CTTI Risk Factors for HABP/VABP Study

Study Overview
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Brief Summary
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The purpose of this study is to better define the intensive care unit population at highest risk for developing Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP).

Detailed Description
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This is a prospective, multi-center, observational study of adult patients (≥18 years old) admitted to ICUs. Generally, all patients admitted to the ICU for any indication will be considered at risk for developing HABP/VABP. A subset of the at-risk patients treated with select respiratory modalities for at least 12 hours will be considered high risk for the development of HABP/VABP, will have baseline data collected, and will be screened daily for antibiotic treatment for suspected pneumonia. Patients not meeting high-risk criteria, other-ICU patients, will be screened twice weekly for antibiotic treatment for suspected pneumonia. Once a high-risk subject or other-ICU patient is treated with antibiotics for either a lower respiratory tract infection (LRTI) or undifferentiated sepsis, additional clinical information will be recorded from the subject's medical record. All subjects treated with antibiotics for either indication will subsequently be screened for the development of pneumonia, as defined by the FDA draft guidance document for drug development in HABP/VABP. Subjects who meet the FDA draft guidance definition of pneumonia will have vitals and physiologic data collected and will be followed for 4 days after pneumonia is diagnosed to capture the results of any microbiologic testing and changes to initial antibiotic therapy.

Official Title
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Prospective Observational Study of the Risk Factors for Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP)

Conditions
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Pneumonia, Ventilator-Associated, Pneumonia, Bacterial, Pneumonia, Hospital-Acquired

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Adult arm => 18 years old): Admission to participating ICU Hospitalized for >48 hours or admitted <7 days after discharge from an inpatient acute or chronic care facility High-Risk Inclusion (Adult arm => 18 years old): Treated with one or more of the following respiratory modalities for at least 12 hours, either currently or within the prior 7 days: Invasive mechanical ventilation Noninvasive ventilation (BiPAP or CPAP for any indication other than obstructive sleep apnea) High-flow, supplemental oxygen therapy via nasal cannula. Only include systems that using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM. High flow supplemental oxygen therapy delivering at least 50% FiO2 via aerosol facemask or tracheostomy collar (mask). Only include systems using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM. Supplemental oxygen therapy delivered via either partial or non-rebreather face mask Other-ICU Inclusion(Adult arm => 18 years old): All patients who meet ICU and time-frame eligibility criteria, but do not fulfill high-risk criteria, and are receiving an antibiotic for treatment of LRTI or undifferentiated sepsis. Exclusion Criteria(Adult arm => 18 years old): Age <18 years old Pregnancy (current) or breastfeeding Lung cancer or another malignancy metastatic to the lungs (currently receiving treatment) Patient previously enrolled and treated for suspected HABP or VABP (More than CRF Part 1 was previously completed) Patient is on comfort measures (e.g. would not receive antibiotics) Inclusion Criteria (Pediatric Arm: < 18 years old) < 18 years old Admission to participating ICU or intermediate care unit Hospitalized for >48 hours or admitted <7 days after discharge from an inpatient acute or chronic care facility Note: Children and infants with pulmonary and cardiac anomalies are eligible to participate. High-Risk Inclusion (Pediatric Arm: < 18 years old) Subjects ≥120 days old and <18 years old: Currently treated with one or more of the following respiratory modalities for at least 24 hours: Invasive mechanical ventilation via endotracheal intubation New initiation of mechanical ventilation, BiPAP or CPAP via tracheostomy Noninvasive ventilation (BiPAP or CPAP for any indication other than obstructive sleep apnea) High-flow, supplemental oxygen therapy delivering at least 1.5LMP with 100% FiO2 via nasal cannula when delivered using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM High flow supplemental oxygen therapy delivering at least 50% FiO2 via aerosol facemask or tracheostomy collar (mask) when delivered using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM Supplemental oxygen therapy delivered via either partial or non-rebreather face mask Subjects <120 days old: Currently treated with mechanical ventilation via endotracheal intubation for at least 5 days Standard-Risk Inclusion (Pediatric Arm: < 18 years old) All patients who meet pediatric eligibility criteria, but do not fulfill high-risk criteria, and are receiving an antibiotic for treatment of LRTI or undifferentiated sepsis. Exclusion Criteria (Pediatric Arm: < 18 years old) Known pregnancy (current) or breastfeeding Lung cancer or another malignancy metastatic to the lungs (currently receiving treatment) Patient previously enrolled and treated for suspected HABP or VABP (More than Pediatric CRF Part 1 was previously completed) Patient is on comfort measures (e.g. would not receive antibiotics)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High-Risk (Adult =>18 years old)<br>Treated with one or more of the following respiratory modalities for at least 12 continuous hours, either currently or within the prior 7 days: Invasive mechanical ventilation Noninvasive ventilation (BiPAP or CPAP for any indication other than obstructive sleep apnea) High-flow, supplemental oxygen therapy via nasal cannula. Only include systems that using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM. High flow supplemental oxygen therapy delivering at least 50% FiO2 via aerosol facemask or tracheostomy collar (mask). Only include systems using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM. Supplemental oxygen therapy delivered via either partial or non-rebreather face mask | |
| Other-ICU/Standard Risk<br>Patients do not fulfill high-risk criteria, but, are receiving an antibiotic for treatment of lower respiratory tract infection or undifferentiated sepsis. | |
| High-Risk (Pediatric ≥120 days old and <18 years old)<br>Currently treated with one or more of the following respiratory modalities for at least 24 hours: Invasive mechanical ventilation via endotracheal intubation New initiation of mechanical ventilation, BiPAP or CPAP via tracheostomy Noninvasive ventilation (BiPAP or CPAP for any indication other than obstructive sleep apnea) High-flow, supplemental oxygen therapy delivering at least 1.5LMP with 100% FiO2 via nasal cannula when delivered using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM High flow supplemental oxygen therapy delivering at least 50% FiO2 via aerosol facemask or tracheostomy collar (mask) when delivered using an air/oxygen blender capable of delivering a precise FiO2 level, not just a flow in LPM Supplemental oxygen therapy delivered via either partial or non-rebreather face mask | |
| High-Risk (Pediatric <120 days old)<br>Currently treated with mechanical ventilation via endotracheal intubation for at least 5 days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of HABP/VABP | Estimate the rate of HABP/VABP diagnosis in ICU subjects who meet the predetermined high-risk criteria. | Through completion of the study, up to 12 months | 
| Eligibility for typical antibacterial clinical trial | Estimate the proportion of ICU subjects diagnosed with HABP/VABP who would be eligible for enrollment in a clinical trial of antibacterial therapy for HABP/VABP per FDA draft guidance on HABP/VABP | Through completion of the study, up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In enrolled subjects, what factors are associated with the development of hospital acquired or ventilator associated pneumonia. | Assess the risk factors, comorbid medical illnesses, and treatment exposures associated with the development of HABP/VABP in ICU subjects at high-risk for developing pneumonia using a logistic regression model with age, sex, height (cm), weight (kg), ICU type, admission source, hospital length of stay at the time of screening (calendar days), ICU length of stay at the time of screening, ICU admission diagnosis, aspiration risk, medical history, type and duration of ventilation, enteral nutrition, medications, and other therapies of interest as factors | Through completion of the study, up to 12 months |