Clinical trial NCT02689531: CTTI Risk Factors for HABP/VABP Study
Official title: Prospective Observational Study of the Risk Factors for Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia, Ventilator-Associated
Pneumonia, Bacterial
Pneumonia, Hospital-Acquired
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Clinical Trials Transformation Initiative
name: Food and Drug Administration (FDA)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2016-02-24
Enrollment: 7530
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All ICU patients at participating sites hospitalized for \>48 hours or admitted \<7 days after discharge from an inpatient acute or chronic care facility

Brief summary: 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: 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antibiotics for either indication will subsequently be screened for the development of pneumonia, as defined by the FDA draft guidance document for drug development in HABP/VABP. Subjects who meet the FDA draft guidance definition of pneumonia will have vitals and physiologic data collected and will be followed for 4 days after pneumonia is diagnosed to capture the results of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.

Eligibility criteria: 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)

Primary outcomes:
measure: Development of HABP/VABP
timeFrame: Through completion of the study, up to 12 months
measure: Eligibility for typical antibacterial clinical trial
timeFrame: Through completion of the study, up to 12 months
Secondary outcomes:
measure: In enrolled subjects, what factors are associated with the development of hospital acquired or ventilator associated pneumonia.
timeFrame: Through completion of the study, up to 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Royal Oak
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Rochester
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
Study officials:
affiliation: Duke University
name: Vance G Fowler, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bergin SP, Coles A, Calvert SB, Farley J, Powers JH, Zervos MJ, Sims M, Kollef MH, Durkin MJ, Kabchi BA, Donnelly HK, Bardossy AC, Greenshields C, Rubin D, Sun JL, Chiswell K, Santiago J, Gu P, Tenaerts P, Fowler VG Jr, Holland TL. PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU. Chest. 2020 Dec;158(6):2370-2380. doi: 10.1016/j.chest.2020.06.034. Epub 2020 Jun 29.
citation: Bergin SP, Calvert SB, Farley J, Sun JL, Chiswell K, Dieperink W, Kluytmans J, Lopez-Delgado JC, Leon-Lopez R, Zervos MJ, Kollef MH, Sims M, Kabchi BA, Rubin D, Santiago J, Natarajan M, Tenaerts P, Fowler VG, Holland TL, Bonten MJ, Hullegie SJ. PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts. Open Forum Infect Dis. 2022 May 9;9(7):ofac231. doi: 10.1093/ofid/ofac231. eCollection 2022 Jul.
citation: Ericson JE, McGuire J, Michaels MG, Schwarz A, Frenck R, Deville JG, Agarwal S, Bressler AM, Gao J, Spears T, Benjamin DK Jr, Smith PB, Bradley JS; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee and the Clinical Trials Transformation Initiative. Hospital-acquired Pneumonia and Ventilator-associated Pneumonia in Children: A Prospective Natural History and Case-Control Study. Pediatr Infect Dis J. 2020 Aug;39(8):658-664. doi: 10.1097/INF.0000000000002642.