Clinical trial NCT05074875: COVID-19 Respiratory Outcomes Registry
Official title: Post COVID-19 Hypoxemic Respiratory Failure Residual Pathophysiologic Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2021-10-12
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects with a diagnosis of COVID-19 who require therapy with supplemental oxygen and who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Brief summary: This is a 48-week, observational study looking to see if the inflammatory process of hypoxemic respiratory failure associated with COVID-19 leads to progressive pulmonary fibrosis. Inpatient, as well as outpatient adults with recent COVID-19 hospitalization will be recruited. Data from hospitalization will be collected and subjects will return to the center for follow-up visits. Subjects will undergo the following procedures: High Resolution Computed Tomography (HRCT) of the chest, Pulmonary Function Tests (PFT), Muscle Strength Measurement, and blood draw for biomolecular data such as biomarkers found in ribonucleic acid (RNA), deoxyribonucleic acid (DNA), serum, and plasma. Quality of Life (QoL) measurements will also be collected through the study.

Detailed description: This is a multi-center, observational, and prospective study collecting data on subjects who were hospitalized with hypoxemic respiratory failure associated with COVID-19 or patients who have evidence of an outpatient COVID-19 infection that have been treated with supplemental oxygen.

A total of approximately 300 subjects will be enrolled in the study. Subjects will be enrolled into one of 3 cohorts.

Cohort 1: Inpatient Enrollment: Subjects enrolled while hospitalized for COVID-19, prior to discharge.

Cohort 2: Outpatient Enrollment: Subjects enrolled up to 4 weeks after discharge from hospitalization for COVID-19 or 4 weeks post their outpatient COVID -19 infection.

Cohort 3: Outpatient Enrollment: Subjects enrolled between 6 and 24 weeks after discharge from hospitalization for COVID-19 or 6 and 24 weeks post their outpatient COVID -19 infection. Cohort 3 will be sub-divided into 3a and 3b depending on the timepoint of enrollment.

After signing the Informed Consent Form, the screening visit will be performed. Screening and enrollment can occur at Visit 0 (inpatient) or Visit 1 (outpatient). Following completion of Visit 0 or 1 the subjects' data will be assessed by the investigator to confirm eligibility and a decision will be made if the patient is to be enrolled. If not the reason for non-enrollment will be listed in the trial log.

Each subject will either have a total of 4 or 5 visits, depending on if subjects complete enrollment while still admitted to the hospital (Visit 0) or at Visit 1. At weeks 4, 24, 36, 48, all subjects will complete questionnaires, have physical exams, spirometry test with DLCO, HRCTs, 6MWTs, blood draws, and review of medical history since the previous visit.

The primary analysis of this study will be performed once the last enrolled subject reaches Week 48. At that time, there will be a data-base lock. Unless otherwise noted, Visit 1 is treated as baseline measurement. In addition, for patients enrolled at discharge, a second set of analysis will be performed treating Visit 0 as baseline for the measurements collected at Visit 0.

Aim 1: To identify whether the trajectory of COVID-19 associated respiratory failure results in progressive pulmonary fibrosis with clinical features or biomolecular changes.

Aim 2: To identify biomarkers that may indicate those patients at risk for developing a chronic fibrotic HRCT pattern that may go on to progression.

Eligibility criteria: Inclusion Criteria:

1. Written Informed Consent consistent with International Conference on Harmonization Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study
2. Male or female ≥ 18 years of age at the time of consent
3. SARS-CoV-2 positive confirmed by a positive serology or PCR or antigen test
4. COVID-19 induced hypoxemia or reduced oxygen saturation requiring treatment with supplemental oxygen.
5. COVID-19 hospital discharge date or outpatient COVID-19 infection within 24 weeks of enrollment

Exclusion Criteria:

1. Diagnosed with Fibrotic Interstitial Lung Disease (ILD) prior to COVID-19 infection.
2. Prior treatment with an antifibrotic agent, including nintedanib or pirfenidone
3. Pregnant women or women planning on becoming pregnant in the next 12 months
4. Patients planned for discharge from the hospital to hospice
5. Patients with significant cognitive impairment

Primary outcomes:
measure: Change in fibrotic and non-fibrotic interstitial opacities on chest HRCT at 48 weeks after hospitalization for COVID-19 or outpatient COVID-19 infections which require treatment with supplemental oxygen
timeFrame: 48 Weeks
Secondary outcomes:
measure: Changes from baseline and evidence of disease progression seen on high resolution computed tomography
timeFrame: 72 Weeks
measure: Changes from baseline and evidence of disease progression on pulmonary function testing
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression seen on pulmonary function testing
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression see on pulmonary function testing
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression via 6 Minute Walk Test
timeFrame: 72 weeks
measure: Change in pre- and post- six minute walk test Borg Scale Dyspnea score from baseline and at 12, 24, and 48 weeks.
timeFrame: 72 weeks
measure: Change in pre- and post- six minute walk test Borg Scale Fatigue score from baseline and at 12, 24, and 48 weeks.
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression by Hand Grip Strength
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. EuroQol-5D (EQ-5D)
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. St. George's Respiratory Questionnaire (SGRQ)
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. Generalized Anxiety 7-Item (GAD-7)
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. Patient Health Questionnaire 9 (PHQ-9)
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes- Impact of Events Scale Revised (IES-R)
timeFrame: 72 weeks
measure: Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes- PROMIS-29 + 2 Profile
timeFrame: 72 weeks
measure: Examine the effects of COVID-19 on the presence of molecular biomarkers associated with Interstitial Lung Disease
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University of St. Louis
state: Missouri
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: WCM Associate Professor of Clinical Medicine Associate Attending
name: Robert J Kaner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boehringer Ingelheim
name: Craig S Conoscenti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boehringer Ingelheim
name: Nina Patel, MD
role: PRINCIPAL_INVESTIGATOR
References: