety outcome but does not post a single analysis of it. The primary measure concerns prespecified administration-related adverse events and spontaneously reported adverse events through study day 7. The record gives the event definitions and says all subjects were analyzed for safety measures, but it does not provide a primary endpoint estimate, confidence interval, or statistical comparison. As a result, the primary safety question cannot be answered quantitatively from the posted results.
The available serious adverse event summary lists one participant with a serious event in each group, with 2 at risk in each. It lists no other adverse events in either group among those at risk, and lists deaths of 0 in the inhaled carbon monoxide group and 1 in the medical air group. These are descriptive counts from a very small study. They should not be treated as a reliable comparison of underlying safety rates or as evidence that one treatment caused or prevented an event. The posted information does not give a causal assessment or enough detail to determine the relationship of each event to treatment.
The serious event terms listed are Respiratory failure, Atrial fibrilation, and Death NOS, each reported as 50.0%. The registry record does not explain the denominator or the construction of these term percentages in the information. They should therefore be read as descriptive entries, not as participant-level risks or as a basis for comparing groups. Serious event terms may describe different aspects of the same clinical course; the record does not clarify whether terms overlap.
Enrollment was 5, and the study is listed as terminated. The small enrollment limits how much can be learned from sparse event counts: uncommon harms may not appear, and estimates based on few observations would be imprecise. No uncertainty interval is posted for the primary outcome. In general, a confidence interval describes the range of effect values reasonably compatible with the data and analysis; its absence means the precision of the primary comparison cannot be assessed from this record.
The registry lists secondary measures covering lung injury score, oxygenation, dead space, organ failure, and ventilator-free, ICU-free, and hospital-free days. Their inclusion does not establish that numerical results are available. The record lists 0 analysis entries, and no numerical results for those secondary measures are included in the information. Consequently, interpretation should remain limited to the stated design and the descriptive adverse event counts, without drawing conclusions about physiologic response, clinical benefit, or comparative safety.
9. Statistical Methods Explained
Randomization is a way to assign participants to study groups using a chance-based process. In general, it helps reduce systematic differences between groups at the start of a trial, although it does not guarantee balance in a very small study. This record classifies allocation as randomized and the model as parallel: the comparison is between groups assigned to different treatments, rather than a crossover in which participants receive treatments in sequence. The record does not report the sequence-generation method, allocation concealment, or whether assignment was stratified.
What does masking mean in this record?
Masking means that some people involved in a trial are kept unaware of assigned treatment, which can reduce the influence of expectations on care, measurement, or reporting. The registry classification says double masking, while the brief summary says partially double-blind. The record does not explain which participants, clinicians, assessors, or other personnel were masked, or how masking was maintained. Those details are not reported in the registry record. The terms should not be treated as interchangeable descriptions of a fully documented masking procedure.
What does a participant count measure?
The primary outcome is expressed as a count of participants with an event. This is a binary outcome at the participant level: a person either meets the event definition or does not, according to the analysis rules. This differs from an event count, because one participant may experience more than one event. The endpoint description combines prespecified administration-related events with spontaneously reported adverse events through study day 7. The record does not explain how multiple events in one participant would be handled in a primary analysis, or whether event severity and attribution would be incorporated beyond the stated definitions.
For a binary outcome, an analysis might report counts and proportions in each group and a contrast between groups. General statistical practice may also use an uncertainty interval to show how imprecisely the contrast is estimated. Those are general concepts, not a description of the analysis performed in this trial. The registry record does not post a primary endpoint estimate, interval, or test. With sparse counts, conventional approximations can be unreliable; however, no specific inferential method is reported, so it would be inappropriate to assign one to this study.
Why does sparse information affect interpretation?
When only a few participants are enrolled and few events are recorded, each observation can have a substantial influence on a treatment-group summary. Estimates may vary considerably with the outcome of an individual participant. In general, wider uncertainty is expected when information is limited, but the precision of this trial's primary effect cannot be stated without a reported estimate and interval. A non-significant result, if one had been reported, would not by itself establish that treatments are equivalent or that an important difference is absent. No such test result is included in the record.
The serious adverse event summary separately reports participants at risk, participants affected, other adverse events, and deaths by group. These categories are not necessarily interchangeable with the prespecified primary endpoint. The summary does not establish whether each serious event met a primary endpoint definition, whether events were treatment-related, or how the death relates to the reported serious terms. Those links are not reported in the registry record. Descriptive safety counts are useful for transparency, but they do not replace the defined primary endpoint analysis.
What can planning calculations show?
General sample-size planning asks how much information a future study would need to detect a specified effect under stated assumptions. The record's planning assumptions describe a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; they also say the effect to detect is a stated fraction of the observed effect. Such planning calculations are conditional illustrations, not observed power and not the trial's original design justification. The registry record does not report the protocol's sample-size justification or an interim-analysis plan. A planned sample size cannot repair the limits of the observed evidence, and an estimate based on observed effects should be interpreted cautiously when the underlying data are sparse.
The registry lists 21 outcome measures and 0 analysis entries. A measure's presence in a registry establishes that it was recorded as an outcome, not that it was analyzed, that all measurements were complete, or that results were made available. The analysis methods, handling of missing observations, outcome-specific populations, and any adjustment for multiple comparisons are not reported in the registry record. These details matter because statistical conclusions depend not only on outcome definitions, but also on who was included, how incomplete data were treated, and which analyses were selected.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 21 outcome measures, including one primary safety outcome and secondary measures of lung injury, oxygenation, organ failure, and days free of ventilation, intensive care, or hospitalization. When a study evaluates multiple outcomes, the chance of obtaining at least one apparently unusual result can increase if each is tested independently. General approaches to multiplicity include designating a primary outcome in advance, adjusting significance thresholds, or treating additional outcomes as exploratory. The registry record does not report whether any multiplicity adjustment or testing hierarchy was used.
The primary outcome is defined through study day 7, while secondary outcomes include specified time points extending to Day 60. Repeated measurements can raise additional analysis questions, such as how observations over time are combined and how incomplete follow-up is handled. The record does not report the statistical methods for repeated measures, missing data, or outcome-specific analysis populations. It says all subjects were analyzed for safety measures, but does not give further detail about that population or describe populations used for other outcomes.
The registry lists 0 analysis entries. Thus, the record does not offer enough information to assess whether the planned outcomes were analyzed as specified, whether all outcomes were reported, or how missing observations might affect the results. These are not grounds to infer that analyses were omitted or that data were missing; they are aspects that are not reported in the registry record. Without analysis details and numerical results, the multiplicity and missing-data implications cannot be evaluated for this trial.
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 |
|---|---|---|---|
| Inhaled Carbon Monoxide | 1 | 2 | 50.0% |
| Medical Air | 1 | 2 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Inhaled Carbon Monoxide | 0 of 2 |
| Medical Air | 1 of 2 |
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 |
|---|---|
| Inhaled Carbon Monoxide | 0 of 2 |
| Medical Air | 0 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Inhaled Carbon Monoxide | Medical Air |
|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 2 | 0 of 2 |
| Atrial fibrilation | Cardiac disorders | 0 of 2 | 1 of 2 |
| Death NOS | General disorders | 0 of 2 | 1 of 2 |
Serious events with the highest arm-level rate: respiratory failure (50.0%), atrial fibrilation (50.0%), death nos (50.0%).
The serious adverse event listing reports 2 at risk and 1 affected in the inhaled carbon monoxide group, and 2 at risk and 1 affected in the medical air group. The listing reports 0 other adverse events among 2 at risk in each group. Deaths are listed as 0 for inhaled carbon monoxide and 1 for medical air. These counts are descriptive and should be read as recorded, not as evidence of a treatment effect. With enrollment of 5 and sparse events, they provide limited information about how often harms might occur beyond this trial.
The listed serious terms are Respiratory failure, Atrial fibrilation, and Death NOS, each with 50.0%. The registry record does not explain the denominator for those percentages or whether the terms refer to separate participants or overlapping event descriptions. The terms should not be added together or interpreted as separate participant-level probabilities. Nor does the listing establish that an event was caused by the assigned treatment. The record does not provide event-level timing, attribution, or a direct mapping between these terms and the primary endpoint criteria.
12. What the Result Does, and Does Not, Mean
The posted record describes a randomized Phase Ib comparison of personalized inhaled carbon monoxide with inhaled medical air in sepsis-induced ARDS. Its primary focus was safety: prespecified administration-related adverse events and spontaneously reported adverse events through study day 7. The record also describes the intended dosing approach and lists secondary physiologic and clinical outcomes. These details clarify what the trial set out to evaluate, but they are not themselves evidence of a treatment effect.
The serious adverse event listing contains sparse descriptive counts, including one serious event in each group and one death listed in the medical air group. Without a posted primary endpoint analysis, uncertainty estimates, and fuller event-level information, those counts cannot establish comparative safety, causality, or absence of risk. In particular, no event count in a small study can show that uncommon harms do not occur. The registry record does not report a reason for the terminated status, so it should not be used to infer the reason the study ended.
The record does not provide numerical results for the listed secondary outcomes in the information available for this analysis. Therefore, it cannot support conclusions about changes in lung injury score, oxygenation, organ failure, or days free of ventilation, intensive care, or hospitalization. Listing these measures does not demonstrate improvement or worsening.
In general, results from an early-phase study can help describe feasibility, dosing, and observed safety, but their interpretation depends on the amount and completeness of data and on the analysis. Here, enrollment was 5 and the registry lists 0 analysis entries. The posted information is consequently insufficient to quantify the primary treatment contrast or its precision. This is a statement about what the record reports, not a medical recommendation or a judgment about the treatment's value.
13. Why This Trial Matters Statistically
This trial raises statistical questions that are especially important in early-phase safety research. The dosing strategy aimed to use a Coburn-Forster-Kane equation to personalize inhaled carbon monoxide and target a COHb level of 6-8%. Evaluating such an approach involves more than recording whether an adverse event occurred: interpretation also depends on whether the target was reached, how safely dosing proceeded, and how observations are summarized. The registry describes the intended algorithm and target but does not post a numerical analysis of its accuracy.
The randomized comparison with medical air provides a framework for descriptive contrasts, but the small enrollment and sparse adverse event counts sharply limit what such contrasts can establish. Randomization helps address systematic differences in expectation, yet chance variation remains substantial when information is limited. The counts cannot reliably characterize uncommon events or establish that observed events were caused by, or unrelated to, a study treatment.
The endpoint combines specified acute events with spontaneously reported adverse events. This reflects the practical breadth of safety monitoring, while also making the analysis rules important: participant-level counting, event-level counting, timing, and attribution can lead to different summaries. The record states the principal event definitions but does not report the detailed analysis plan or a numerical primary comparison.
Finally, the record lists many outcome measures but no analysis entries. This distinction is statistically consequential. Planned outcomes can inform readers about the questions investigators intended to study, but results and uncertainty are needed to assess what the data show. Clear reporting of outcome-specific methods, missingness, and multiplicity would help readers separate the primary safety question from exploratory signals. The available record permits a description of the trial's aim and limited safety counts, but not a precise estimate of treatment differences.
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.
Several trial-specific limitations constrain interpretation. Enrollment was 5, and the study is listed as terminated. These registry entries indicate that the available trial record contains a small body of information, but the reason for termination is not reported in the registry record. It would be speculative to attribute termination to safety, recruitment, logistics, or any other cause.
The primary endpoint is described in detail, but the posted results do not provide a single analysis of it. The record lists 0 analysis entries, so there is no reported primary effect estimate or uncertainty interval to assess. Although the safety listing gives counts by group, the record does not establish which listed events met the primary endpoint definition, how events were attributed, or how repeated events in an individual were handled.
The outcome list spans safety, physiologic measures, organ failure, and outcomes assessed over different periods. The statistical analysis plan, multiplicity approach, missing-data handling, and analysis populations beyond the statement about safety are not reported in the registry record. Without these details, it is not possible to assess whether the planned outcomes were analyzed consistently or how incomplete follow-up might influence results.
The registry describes the trial as double masked in its design classification and partially double-blind in the summary, without explaining who was masked. It also does not provide further information about the randomization process. These reporting gaps limit assessment of the protections against bias. Finally, adverse event term percentages are listed without an explanation of their denominator or relationship to participants, and the record does not clarify overlap among terms. They should be interpreted cautiously as descriptive entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Study of Inhaled Carbon Monoxide to Treat Pneumonia and Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS) — NCT04870125.
- Registry record last updated 2026-05-26; status last verified 2026-05.
- Results first posted 2026-05-26.
- 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
NCT04870125 is a randomized, parallel Phase Ib trial sponsored by Brigham and Women's Hospital. It compared personalized inhaled carbon monoxide with inhaled medical air in sepsis-induced ARDS. The stated carbon monoxide dosing approach used a Coburn-Forster-Kane equation, with 200-500 ppm intended to achieve a COHb level of 6-8%, for up to 90 minutes daily for 3 days. The primary outcome concerned prespecified administration-related adverse events and spontaneously reported adverse events through study day 7.
Enrollment was 5. The study started on 2023-12-06, had a primary completion date of 2024-10-25, and is listed as terminated. The record lists 21 outcome measures and 0 analysis entries. Its serious adverse event summary reports sparse counts by group, but no single primary outcome comparison or uncertainty estimate. The reason for termination, detailed statistical plan, and numerical results for the listed secondary measures are not reported in the registry record.