Trial Outcomes & Findings for Urease Breath Test for Rapid Characterization of Pneumonia (NCT NCT03100760)

Subjects were recruited from the emergency departments of University of New Mexico Health Sciences Center and Henry Ford Hospital. Eligible participants presented with clinical suspicion for community-acquired pneumonia and were screened for outpatient (Cohort A) or inpatient (Cohort B) treatment enrollment.

All subjects provided written informed consent prior to participation. Subjects were screened for eligibility, including medical history, vital signs, and ability to perform breath sampling. No randomization was performed; subjects were assigned to outpatient or inpatient cohorts based on clinical treatment plan.

Race data were collected for inpatient participants but not outpatient participants.

Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.

Death, disability, incapacitation, escalation of level of care, prolongation of hospitalization, birth defect, or intervention to prevent the above.

Any adverse event for which there is a reasonable possibility that the adverse event was caused by the study drug.

Any Suspected Adverse Reaction that is determined to be serious, based on the outcomes of a Serious Adverse Event; i.e. death, life-threatening, causes or prolongs inpatient hospitalization, causes a persistent of significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital abnormality/birth defect.

We recorded change in 13CO2/12CO2 ratio (delta over baseline or ΔOB, in units of ‰) between pre- and post-nebulization samples

We recorded change in 13CO2/12CO2 ratio (delta over baseline or ΔOB, in units of ‰) between pre- and post-nebulization samples and compared with subject's causative pathogen based upon sputum or blood culture results

Number of participants With ¹³CO₂/¹²CO₂ Ratio Correlated (ρ \> 0.75) to CURB-65 Score in Urease-Positive Pneumonia

Number of Participants With ¹³CO₂/¹²CO₂ Ratio Correlated (ρ \> 0.75) to Pneumonia Severity Index in Urease-Positive Pneumonia.

This exploratory outcome was designed to assess whether the ¹³C-urea breath test (Δ¹³CO₂) is associated with the presence of urease-producing pathogens. Correlation between exhaled ¹³CO₂ levels and pathogen abundance (based on RNAseq bacterial counts) was to be evaluated using Spearman's correlation, with a pre-defined significance threshold of ρ \> 0.75.

This exploratory outcome was designed to assess the specificity of the ¹³C-urea breath test (Δ¹³CO₂) for detecting urease-producing pathogens. Specificity was defined as the proportion of participants without urease-producing pathogens (based on RNAseq bacterial profiles) who also did not meet the predefined breath test threshold. The planned analysis used Spearman correlation (ρ) between ¹³CO₂ enrichment and bacterial abundance, with ρ \< 0.75 indicating a negative test result.

This exploratory outcome measured the number of participants who met the criteria for positive predictive value of the ¹³C-urea breath test. A participant was considered to meet the PPV criterion if they had a positive breath test result (Spearman ρ \> 0.75 between Δ¹³CO₂ and bacterial abundance) and also had RNAseq-confirmed presence of at least one urease-producing pathogen.

This exploratory outcome was designed to evaluate the number of participants meeting the negative predictive value (NPV) criterion of the ¹³C-urea breath test for detecting urease-producing pathogens. A participant was considered to meet the NPV criterion if they had a negative breath test result defined as a Spearman correlation coefficient (ρ) ≤ 0.75 between Δ¹³CO₂ and bacterial abundance and RNAseq-confirmed absence of urease-producing pathogens.