A Phase 1, Open-label, Evaluation of a 13C-urea Breath Test for the Detection of Urease-producing Bacteria in Patients Diagnosed With Pneumonia in the Emergency Department
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of New Mexico
- Enrollment
- 75
- Locations
- 2
- Primary Endpoint
- Adverse Events
Study Overview
Brief Summary
This is a Phase 1, open label, evaluation of a 13C-urea breath test for the detection of urease-producing bacteria in patient with pneumonia in the emergency department.
Detailed Description
This is a Phase 1, open-label evaluation of an inhaled 13C-urea breath test in the identification of urease positive bacteria in patients diagnosed with pneumonia in the emergency department (ED). This study will enroll up to 75 adult male and female subjects in two cohorts. Adult subjects will be screened for participation in two dosing cohorts to be enrolled sequentially. Cohort A will enroll 15 subjects presenting to the ED with clinical concern for pneumonia and plan for outpatient treatment. Following enrollment and review of the safety of dosing in Cohort A, subjects receiving a diagnosis of pneumonia in the ED that are planned for admission will be screened for enrollment in Cohort B. Eligible subjects will provide informed consent, medical history, and samples for laboratory testing (including pregnancy testing for females of childbearing potential) during screening. Subjects will be evaluated for their CURB-65 Pneumonia Severity Score, and Community-Acquired Pneumonia Severity Index (PSI) where required data are available.
Prior to breath test administration, subjects will provide a sputum sample for bacterial culture; sample may be induced, or collected as part of initial ED workup if appropriate culture has been ordered. Subjects will undergo breath test with collection of baseline breath samples (up to 6), followed by complete nebulization of 13C-urea solution. Immediately following the end of nebulization, breath collection bag samples will be collected at up to 6 time points with at least 1 minute intervals within 10 minutes post-nebulization. Exhaled breath bags will be centrally processed to determine the change in exhaled 13CO2 levels. Vital signs, including resting blood pressure, resting pulse, respiratory rate, peripheral oxygen saturation, and temperature will be collected prior to, and following completion of, nebulization treatment. In the event of bronchospasm, during or following nebulization, albuterol rescue will be available for treatment at the discretion of the investigator.
Once required tests are complete, the subject will be treated/followed according to standard institutional protocol/practice. The subjects' clinical course will be followed for at least 24 hours, where possible, to document the final diagnosis and outcome.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- Single (Care Provider)
Masking Description
Care Providers will not be provided with the results of the breath test, and will treat patients according to the current standards of care
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Cohort A Only: be a man or woman age 18-65, inclusive, with suspected bacterial pneumonia on presentation to the ED based on clinical signs and symptoms AND be planned for outpatient treatment
- •Cohort B Only: be a man or woman age 18-85, inclusive, with a diagnosis of suspected bacterial pneumonia in the ED based on findings of a positive chest x-ray and clinical signs and symptoms AND be planned for admission to the hospital ward/floor
- •be capable of providing a spontaneous or induced sputum sample for analysis
- •be capable of completing the breath test according to the clinical judgement of the investigator
- •be able to understand the study procedures, agree to participate in the study program, and voluntarily provide written informed consent
Exclusion Criteria
- •have a known allergy to urea or any excipient in the nebulized solution
- •be pregnant or have a positive urine pregnancy test
- •have evidence of active oral infection, such as abscess or dense exudate, that requires antibiotic therapy
- •have known diagnosis of cystic fibrosis or bronchiectasis
- •have a known or suspected acute asthma exacerbation on presentation to the ED
- •have received treatment with oral or intravenous (IV) antibiotics in the preceding 2 days prior to screening, unless antibiotic failure is suspected
- •have received treatment in the ED with oral or IV antibiotics greater than 4 hours prior to breath test
- •have an acute illness or other condition that, as determined by the investigator, would preclude participation in the study
Outcomes
Primary Outcomes
Adverse Events
Time Frame: Within 24-48 hours of breath test
Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Serious Adverse Events
Time Frame: Within 24-48 hours of breath test
Death, disability, incapacitation, escalation of level of care, prolongation of hospitalization, birth defect, or intervention to prevent the above.
Serious Suspected Adverse Reaction
Time Frame: Within 24-48 hours of breath test
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.
Suspected Adverse Reaction
Time Frame: Within 24-48 hours of breath test
Any adverse event for which there is a reasonable possibility that the adverse event was caused by the study drug.
Secondary Outcomes
- Exhaled 13CO2 Concentration(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants With ¹³CO₂/¹²CO₂ Ratio Correlated (ρ > 0.75) to Bacterial RNAseq Counts(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants With ¹³CO₂/¹²CO₂ Ratio Correlated (ρ > 0.75) to CURB-65 Score in Urease-Positive Pneumonia(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants With ¹³CO₂/¹²CO₂ Ratio Correlated (ρ > 0.75) to Pneumonia Severity Index in Urease-Positive Pneumonia.(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants Meeting Sensitivity Criterion of ¹³C-Urea Breath Test for Urease-Producing Pathogens(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants Meeting Specificity Criterion of ¹³C-Urea Breath Test for Urease-Producing Pathogens(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants With Breath Test Positive and Confirmed Urease-Producing Pathogen (PPV Criterion)(Collected at 6 minutes after nebulization and measured within 7 days of collection)
- Number of Participants Meeting Negative Predictive Value Criterion of ¹³C-Urea Breath Test for Urease-Producing Pathogens(Collected at 6 minutes after nebulization and measured within 7 days of collection)
Investigators
Justin T Baca
Assistant Professor of Emergency Medicine
University of New Mexico