The APS Phenotyping Study

NCT ID: NCT06521502

Last Updated: 2025-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

4000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-07-25

Study Completion Date

2028-04-30

Brief Summary

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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

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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.

Conditions

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ARDS Sepsis Pneumonia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort A (full study protocol - written informed consent)

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.

Blood collection

Intervention Type OTHER

Blood will be collected from a catheter ("IV") that is already in place or using a needle stick into a vein.

Blood will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort).

Urine Collection

Intervention Type OTHER

Urine will be collected through a urinary catheter that is already in place or by urinating into a cup.

Urine will be collected in hospital only (Cohorts A, B)

Nasal, oral, and rectal swabs

Intervention Type OTHER

Nasal, oral, and rectal swabs inserted into the nose, mouth, and rectum, respectively. The swabs will be rubbed inside the cavity and then removed the swab.

Oral and nasal swabs will also be collected in hospital (Cohort A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

Stool collection

Intervention Type OTHER

Stool will be collected either in a cup after defecation or by collecting it from a tube or bag that may already be in place that is catching stool.

Stool will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization (Long Term Outcomes Cohort).

Heat Moisture Exchange Filter collection

Intervention Type OTHER

An HME filter is a sponge that is placed in the tubing between a patient and breathing machine. It reduces the amount of heat and moisture a patient loses when on a breathing machine. Moisture from breath is collected in this filter. The filter is changed every few hours. When the filter is changed, it will be saved to collect the moisture that it contains and run tests on it.

HME filters will be collected in hospital on intubated patients only (Cohorts A, B).

Tracheal Aspirate sample collection

Intervention Type OTHER

Patients on a breathing machine have a breathing tube in their trachea that connects their lungs to the breathing machine. A smaller tube, called a suction catheter, will be placed through the larger tube and fluid will be gently sucked out.

Tracheal aspirate will be collected in hospital on intubated patients only (Cohorts A, B)

Non-bronchoscopic bronchoalveolar lavage (NBBAL)

Intervention Type PROCEDURE

The NBBAL procedure involves putting a flexible rubber tube through the breathing tube into the airway of one of the lungs. A small amount of fluid is injected into the lung and then a gentle suction is used to collect fluid. Only patients who pass a safety screen showing that they are not at high risk for complications will have the NBBAL procedure performed.

NBBAL will be performed in hospital on intubated patients only (Cohort A)

Surveys

Intervention Type OTHER

Participants will be contacted by email, text, and /or phone to give updates about their health. These surveys will ask questions about quality of life, mental health, return to work, and re-admission to the hospital. (Cohort A)

Cohort B (alteration study protocol - alteration of informed consent)

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.

Blood collection

Intervention Type OTHER

Blood will be collected from a catheter ("IV") that is already in place or using a needle stick into a vein.

Blood will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort).

Urine Collection

Intervention Type OTHER

Urine will be collected through a urinary catheter that is already in place or by urinating into a cup.

Urine will be collected in hospital only (Cohorts A, B)

Nasal, oral, and rectal swabs

Intervention Type OTHER

Nasal, oral, and rectal swabs inserted into the nose, mouth, and rectum, respectively. The swabs will be rubbed inside the cavity and then removed the swab.

Oral and nasal swabs will also be collected in hospital (Cohort A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

Stool collection

Intervention Type OTHER

Stool will be collected either in a cup after defecation or by collecting it from a tube or bag that may already be in place that is catching stool.

Stool will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization (Long Term Outcomes Cohort).

Heat Moisture Exchange Filter collection

Intervention Type OTHER

An HME filter is a sponge that is placed in the tubing between a patient and breathing machine. It reduces the amount of heat and moisture a patient loses when on a breathing machine. Moisture from breath is collected in this filter. The filter is changed every few hours. When the filter is changed, it will be saved to collect the moisture that it contains and run tests on it.

HME filters will be collected in hospital on intubated patients only (Cohorts A, B).

Tracheal Aspirate sample collection

Intervention Type OTHER

Patients on a breathing machine have a breathing tube in their trachea that connects their lungs to the breathing machine. A smaller tube, called a suction catheter, will be placed through the larger tube and fluid will be gently sucked out.

Tracheal aspirate will be collected in hospital on intubated patients only (Cohorts A, B)

Long-term Outcomes Cohort

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.

Blood collection

Intervention Type OTHER

Blood will be collected from a catheter ("IV") that is already in place or using a needle stick into a vein.

Blood will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort).

Nasal, oral, and rectal swabs

Intervention Type OTHER

Nasal, oral, and rectal swabs inserted into the nose, mouth, and rectum, respectively. The swabs will be rubbed inside the cavity and then removed the swab.

Oral and nasal swabs will also be collected in hospital (Cohort A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

Stool collection

Intervention Type OTHER

Stool will be collected either in a cup after defecation or by collecting it from a tube or bag that may already be in place that is catching stool.

Stool will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization (Long Term Outcomes Cohort).

Short physical performance battery

Intervention Type OTHER

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort)

Chair Stand Test: For this test the participant will sit in a chair. They will then stand as quickly as possible without using their upper body to assist them.

Balance Test: For this test the participant will stand unsupported for 10 seconds with their feet in 3 different positions.

4-meter walk: For this test the participant will walk 4 meters as quickly as possible.

Hand grip strength

Intervention Type OTHER

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will squeeze a machine called a hand-held dynamometer 3 times with all their strength.

CNS Vital Signs

Intervention Type OTHER

At visits 3, 6, and 12 months following hospitalization (Cohort A - Long-term Outcomes Cohort):

The participant will sit at a computer and follow the prompts on the screen. This test takes about 45 minutes.

Muscle Ultrasound

Intervention Type OTHER

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will undergo ultrasound on the quadriceps muscle on the dominant side of their body.

Muscle Strength

Intervention Type OTHER

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort):

A dynamometer will be used to measure muscle strength in the dominant leg.

Spirometry

Intervention Type OTHER

At a visit 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will have a clip placed on their nose and will be given a plastic mouthpiece that is connected to a machine called a spirometer. They will place their lips tightly around the mouthpiece and take in as big and deep of a breath as possible and then blow out as hard and fast as they can.

Lung Diffusion Testing (DLCO)

Intervention Type OTHER

At a visit 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will have a clip on their nose. They will put their mouth over a mouthpiece that is attached to a machine. This machine will deliver a small amount of carbon dioxide when they breathe in and will also record the results of the test. They will then take a few normal breaths. Next they will inhale deeply and exhale completely. They will breathe in quickly through their mouth and hold their breath for 10 seconds or as long as they can. Then they will breathe out.

Chest CT Scan

Intervention Type RADIATION

At a visit 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will undergo a Chest Computed Tomography (CT) scan which uses special X-ray equipment to take detailed pictures of the lungs.

Interventions

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Blood collection

Blood will be collected from a catheter ("IV") that is already in place or using a needle stick into a vein.

Blood will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort).

Intervention Type OTHER

Urine Collection

Urine will be collected through a urinary catheter that is already in place or by urinating into a cup.

Urine will be collected in hospital only (Cohorts A, B)

Intervention Type OTHER

Nasal, oral, and rectal swabs

Nasal, oral, and rectal swabs inserted into the nose, mouth, and rectum, respectively. The swabs will be rubbed inside the cavity and then removed the swab.

Oral and nasal swabs will also be collected in hospital (Cohort A, B) and at visits 3, 6, and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

Intervention Type OTHER

Stool collection

Stool will be collected either in a cup after defecation or by collecting it from a tube or bag that may already be in place that is catching stool.

Stool will be collected in hospital (Cohorts A, B) and at visits 3, 6, and 12 months following hospitalization (Long Term Outcomes Cohort).

Intervention Type OTHER

Heat Moisture Exchange Filter collection

An HME filter is a sponge that is placed in the tubing between a patient and breathing machine. It reduces the amount of heat and moisture a patient loses when on a breathing machine. Moisture from breath is collected in this filter. The filter is changed every few hours. When the filter is changed, it will be saved to collect the moisture that it contains and run tests on it.

HME filters will be collected in hospital on intubated patients only (Cohorts A, B).

Intervention Type OTHER

Tracheal Aspirate sample collection

Patients on a breathing machine have a breathing tube in their trachea that connects their lungs to the breathing machine. A smaller tube, called a suction catheter, will be placed through the larger tube and fluid will be gently sucked out.

Tracheal aspirate will be collected in hospital on intubated patients only (Cohorts A, B)

Intervention Type OTHER

Non-bronchoscopic bronchoalveolar lavage (NBBAL)

The NBBAL procedure involves putting a flexible rubber tube through the breathing tube into the airway of one of the lungs. A small amount of fluid is injected into the lung and then a gentle suction is used to collect fluid. Only patients who pass a safety screen showing that they are not at high risk for complications will have the NBBAL procedure performed.

NBBAL will be performed in hospital on intubated patients only (Cohort A)

Intervention Type PROCEDURE

Surveys

Participants will be contacted by email, text, and /or phone to give updates about their health. These surveys will ask questions about quality of life, mental health, return to work, and re-admission to the hospital. (Cohort A)

Intervention Type OTHER

Short physical performance battery

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort)

Chair Stand Test: For this test the participant will sit in a chair. They will then stand as quickly as possible without using their upper body to assist them.

Balance Test: For this test the participant will stand unsupported for 10 seconds with their feet in 3 different positions.

4-meter walk: For this test the participant will walk 4 meters as quickly as possible.

Intervention Type OTHER

Hand grip strength

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will squeeze a machine called a hand-held dynamometer 3 times with all their strength.

Intervention Type OTHER

CNS Vital Signs

At visits 3, 6, and 12 months following hospitalization (Cohort A - Long-term Outcomes Cohort):

The participant will sit at a computer and follow the prompts on the screen. This test takes about 45 minutes.

Intervention Type OTHER

Muscle Ultrasound

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will undergo ultrasound on the quadriceps muscle on the dominant side of their body.

Intervention Type OTHER

Muscle Strength

At visits 3, 6, and 12 months following hospitalization (Long-term Outcomes Cohort):

A dynamometer will be used to measure muscle strength in the dominant leg.

Intervention Type OTHER

Spirometry

At a visit 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will have a clip placed on their nose and will be given a plastic mouthpiece that is connected to a machine called a spirometer. They will place their lips tightly around the mouthpiece and take in as big and deep of a breath as possible and then blow out as hard and fast as they can.

Intervention Type OTHER

Lung Diffusion Testing (DLCO)

At a visit 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will have a clip on their nose. They will put their mouth over a mouthpiece that is attached to a machine. This machine will deliver a small amount of carbon dioxide when they breathe in and will also record the results of the test. They will then take a few normal breaths. Next they will inhale deeply and exhale completely. They will breathe in quickly through their mouth and hold their breath for 10 seconds or as long as they can. Then they will breathe out.

Intervention Type OTHER

Chest CT Scan

At a visit 12 months following hospitalization (Long-term Outcomes Cohort):

The participant will undergo a Chest Computed Tomography (CT) scan which uses special X-ray equipment to take detailed pictures of the lungs.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Wesley Self

APS Consortium Coordinating Center Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wesley H. Self, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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Fresno Community Hospital and Medical Center

Fresno, California, United States

Site Status NOT_YET_RECRUITING

Stanford University

Palo Alto, California, United States

Site Status NOT_YET_RECRUITING

San Francisco General Hospital

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

University of Colorado, Denver

Denver, Colorado, United States

Site Status RECRUITING

Denver Health and Hospital Authority

Denver, Colorado, United States

Site Status NOT_YET_RECRUITING

National Jewish Health

Denver, Colorado, United States

Site Status NOT_YET_RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

Johns Hopkins Univeristy

Baltimore, Maryland, United States

Site Status NOT_YET_RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status NOT_YET_RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

Duke University

Durham, North Carolina, United States

Site Status NOT_YET_RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status NOT_YET_RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

Meharry Medical College

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Intermountain Medical Center

Murray, Utah, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Wesley H. Self, MD, MPH

Role: CONTACT

1-615-936-8047

Jillian P. Rhoads, PhD

Role: CONTACT

1-615-936-3773

Facility Contacts

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Eyad Almasri, MD

Role: primary

Angela Rogers, MD

Role: primary

Carolyn Hendrickson, MD, MPH

Role: primary

Carolyn Calfee, MD

Role: primary

Marc Moss, MD

Role: primary

Ivor Douglas, MD, FRCP

Role: primary

William Janssen, MD

Role: primary

Krysta Wolfe, MD

Role: primary

Dale Needham, MD, PhD

Role: primary

Robert Hyzy, MD

Role: primary

Pratik Sinha, MBChB, PhD

Role: primary

Christina Barkauskas, MD

Role: primary

R. Duncan Hite, MD

Role: primary

Nuala Meyer, MD, MS

Role: primary

Richard Freemont, MD

Role: primary

Wesley H. Self, MD

Role: primary

615.936.8047

Samuel Brown, MD, MS

Role: primary

Estelle Harris, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 32150460 (View on PubMed)

Related Links

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http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-23-001.html

Notice of Funding Opportunity (NOFO) for APS Consortium

Other Identifiers

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240088

Identifier Type: -

Identifier Source: org_study_id

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