Clinical trial NCT06521502: The APS Phenotyping Study
Official title: The ARDS, Pneumonia, and Sepsis (APS) Consortium: A Prospective Observational Study to Evaluate Phenotypes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: ARDS
Sepsis
Pneumonia
Keywords: acute respiratory distress syndrome
sepsis
pneumonia
phenotype
endotype
critical illness
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2024-07-26
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study enrolls hospitalized adult patients ≥18 years who have or are at high risk of developing ARDS, pneumonia, and/or sepsis.

Brief summary: The goal of the observational APS phenotyping study is to better understand risk factors, potential biomarkers, length and severity of illness, and recovery for adults with ARDS, pneumonia, and/ or sepsis. This study will also generate a biobank of specimens collected from these patients that will be available to investigators for future studies of ARDS, sepsis, and/or pneumonia.

Detailed description: The APS phenotyping study will enroll hospitalized adult patients ≥18 years old who have or are at risk of developing ARDS, sepsis, or pneumonia. Participation in this study will involve collection of clinical data, completing questionnaires, and collection of samples such as blood, urine, and stool. Participants who are mechanically ventilated will also provide samples from their respiratory track. Data and samples will be collected both during and after hospitalization. Analyses to understand the mechanisms underlying ARDS, pneumonia, and sepsis will be conducted, with goals including the classification of patients with ARDS, pneumonia, and sepsis into biologically based phenotype categories and identifying new targets for future therapeutic trials.

Eligibility criteria: Inclusion Criteria:

To be eligible for enrollment, a patient must meet all the following inclusion criteria at the time of the first study-specified biospecimen collection (Time 0):

1. Age ≥ 18 years old
2. Admitted (or planned to be admitted) to an intensive care unit (ICU) or other in-patient hospital location where IV vasopressors or advanced respiratory support (invasive mechanical ventilation, non-invasive ventilation, or high flow nasal cannula) are routinely provided (referred to as an "eligible unit.")
3. Acute cardiovascular or pulmonary organ dysfunction defined by meeting at least one of the two criteria below:

   * New receipt of invasive mechanical ventilation, non-invasive ventilation, high flow nasal cannula, or supplemental oxygen at a flow rate of ≥ 6 lpm for acute hypoxemia.

     a. Patients who use chronic oxygen therapy are eligible to participate if they are receiving at least 6 lpm higher than their baseline oxygen requirement (e.g., a patient on 3 lpm O2 at baseline is eligible if they require ≥9 lpm for hypoxemia) or are started on advanced respiratory support (invasive mechanical ventilation, non- invasive ventilation, or high flow nasal cannula).
   * Receipt of intravenous infusion of a vasopressor medication for at least one hour.
4. Acute cardiovascular or pulmonary organ dysfunction (inclusion criterion #3) is attributed to an acute inflammatory condition, including but not limited to any of the following:

   * Any infection including pneumonia.
   * Aspiration pneumonitis.
   * Pancreatitis.
   * Auto-inflammatory condition such as:

     1. Hemophagocytic lymphohistiocytosis.
     2. Suspected acute rheumatologic or auto-immune disease with pulmonary or cardiovascular manifestations.
     3. Suspected cryptogenic organizing pneumonia presenting acutely.
     4. Suspected diffuse alveolar hemorrhage.
     5. Suspected acute anaphylaxis.
     6. Suspected acute pulmonary drug toxicity.

Exclusion Criteria:

To be eligible for enrollment, a patient must not meet any of the following exclusion criteria at the time of the first study-specified biospecimen collection (Time 0):

1. Patient/legally authorized representative (LAR) declines participation.
2. Acute cardiovascular or pulmonary organ dysfunction (inclusion criterion #3) has been present for \> 48 hours.
3. Patient has been in an eligible unit (inclusion criterion #2) for more than 120 hours (five days).
4. Patient is no longer expected to meet the acute cardiovascular or pulmonary organ dysfunction inclusion criterion (inclusion criterion #3) 24 hours after enrollment.
5. Patient desires comfort measures only.
6. Patient is a prisoner.
7. Patient had out-of-hospital cardiac arrest leading to this hospitalization.
8. Residence immediately before this hospitalization in a long-term acute care facility.
9. Presence of tracheostomy for respiratory failure.
10. Home invasive mechanical ventilation or non-invasive ventilation (except patients with non-invasive ventilation prescribed as a treatment for a sleep disorder may participate).
11. Suspected cause of the patient's acute cardiovascular and/or pulmonary dysfunction (inclusion criterion #3) is an alternative condition (not ARDS, pneumonia, or sepsis), including but not limited to the list below:

    * Drug overdose (without aspiration, lung injury, pneumonia, or infection).
    * Trauma (without aspiration, pneumonia, or infection).
    * Chronic lung disease without suspected infection, aspiration, or inflammation.
    * Asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, interstitial lung disease, neuromuscular respiratory failure.
    * Status epilepticus.
    * Acute pulmonary embolism.
    * Acute decompensated heart failure.
    * Diabetic ketoacidosis.
    * Acute stroke or intracranial hemorrhage.
    * Acute bleeding (GI bleeding, post-procedural bleeding, hemolysis).
    * Cytokine release syndrome due to chemotherapy.
12. Inability or unwillingness to complete study-specified blood draws, for example, due to local policies about hemoglobin thresholds for research blood draws.

Primary outcomes:
measure: ARDS, pneumonia, and sepsis classification
timeFrame: Through day 7
Secondary outcomes:
measure: Death
timeFrame: 28 days, 3 months, 6 months, 12 months
Other outcomes:
measure: Invasive ventilator free days
timeFrame: In-hospital through day 28
measure: Ventilatory support free days
timeFrame: In-hospital through day 28
measure: Vasopressor free days
timeFrame: In-hospital through day 28
measure: New kidney replacement therapy free days
timeFrame: In-hospital through day 28
measure: Organ support free days
timeFrame: In-hospital through day 28
measure: Coma and delirium free days
timeFrame: In hospital through day 7
measure: Oxygen free days
timeFrame: In hospital through day 28
measure: Hospital free days
timeFrame: In hospital through day 28
measure: ICU free days
timeFrame: In hospital through day 28
measure: Acute kidney injury (AKI)
timeFrame: In hospital through day 28
measure: Major adverse kidney events (MAKE)
timeFrame: In-hospital through day 28
measure: Extracorporeal membrane oxygenation (ECMO)
timeFrame: In-hospital through day 28
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: Through day 7
measure: Central Nervous System (CNS) vital signs score
timeFrame: 3, 6, 12 months
measure: Short Physical Performance Battery Protocol
timeFrame: 3, 6, 12 months
measure: Handgrip strength
timeFrame: 3, 6, 12 months
measure: Quadriceps muscle ultrasound
timeFrame: 3, 6, 12 months
measure: Pulmonary spirometry, including forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1).
timeFrame: 12 months
measure: Diffusing capacity for carbon monoxide (DLCO)
timeFrame: 12 months
measure: EuroQol-5 Dimension-5 Level (EQ-5D-5L) quality of life assessment
timeFrame: 3, 6, 12 months
measure: Impact of Event Scale (IES)-6
timeFrame: 3, 6, 12 months
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 3, 6, 12 months
measure: Modified Medical Research Council (mMRC) dyspnea score
timeFrame: 3, 6, 12 months
measure: Clinical frailty scale
timeFrame: 3, 6, 12 months
measure: World Health Organization Disability Assessment Schedule (WHODAS) 2.0
timeFrame: 3, 6, 12 months
measure: Return to work
timeFrame: 3, 6, 12 months
measure: Financial toxicity
timeFrame: 3, 6, 12 months
measure: Housing instability
timeFrame: 3, 6, 12 months
Locations:
city: Fresno
country: United States
facility: Fresno Community Hospital and Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Univeristy
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Vanderbilt University Medical Center
name: Wesley H. Self, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Semler MW, Bernard GR, Aaron SD, Angus DC, Biros MH, Brower RG, Calfee CS, Colantuoni EA, Ferguson ND, Gong MN, Hopkins RO, Hough CL, Iwashyna TJ, Levy BD, Martin TR, Matthay MA, Mizgerd JP, Moss M, Needham DM, Self WH, Seymour CW, Stapleton RD, Thompson BT, Wunderink RG, Aggarwal NR, Reineck LA. Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care. NHLBI Working Group Report. Am J Respir Crit Care Med. 2020 Aug 15;202(4):511-523. doi: 10.1164/rccm.201908-1595WS.