CTTI Risk Factors for HABP/VABP Study (PROPHETIC)

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

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).

Study Overview

• Status: Completed
• Conditions: Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pneumonia, Hospital-Acquired

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for either indication will subsequently be screened for the development of pneumonia, as defined by the FDA draft guidance document for drug development in HABP/VABP. Subjects who meet the FDA draft guidance definition of pneumonia will have vitals and physiologic data collected and will be followed for 4 days after pneumonia is diagnosed to capture the results of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

• Study Type: Observational
• Enrollment (Actual): 7530

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
  • California
    • Los Angeles, California, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Michigan
    • Detroit, Michigan, United States
    • Royal Oak, Michigan, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New York
    • Rochester, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
High-Risk (Adult =>18 years old); 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; 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); 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); Currently treated with mechanical ventilation via endotracheal intubation for at least 5 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Food and Drug Administration (FDA); Clinical Trials Transformation Initiative
• Investigators: Principal Investigator: Vance G Fowler, MD, MHS, Duke University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: February 11, 2016
• First Submitted That Met QC Criteria: February 18, 2016
• First Posted (Estimated): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: Pro00068313

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Following completion of the study, the results of this research will be written up in a manuscript to be submitted to a scientific journal. The IPD and analysis dataset are available on Vivli.org.
• IPD Sharing Time Frame: The IPD and analysis dataset are available on Vivli.org
• IPD Sharing Access Criteria: Complete data request process at vivli.org.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: VIV00008648