The APS Phenotyping Study

Recruiting

• Conditions: ARDS; Sepsis; Pneumonia
• Interventions: Other: Blood collection; Other: Urine Collection; Other: Nasal, oral, and rectal swabs; Other: Stool collection; Other: Short physical performance battery; Other: Heat Moisture Exchange Filter collection; Other: Hand grip strength; Other: Tracheal Aspirate sample collection; Other: CNS Vital Signs; Procedure: Non-bronchoscopic bronchoalveolar lavage (NBBAL); Other: Muscle Ultrasound; Other: Muscle Strength; Other: Surveys; Other: Spirometry; Other: Lung Diffusion Testing (DLCO); Radiation: Chest CT Scan

• Registration Number: NCT06521502
• Lead Sponsor: Vanderbilt University Medical Center

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.

Study Timeline

• Study First Submitted: 2024-07-16
• Study First Submitted QC: 2024-07-20
• Study Start: 2024-07-25
• Study First Posted: 2024-07-26
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-26
• Last Update Posted: 2024-08-27
• Primary Completion: 2028-04-30
• Study Completion: 2028-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4000

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort A (full study protocol - written informed consent)	Blood collection	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort A (full study protocol - written informed consent)	Urine Collection	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort A (full study protocol - written informed consent)	Nasal, oral, and rectal swabs	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort A (full study protocol - written informed consent)	Stool collection	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort A (full study protocol - written informed consent)	Heat Moisture Exchange Filter collection	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort A (full study protocol - written informed consent)	Non-bronchoscopic bronchoalveolar lavage (NBBAL)	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort A (full study protocol - written informed consent)	Tracheal Aspirate sample collection	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort B (alteration study protocol - alteration of informed consent)	Urine Collection	Cohort B is the cohort of APS study participants who are enrolled in the study under alteration of informed consent. Cohort B will participate in a modified set of procedures which omits procedures considered greater than minimal risk.
Long-term Outcomes Cohort	Hand grip strength	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	Muscle Strength	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Cohort A (full study protocol - written informed consent)	Surveys	Cohort A is the cohort of APS study participants who have provided written informed consent for participation in the APS phenotyping study. Cohort A may participate in all study procedures in the APS phenotyping study.
Cohort B (alteration study protocol - alteration of informed consent)	Heat Moisture Exchange Filter collection	Cohort B is the cohort of APS study participants who are enrolled in the study under alteration of informed consent. Cohort B will participate in a modified set of procedures which omits procedures considered greater than minimal risk.
Cohort B (alteration study protocol - alteration of informed consent)	Tracheal Aspirate sample collection	Cohort B is the cohort of APS study participants who are enrolled in the study under alteration of informed consent. Cohort B will participate in a modified set of procedures which omits procedures considered greater than minimal risk.
Long-term Outcomes Cohort	Blood collection	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	Muscle Ultrasound	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	Lung Diffusion Testing (DLCO)	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	Chest CT Scan	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Cohort B (alteration study protocol - alteration of informed consent)	Blood collection	Cohort B is the cohort of APS study participants who are enrolled in the study under alteration of informed consent. Cohort B will participate in a modified set of procedures which omits procedures considered greater than minimal risk.
Cohort B (alteration study protocol - alteration of informed consent)	Stool collection	Cohort B is the cohort of APS study participants who are enrolled in the study under alteration of informed consent. Cohort B will participate in a modified set of procedures which omits procedures considered greater than minimal risk.
Long-term Outcomes Cohort	Short physical performance battery	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Cohort B (alteration study protocol - alteration of informed consent)	Nasal, oral, and rectal swabs	Cohort B is the cohort of APS study participants who are enrolled in the study under alteration of informed consent. Cohort B will participate in a modified set of procedures which omits procedures considered greater than minimal risk.
Long-term Outcomes Cohort	Nasal, oral, and rectal swabs	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	Stool collection	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	CNS Vital Signs	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.
Long-term Outcomes Cohort	Spirometry	The Long-term Outcomes Cohort consists of a subset of participants with written informed consent for study participation (Cohort A) who complete in-person post-hospital study assessments. These in-person study visits are scheduled at 3-, 6-, and 12-months after initial enrollment in the hospital. Interventions/exposures are denoted for this group for study procedures that are completed during an in-person post-hospital visit.

Primary Outcome Measures

Name	Time	Method
ARDS, pneumonia, and sepsis classification	Through day 7	Classification of critically ill adults into disease categories based on published paradigms, including the Berlin Criteria for ARDS, Sepsis-3 criteria for sepsis, and Centers for Disease Control and Prevention (CDC) criteria for pneumonia.

Secondary Outcome Measures

Name	Time	Method
Death	28 days, 3 months, 6 months, 12 months	All-cause mortality

Trial Locations

Locations (19)

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins Univeristy; 🇺🇸 Baltimore, Maryland, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Fresno Community Hospital and Medical Center; 🇺🇸 Fresno, California, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States

San Francisco General Hospital; 🇺🇸 San Francisco, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Meharry Medical College; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of Colorado, Denver; 🇺🇸 Denver, Colorado, United States

Denver Health and Hospital Authority; 🇺🇸 Denver, Colorado, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States