Novel Experimental COVID-19 Therapies Affecting Host Response
- Conditions
- COVID-19SARS-CoV-2 InfectionCoronavirus Infection
- Interventions
- Registration Number
- NCT04924660
- Lead Sponsor
- Sean Collins
- Brief Summary
The overarching goal of the Master Protocol is to find effective strategies for inpatient management of patients with COVID-19. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19. The primary analysis will include data from NCT05593770.
- Detailed Description
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. The clinical spectrum of COVID-19 infection is broad, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and death. Between 13 and 40% of patients become hospitalized, up to 30% of those hospitalized require admission for intensive care, and there is a 13% inpatient mortality rate. The reasons for hospitalization include respiratory support, as well as support for failure of other organs, including the heart and kidneys. The risk of thrombotic complications is increased, even when compared to other viral respiratory illnesses, such as influenza. While 82% of hospitalized patients with COVID-19 are ultimately discharged alive, median length of stay is 10-13 days.
Early work in treating COVID-19 has focused on preventing worsening of the initial clinical presentation to prevent hospitalization and disease progression to organ failure and death. Studies conducted under this Master Host Tissue Protocol are expected to extend our knowledge of how to manage patients who are hospitalized for COVID-19 illness. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19. This Master Protocol is a randomized, placebo-controlled trial of agents targeting the host response in COVID-19 in hospitalized patients with hypoxemia. The Master Host Tissue Protocol is designed to be flexible in the number of study arms, the use of a single placebo group, and the stopping and adding of new therapies. Our primary outcome is oxygen free days through day 28. This is defined as days alive and without supplemental oxygen use during the first 28 days following randomization. Patients who die on or before day 28 are assigned -1 oxygen free days.
April 20, 2022 TRV027 and TXA127 arms closed to accrual.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1060
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TXA127 (4/20/2022 Arm Closed to Accrual) TXA127 An investigational peptide agonist of Mas receptors. Placebo Placebo NaCl 0.9% infused to match the duration of the agent for TXA127, TRV027, and APN01. Orange film-coated, plain, bioconvex tablets for fostamatinib. For the purposes of interim and final analyses, the route and frequency of placebo will be ignored, and all placebo participants will be pooled together as a single group. In comparing an active drug versus placebo, only those placebo participants that were eligible for the active drug will be included. TRV027 (4/20/2022 Arm Closed to Accrual) TRV027 An investigational peptide biased agonist of the AT1 receptor. Fostamatinib Fostamatinib An investigational oral spleen tyrosine kinase inhibitor.
- Primary Outcome Measures
Name Time Method Oxygen Free Days Through Day 28. Day 1 to Day 28 This is defined as days alive and without supplemental oxygen use during the first 28 days following randomization. Patients who die on or before day 28 are assigned -1 oxygen free days. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
- Secondary Outcome Measures
Name Time Method Clinical Status Assessed Using WHO 8-point Ordinal Scale at Day 60 Day 60 Number of participants who fell within the ordinal scale per the below criteria. Each row represents the country and number of participants with the score in numerical order.
1. Ambulatory - Not hospitalized and no limitation of activities
2. Ambulatory - Not hospitalized with limitation of activities or home oxygen use
3. Hospitalized Mild Disease - Hospitalized, no oxygen therapy
4. Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs
5. Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula
6. Hospitalized Severe Disease -Invasive mechanical ventilation
7. Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO
8. DeadHospital-free Days Through Day 28 Day 1 to Day 28 Days alive and not hospitalized during the first 28 days following randomization. Patients who die on or before day 28 are assigned a value -1.
Ventilator-free Days Through Day 28 Day 1 to Day 28 Days alive and not receiving mechanical ventilation during the first 28 days following randomization. Patients who die on or before day 28 are assigned a value -1.
Respiratory Failure-free Days Through Day 28 Day 1 to Day 28 Days alive and not in respiratory failure during the first 28 days following randomization. A respiratory failure-free day is defined as a day alive without the use of HFNC, NIV, IMV, or (ECMO). Patients who die on or before day 28 are assigned a value -1.
In-hospital Mortality Day 1 to hospital discharge or Day 90 whichever comes first Number of patients who die during hospitalization
Alive and Oxygen Free at Day 14 Day 1 to Day 14 Number of patients oxygen free at day 14. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
Alive and Oxygen Free at Day 28 Day 1 to Day 28 Number of patients oxygen-free at day 28. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
Alive and Free of New Invasive Mechanical Ventilation at Day 28 Day 1 to Day 28 Number of patients alive free of new invasive mechanical ventilation at day 28
28-day Mortality Day 28 Number of patients who have died at Day 28
60-day Mortality Day 60 Number of patients who have died at Day 60
90-day Mortality Day 90 Number of patients who have died at Day 90
Clinical Status Assessed Using World Health Organization(WHO) 8-point Ordinal Scale Day 14 Number of participants who fell within the ordinal scale per the below criteria. Each row represents the country and number of participants with the score in numerical order.
1. Ambulatory - Not hospitalized and no limitation of activities
2. Ambulatory - Not hospitalized with limitation of activities or home oxygen use
3. Hospitalized Mild Disease - Hospitalized, no oxygen therapy
4. Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs
5. Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula
6. Hospitalized Severe Disease -Invasive mechanical ventilation
7. Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO
8. DeadClinical Status Assessed Using WHO 8-point Ordinal Scale at Day 28 Day 28 Number of participants who fell within the ordinal scale per the below criteria. Each row represents the country and number of participants with the score in numerical order.
1. Ambulatory - Not hospitalized and no limitation of activities
2. Ambulatory - Not hospitalized with limitation of activities or home oxygen use
3. Hospitalized Mild Disease - Hospitalized, no oxygen therapy
4. Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs
5. Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula
6. Hospitalized Severe Disease -Invasive mechanical ventilation
7. Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO
8. Dead
Trial Locations
- Locations (51)
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Chandler Regional Medical Center
🇺🇸Chandler, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Stanford, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Denver Health Medical Center
🇺🇸Denver, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Public Health Trust of Miami-Dade County, Florida - Jackson Memorial Hospital
🇺🇸Miami, Florida, United States
Ponce de Leon Clinical Research Site
🇺🇸Atlanta, Georgia, United States
Scroll for more (41 remaining)University of Alabama Birmingham🇺🇸Birmingham, Alabama, United States