COVID-19 Respiratory Outcomes Registry

NCT ID: NCT05074875

Last Updated: 2023-07-27

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

COMPLETED

Total Enrollment

37 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-01-15

Study Completion Date

2023-05-09

Brief Summary

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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

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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.

Conditions

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Covid19

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1

Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks

Questionnaires and Patient Reported Outcomes (PROs)

Intervention Type OTHER

* EuroQol 5 Dimensional Quality of Life Questionnaire (EQ-5D).
* St. George's Respiratory Questionnaire (SGRQ)
* Impact of Events Scale Revised (IES-R)
* Generalized Anxiety Disorder 7-Item (GAD-7)
* Patient Health Questionnaire (PHQ-9)

Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)

Intervention Type DIAGNOSTIC_TEST

If required by the local site's COVID-19 guidelines, subjects should have the COVID-19 RT-PCR Nasal Swab collected at the beginning of the visit or within 5 days prior to the scheduled visit.

Blood Samples for Biomarkers

Intervention Type GENETIC

Venous blood will be collected using pre-labeled tubes.

High Resolution Computed Tomography

Intervention Type DIAGNOSTIC_TEST

Subjects will have HRCTs at Visits 1, 2, 3, and 4. Inpatient HRCT scans will be collected during the baseline visit (V0 or V1)

Physical Exam and Vital Signs

Intervention Type DIAGNOSTIC_TEST

A complete physical exam, including height, weight, general appearance, neck, lungs, cardiovascular system, abdomen, extremities, and skin will be performed at Visit 1.A brief physical exam will be completed at subsequent visits, including weight, general appearance, lungs, cardiovascular symptoms, extremities, and other body systems pertinent to the participants health status, at the discretion of the investigator.

Blood pressure, heart rate, and oxygen saturation will be collected at all visits, prior to blood draws and after subjects have rested.

Medical Research Council Sum Score

Intervention Type DIAGNOSTIC_TEST

The Medical Research Council Sum Score (MRC-SS) is used globally to detect peripheral muscle strength and to help diagnose ICU-acquired muscle weakness. The MRC-SS ranging from 0 (complete paralysis) to 60 (normal).

Hand Grip Strength

Intervention Type DIAGNOSTIC_TEST

Each subject will have hand grip strength measured at each visit. This is being done in order to assess the maximum isometric strength of hand and forearm muscles.

Spirometry

Intervention Type DIAGNOSTIC_TEST

Spirometry will be assessed at Visits 1, 2, 3 and 4. Each site will use its own spirometry machine. Each subject should use the same machine at each visit and conduct measurements at approximately the same time. Before any testing, the maneuver should be demonstrated to the subject. The spirometry should be reviewed by the investigator.

Diffusing Capacity of Carbon Monoxide

Intervention Type DIAGNOSTIC_TEST

The site will use its own DLCO equipment for measurements at Visits, 1, 2, 3, and 4. The Single-breath DLCO maneuver will be carried out in accordance with the 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Subjects should use the same device at approximately that same time at each visit. The maneuver should be demonstrated to the subject prior to the test.

6 Minute Walk Test

Intervention Type DIAGNOSTIC_TEST

The 6 Minute Walk Test (6MWT) will assess exercise capacity and tolerance. 6MWTs will be conducted at Visits 1, 2, 3, and 4.

The procedure of the 6MWT should be explained and demonstrated to the subject prior to the start of the test.

Sit to Stand (STS) Measurement

Intervention Type DIAGNOSTIC_TEST

The STS will be conducted at Visits 1, 2, 3, and 4 to assess the physical functioning of the adult participants.

Cohort 2

Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.

Questionnaires and Patient Reported Outcomes (PROs)

Intervention Type OTHER

* EuroQol 5 Dimensional Quality of Life Questionnaire (EQ-5D).
* St. George's Respiratory Questionnaire (SGRQ)
* Impact of Events Scale Revised (IES-R)
* Generalized Anxiety Disorder 7-Item (GAD-7)
* Patient Health Questionnaire (PHQ-9)

Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)

Intervention Type DIAGNOSTIC_TEST

If required by the local site's COVID-19 guidelines, subjects should have the COVID-19 RT-PCR Nasal Swab collected at the beginning of the visit or within 5 days prior to the scheduled visit.

Blood Samples for Biomarkers

Intervention Type GENETIC

Venous blood will be collected using pre-labeled tubes.

High Resolution Computed Tomography

Intervention Type DIAGNOSTIC_TEST

Subjects will have HRCTs at Visits 1, 2, 3, and 4. Inpatient HRCT scans will be collected during the baseline visit (V0 or V1)

Physical Exam and Vital Signs

Intervention Type DIAGNOSTIC_TEST

A complete physical exam, including height, weight, general appearance, neck, lungs, cardiovascular system, abdomen, extremities, and skin will be performed at Visit 1.A brief physical exam will be completed at subsequent visits, including weight, general appearance, lungs, cardiovascular symptoms, extremities, and other body systems pertinent to the participants health status, at the discretion of the investigator.

Blood pressure, heart rate, and oxygen saturation will be collected at all visits, prior to blood draws and after subjects have rested.

Medical Research Council Sum Score

Intervention Type DIAGNOSTIC_TEST

The Medical Research Council Sum Score (MRC-SS) is used globally to detect peripheral muscle strength and to help diagnose ICU-acquired muscle weakness. The MRC-SS ranging from 0 (complete paralysis) to 60 (normal).

Hand Grip Strength

Intervention Type DIAGNOSTIC_TEST

Each subject will have hand grip strength measured at each visit. This is being done in order to assess the maximum isometric strength of hand and forearm muscles.

Spirometry

Intervention Type DIAGNOSTIC_TEST

Spirometry will be assessed at Visits 1, 2, 3 and 4. Each site will use its own spirometry machine. Each subject should use the same machine at each visit and conduct measurements at approximately the same time. Before any testing, the maneuver should be demonstrated to the subject. The spirometry should be reviewed by the investigator.

Diffusing Capacity of Carbon Monoxide

Intervention Type DIAGNOSTIC_TEST

The site will use its own DLCO equipment for measurements at Visits, 1, 2, 3, and 4. The Single-breath DLCO maneuver will be carried out in accordance with the 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Subjects should use the same device at approximately that same time at each visit. The maneuver should be demonstrated to the subject prior to the test.

6 Minute Walk Test

Intervention Type DIAGNOSTIC_TEST

The 6 Minute Walk Test (6MWT) will assess exercise capacity and tolerance. 6MWTs will be conducted at Visits 1, 2, 3, and 4.

The procedure of the 6MWT should be explained and demonstrated to the subject prior to the start of the test.

Sit to Stand (STS) Measurement

Intervention Type DIAGNOSTIC_TEST

The STS will be conducted at Visits 1, 2, 3, and 4 to assess the physical functioning of the adult participants.

Cohort 3a

Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks.

Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).

Questionnaires and Patient Reported Outcomes (PROs)

Intervention Type OTHER

* EuroQol 5 Dimensional Quality of Life Questionnaire (EQ-5D).
* St. George's Respiratory Questionnaire (SGRQ)
* Impact of Events Scale Revised (IES-R)
* Generalized Anxiety Disorder 7-Item (GAD-7)
* Patient Health Questionnaire (PHQ-9)

Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)

Intervention Type DIAGNOSTIC_TEST

If required by the local site's COVID-19 guidelines, subjects should have the COVID-19 RT-PCR Nasal Swab collected at the beginning of the visit or within 5 days prior to the scheduled visit.

Blood Samples for Biomarkers

Intervention Type GENETIC

Venous blood will be collected using pre-labeled tubes.

High Resolution Computed Tomography

Intervention Type DIAGNOSTIC_TEST

Subjects will have HRCTs at Visits 1, 2, 3, and 4. Inpatient HRCT scans will be collected during the baseline visit (V0 or V1)

Physical Exam and Vital Signs

Intervention Type DIAGNOSTIC_TEST

A complete physical exam, including height, weight, general appearance, neck, lungs, cardiovascular system, abdomen, extremities, and skin will be performed at Visit 1.A brief physical exam will be completed at subsequent visits, including weight, general appearance, lungs, cardiovascular symptoms, extremities, and other body systems pertinent to the participants health status, at the discretion of the investigator.

Blood pressure, heart rate, and oxygen saturation will be collected at all visits, prior to blood draws and after subjects have rested.

Medical Research Council Sum Score

Intervention Type DIAGNOSTIC_TEST

The Medical Research Council Sum Score (MRC-SS) is used globally to detect peripheral muscle strength and to help diagnose ICU-acquired muscle weakness. The MRC-SS ranging from 0 (complete paralysis) to 60 (normal).

Hand Grip Strength

Intervention Type DIAGNOSTIC_TEST

Each subject will have hand grip strength measured at each visit. This is being done in order to assess the maximum isometric strength of hand and forearm muscles.

Spirometry

Intervention Type DIAGNOSTIC_TEST

Spirometry will be assessed at Visits 1, 2, 3 and 4. Each site will use its own spirometry machine. Each subject should use the same machine at each visit and conduct measurements at approximately the same time. Before any testing, the maneuver should be demonstrated to the subject. The spirometry should be reviewed by the investigator.

Diffusing Capacity of Carbon Monoxide

Intervention Type DIAGNOSTIC_TEST

The site will use its own DLCO equipment for measurements at Visits, 1, 2, 3, and 4. The Single-breath DLCO maneuver will be carried out in accordance with the 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Subjects should use the same device at approximately that same time at each visit. The maneuver should be demonstrated to the subject prior to the test.

6 Minute Walk Test

Intervention Type DIAGNOSTIC_TEST

The 6 Minute Walk Test (6MWT) will assess exercise capacity and tolerance. 6MWTs will be conducted at Visits 1, 2, 3, and 4.

The procedure of the 6MWT should be explained and demonstrated to the subject prior to the start of the test.

Sit to Stand (STS) Measurement

Intervention Type DIAGNOSTIC_TEST

The STS will be conducted at Visits 1, 2, 3, and 4 to assess the physical functioning of the adult participants.

Cohort 3b

Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks.

Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.

Questionnaires and Patient Reported Outcomes (PROs)

Intervention Type OTHER

* EuroQol 5 Dimensional Quality of Life Questionnaire (EQ-5D).
* St. George's Respiratory Questionnaire (SGRQ)
* Impact of Events Scale Revised (IES-R)
* Generalized Anxiety Disorder 7-Item (GAD-7)
* Patient Health Questionnaire (PHQ-9)

Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)

Intervention Type DIAGNOSTIC_TEST

If required by the local site's COVID-19 guidelines, subjects should have the COVID-19 RT-PCR Nasal Swab collected at the beginning of the visit or within 5 days prior to the scheduled visit.

Blood Samples for Biomarkers

Intervention Type GENETIC

Venous blood will be collected using pre-labeled tubes.

High Resolution Computed Tomography

Intervention Type DIAGNOSTIC_TEST

Subjects will have HRCTs at Visits 1, 2, 3, and 4. Inpatient HRCT scans will be collected during the baseline visit (V0 or V1)

Physical Exam and Vital Signs

Intervention Type DIAGNOSTIC_TEST

A complete physical exam, including height, weight, general appearance, neck, lungs, cardiovascular system, abdomen, extremities, and skin will be performed at Visit 1.A brief physical exam will be completed at subsequent visits, including weight, general appearance, lungs, cardiovascular symptoms, extremities, and other body systems pertinent to the participants health status, at the discretion of the investigator.

Blood pressure, heart rate, and oxygen saturation will be collected at all visits, prior to blood draws and after subjects have rested.

Medical Research Council Sum Score

Intervention Type DIAGNOSTIC_TEST

The Medical Research Council Sum Score (MRC-SS) is used globally to detect peripheral muscle strength and to help diagnose ICU-acquired muscle weakness. The MRC-SS ranging from 0 (complete paralysis) to 60 (normal).

Hand Grip Strength

Intervention Type DIAGNOSTIC_TEST

Each subject will have hand grip strength measured at each visit. This is being done in order to assess the maximum isometric strength of hand and forearm muscles.

Spirometry

Intervention Type DIAGNOSTIC_TEST

Spirometry will be assessed at Visits 1, 2, 3 and 4. Each site will use its own spirometry machine. Each subject should use the same machine at each visit and conduct measurements at approximately the same time. Before any testing, the maneuver should be demonstrated to the subject. The spirometry should be reviewed by the investigator.

Diffusing Capacity of Carbon Monoxide

Intervention Type DIAGNOSTIC_TEST

The site will use its own DLCO equipment for measurements at Visits, 1, 2, 3, and 4. The Single-breath DLCO maneuver will be carried out in accordance with the 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Subjects should use the same device at approximately that same time at each visit. The maneuver should be demonstrated to the subject prior to the test.

6 Minute Walk Test

Intervention Type DIAGNOSTIC_TEST

The 6 Minute Walk Test (6MWT) will assess exercise capacity and tolerance. 6MWTs will be conducted at Visits 1, 2, 3, and 4.

The procedure of the 6MWT should be explained and demonstrated to the subject prior to the start of the test.

Sit to Stand (STS) Measurement

Intervention Type DIAGNOSTIC_TEST

The STS will be conducted at Visits 1, 2, 3, and 4 to assess the physical functioning of the adult participants.

Interventions

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Questionnaires and Patient Reported Outcomes (PROs)

* EuroQol 5 Dimensional Quality of Life Questionnaire (EQ-5D).
* St. George's Respiratory Questionnaire (SGRQ)
* Impact of Events Scale Revised (IES-R)
* Generalized Anxiety Disorder 7-Item (GAD-7)
* Patient Health Questionnaire (PHQ-9)

Intervention Type OTHER

Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)

If required by the local site's COVID-19 guidelines, subjects should have the COVID-19 RT-PCR Nasal Swab collected at the beginning of the visit or within 5 days prior to the scheduled visit.

Intervention Type DIAGNOSTIC_TEST

Blood Samples for Biomarkers

Venous blood will be collected using pre-labeled tubes.

Intervention Type GENETIC

High Resolution Computed Tomography

Subjects will have HRCTs at Visits 1, 2, 3, and 4. Inpatient HRCT scans will be collected during the baseline visit (V0 or V1)

Intervention Type DIAGNOSTIC_TEST

Physical Exam and Vital Signs

A complete physical exam, including height, weight, general appearance, neck, lungs, cardiovascular system, abdomen, extremities, and skin will be performed at Visit 1.A brief physical exam will be completed at subsequent visits, including weight, general appearance, lungs, cardiovascular symptoms, extremities, and other body systems pertinent to the participants health status, at the discretion of the investigator.

Blood pressure, heart rate, and oxygen saturation will be collected at all visits, prior to blood draws and after subjects have rested.

Intervention Type DIAGNOSTIC_TEST

Medical Research Council Sum Score

The Medical Research Council Sum Score (MRC-SS) is used globally to detect peripheral muscle strength and to help diagnose ICU-acquired muscle weakness. The MRC-SS ranging from 0 (complete paralysis) to 60 (normal).

Intervention Type DIAGNOSTIC_TEST

Hand Grip Strength

Each subject will have hand grip strength measured at each visit. This is being done in order to assess the maximum isometric strength of hand and forearm muscles.

Intervention Type DIAGNOSTIC_TEST

Spirometry

Spirometry will be assessed at Visits 1, 2, 3 and 4. Each site will use its own spirometry machine. Each subject should use the same machine at each visit and conduct measurements at approximately the same time. Before any testing, the maneuver should be demonstrated to the subject. The spirometry should be reviewed by the investigator.

Intervention Type DIAGNOSTIC_TEST

Diffusing Capacity of Carbon Monoxide

The site will use its own DLCO equipment for measurements at Visits, 1, 2, 3, and 4. The Single-breath DLCO maneuver will be carried out in accordance with the 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Subjects should use the same device at approximately that same time at each visit. The maneuver should be demonstrated to the subject prior to the test.

Intervention Type DIAGNOSTIC_TEST

6 Minute Walk Test

The 6 Minute Walk Test (6MWT) will assess exercise capacity and tolerance. 6MWTs will be conducted at Visits 1, 2, 3, and 4.

The procedure of the 6MWT should be explained and demonstrated to the subject prior to the start of the test.

Intervention Type DIAGNOSTIC_TEST

Sit to Stand (STS) Measurement

The STS will be conducted at Visits 1, 2, 3, and 4 to assess the physical functioning of the adult participants.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert J Kaner, MD

Role: PRINCIPAL_INVESTIGATOR

WCM Associate Professor of Clinical Medicine Associate Attending

Craig S Conoscenti, MD

Role: PRINCIPAL_INVESTIGATOR

Boehringer Ingelheim

Nina Patel, MD

Role: PRINCIPAL_INVESTIGATOR

Boehringer Ingelheim

Locations

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Washington University of St. Louis

St Louis, Missouri, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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20-05022161

Identifier Type: -

Identifier Source: org_study_id

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