The APS Phenotyping Study

February 18, 2026 updated by: Wesley Self, Vanderbilt University Medical Center

The ARDS, Pneumonia, and Sepsis (APS) Consortium: A Prospective Observational Study to Evaluate Phenotypes

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

4000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Fresno, California, United States, 93721
        • Recruiting
        • Fresno Community Hospital and Medical Center
        • Contact:
      • Palo Alto, California, United States, 94305
      • San Francisco, California, United States, 94143
      • San Francisco, California, United States, 94110
    • Colorado
      • Denver, Colorado, United States, 80045
      • Denver, Colorado, United States, 80206
      • Denver, Colorado, United States, 80204
      • Loveland, Colorado, United States, 80538
    • Illinois
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Recruiting
        • Johns Hopkins Univeristy
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
    • North Carolina
    • Ohio
      • Cincinnati, Ohio, United States, 45219
    • Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Principal Investigator:
          • Lorraine Ware, MD
        • Contact:
      • Nashville, Tennessee, United States, 37208
        • Recruiting
        • Meharry Medical College
        • Contact:
    • Utah
      • Murray, Utah, United States, 84107
      • Salt Lake City, Utah, United States, 84132

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
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)

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).

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)

Procedure: 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)

Other: 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)
Other: 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 and 12 months following hospitalization for (Long-term Outcomes Cohort).

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 and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

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 and 12 months following hospitalization (Long Term Outcomes Cohort).
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.
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)

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).

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)

Other: 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 and 12 months following hospitalization for (Long-term Outcomes Cohort).

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 and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

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 and 12 months following hospitalization (Long Term Outcomes Cohort).
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- 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.
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.

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.

Radiation: 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.

Other: 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 and 12 months following hospitalization for (Long-term Outcomes Cohort).

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 and 12 months following hospitalization for (Long-term Outcomes Cohort). Rectal swabs will be collected in hospital only (Cohorts A, B).

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 and 12 months following hospitalization (Long Term Outcomes Cohort).

Other: Short physical performance battery

At visits 3 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.

Other: Hand grip strength

At visits 3 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.

Other: CNS Vital Signs

At visits 3 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.

Other: Muscle Ultrasound

At visits 3 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.

Other: Muscle Strength

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ARDS, pneumonia, and sepsis classification
Time Frame: 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.
Through day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death
Time Frame: 28 days, 3 months, 12 months
All-cause mortality
28 days, 3 months, 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Invasive ventilator free days
Time Frame: In-hospital through day 28
Days alive and free of invasive mechanical ventilation through day 28
In-hospital through day 28
Ventilatory support free days
Time Frame: In-hospital through day 28
Days alive and free of invasive mechanical ventilation (IMV), non-invasive ventilation (NIV), and high flow nasal cannula (HFNC) through day 28
In-hospital through day 28
Vasopressor free days
Time Frame: In-hospital through day 28
Days alive and free of vasopressor use through day 28
In-hospital through day 28
New kidney replacement therapy free days
Time Frame: In-hospital through day 28
Days alive and free of new kidney replacement free days through day 28
In-hospital through day 28
Organ support free days
Time Frame: In-hospital through day 28
Days alive and free of IMV, NIV, HFNC, vasopressors, and new kidney replacement therapy
In-hospital through day 28
Coma and delirium free days
Time Frame: In hospital through day 7
Days alive and free of coma and delirium (defined by confusion assessment method (CAM)-ICU and Richmond Agitation Sedation Scale (RASS score) through day 7
In hospital through day 7
Oxygen free days
Time Frame: In hospital through day 28
Days alive and free of new supplemental oxygen therapy through day 28
In hospital through day 28
Hospital free days
Time Frame: In hospital through day 28
Days alive and out of the hospital through day 28
In hospital through day 28
ICU free days
Time Frame: In hospital through day 28
Days alive and out of the ICU through day 28
In hospital through day 28
Acute kidney injury (AKI)
Time Frame: In hospital through day 28
AKI defined by creatinine criteria from Kidney Disease Improving Global Outcomes (KDIGO)
In hospital through day 28
Major adverse kidney events (MAKE)
Time Frame: In-hospital through day 28
Death, new kidney replacement therapy, or persistent doubling of serum creatinine
In-hospital through day 28
Extracorporeal membrane oxygenation (ECMO)
Time Frame: In-hospital through day 28
New receipt of ECMO therapy
In-hospital through day 28
Sequential Organ Failure Assessment (SOFA) score
Time Frame: Through day 7
Organ dysfunction scoring system that assesses the performance of 6 organ systems (respiratory, cardiovascular, hepatic, renal, coagulation, and neurological). Score range is 0 to 24. A higher score indicates greater (worse) organ dysfunction.
Through day 7
Pulmonary spirometry, including forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1).
Time Frame: 12 months
FVC is the volume of air that can be forcibly exhaled after full inspiration, measured in liters. FEV1 is the volume of air that can be forcibly exhaled in 1 second after full inspiration, measured in liters.
12 months
Diffusing capacity for carbon monoxide (DLCO)
Time Frame: 12 months
Lung function assessment
12 months
EuroQol-5 Dimension-5 Level (EQ-5D-5L) quality of life assessment
Time Frame: 3, 6, 12 months
A tool to measure health related quality of life. A score of 1 indicates the best possible health state and a score <0 is the worst possible health state.
3, 6, 12 months
Impact of Event Scale (IES)-6
Time Frame: 3, 6, 12 months
PTSD assessment scored out of 4, with a score of ≥ 1.75 denoting likely PTSD
3, 6, 12 months
Hospital Anxiety and Depression Scale (HADS)
Time Frame: 3, 6, 12 months
A fourteen-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression.
3, 6, 12 months
Modified Medical Research Council (mMRC) dyspnea score
Time Frame: 3, 6, 12 months
The mMRC scale is a self-assessment tool used to measure the level of impairment caused by breathlessness during daily activities, rated on a scale from 0 (no breathlessness) to 4 (severe limitation).
3, 6, 12 months
Clinical frailty scale
Time Frame: 3, 6, 12 months
A nine-point scale based on clinical evaluation of mobility, energy, physical activity, and function. Higher scores indicate increased frailty.
3, 6, 12 months
World Health Organization Disability Assessment Schedule (WHODAS) 2.0
Time Frame: 3, 6, 12 months
A tool that measures how a health condition affects a person's ability to function in everyday life. Scored from 0-100 where 0 indicates no disability and 100 indicates full disability.
3, 6, 12 months
Return to work
Time Frame: 3, 6, 12 months
Assessment of returning to work after critical illness
3, 6, 12 months
Financial toxicity
Time Frame: 3, 6, 12 months
Assessment of financial stress after critical illness
3, 6, 12 months
Housing instability
Time Frame: 3, 6, 12 months
Assessment of housing after critical illness
3, 6, 12 months
Central Nervous System (CNS) vital signs score
Time Frame: 3, 12 months
CNS vital signs is a computer-based neurocognitive assessment that evaluates memory, psychomotor speed, reaction time, complex attention and cognitive flexibility. The summary score is called the Neurocognitive Index. Scoring produces a relative score for the individual relative to the American normative sample controlled for age; mean score is 100; the standard deviation is 15; higher scores represent better neurocognitive function.
3, 12 months
Short Physical Performance Battery Protocol
Time Frame: 3, 12 months
Physical performance assessment
3, 12 months
Handgrip strength
Time Frame: 3, 12 months
Physical strength assessment
3, 12 months
Quadriceps muscle ultrasound
Time Frame: 3, 12 months
Physical muscle fitness assessment
3, 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Investigators

  • Principal Investigator: Wesley H. Self, MD, MPH, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2024

Primary Completion (Estimated)

April 30, 2029

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

July 16, 2024

First Submitted That Met QC Criteria

July 20, 2024

First Posted (Actual)

July 26, 2024

Study Record Updates

Last Update Posted (Actual)

February 20, 2026

Last Update Submitted That Met QC Criteria

February 18, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 240088

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

During conduct of the APS Consortium study procedures, data, biospecimens, and radiographic images will be collected by enrolling sites and transmitted to the APS Consortium Coordinating Center at Vanderbilt University Medical Center. Data and biospecimens will be organized and catalogued at the coordinating center. Additionally, the coordinating center will periodically transmit data and biospecimens to repositories managed by the National Heart, Lung, and Blood Institute (NHLBI) -- BioData Catalyst (data repository) and BioLINCC (biospecimen repository).

During the period of performance for the APS Consortium, requests for data and/or biospecimens for use in ancillary studies will be reviewed for approval by the APS Steering Committee.

After the completion of the APS Consortium period of performance, requests for data and/or biospecimens for use in ancillary studies will be governed by NHLBI through the BioData Catalyst and BioLINCC programs.

IPD Sharing Time Frame

The first large subset of APS data and biospecimens is anticipated to be available for distribution no earlier than the first quarter of calendar year 2026. The full cohort of data and biospecimens will be available in 2028.

IPD Sharing Access Criteria

Requests for use of biospecimens and/or data will be reviewed by the APS Consortium Steering Committee through the end of the program. After the program has completed, requests will be reviewed by the US National Heart, Lung, and Blood Institute (NHLBI).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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