search
Back to results

Novel Experimental COVID-19 Therapies Affecting Host Response (NECTAR)

Primary Purpose

COVID-19, SARS-CoV-2 Infection, Coronavirus Infection

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TXA127
TRV027
Placebo
Fostamatinib
Sponsored by
Sean Collins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID-19 drug treatment, RAAS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  1. Hospitalized for COVID-19
  2. ≥18 years of age
  3. SARS-CoV-2 infection, documented by:

    1. a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
    2. documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team).
  4. Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy
  5. Symptoms or signs of acute COVID-19, defined as one or more of the following:

    1. cough
    2. reported or documented body temperature of 100.4 degrees Fahrenheit or greater
    3. shortness of breath
    4. chest pain
    5. infiltrates on chest imaging (x-ray, CT scan, lung ultrasound)

Exclusion criteria

  1. Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization
  2. Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission)
  3. Pregnancy
  4. Breastfeeding
  5. Prisoners
  6. End-stage renal disease (ESRD) on dialysis
  7. Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life.
  8. The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
  9. Known allergy/hypersensitivity to IMP or its excipients

The following exclusion criteria differ from the master protocol criteria:

TXA127-specific exclusion criteria(4/20/2022 Closed to Accrual):

  1. Patient unable to participate or declines participation in the TXA127/Ang(1-7) arm.
  2. History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
  3. Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
  4. Known severe renal artery stenosis.
  5. Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
  6. Randomized in another trial evaluating RAAS modulation in the prior 30 days

TRV027-specific exclusion criteria (4/20/2022 Closed to Accrual):

  1. Participants on ARBs will be excluded from this study arm.
  2. Patient unable to participate or declines participation in the TRV027 arm.
  3. History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
  4. Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
  5. Known severe renal artery stenosis.
  6. Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
  7. Randomized in another trial evaluating RAAS modulation in the prior 30 days

Fostamatinib specific exclusion criteria:

The following exclusion criteria differ from the master protocol criteria:

1. Randomized in another trial evaluating fostamatinib in the prior 30 days

Study arm exclusion criteria measured within 24 hours prior to randomization:

  1. AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN
  2. SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization
  3. ANC < 1000/mL
  4. Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx.
  5. Patient unable to participate or declines participation in the fostamatinib arm.

Sites / Locations

  • University of Alabama Birmingham
  • Chandler Regional Medical Center
  • Cedars-Sinai Medical Center
  • Stanford University
  • University of Colorado Hospital
  • Denver Health Medical Center
  • Yale University
  • University of Florida
  • Public Health Trust of Miami-Dade County, Florida - Jackson Memorial Hospital
  • Ponce de Leon Clinical Research Site
  • Emory Johns Creek
  • Emory St. Joseph's Hospital
  • Alexian Brothers Medical Center
  • AMITA Health St. Alexius Medical Center
  • Our Lady of the Lake Regional Medical Center
  • Ochsner Clinic Foundation
  • Johns Hopkins Bayview Medical Center
  • Johns Hopkins University
  • Jadestone Clinical Research, LLC
  • Beth Israel Deaconess Medical Center
  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Newton-Wellesley Hospital
  • Baystate Health
  • Hennepin County Medical Center
  • Washington University
  • University of Nebraska Medical Center
  • University of New Mexico Health Sciences Center
  • Montefiore Medical Center Weiler Campus
  • Montefiore Medical Center Moses Campus
  • Mount Sinai Hospital
  • Columbia University Irving Medical Center
  • University of North Carolina Medical Center
  • Wake Forest University Health Sciences
  • Cleveland Clinic Akron General
  • University of Cincinnati
  • Cleveland Clinic Fairview Hospital
  • Cleveland Clinic Foundation
  • West Chester Hospital
  • Oregon Health & Science University
  • Temple University Hospital
  • University of Pittsburgh
  • Medical University of South Carolina
  • Vanderbilt University Medical Center
  • University of Texas, Houston
  • Intermountain Medical Center
  • University of Utah Health
  • UVA Health
  • Sentara Norfolk General Hospital
  • VCU Health
  • Harborview Medical Center/University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

TXA127 (4/20/2022 Arm Closed to Accrual)

TRV027 (4/20/2022 Arm Closed to Accrual)

Placebo

Fostamatinib

Arm Description

An investigational peptide agonist of Mas receptors.

An investigational peptide biased agonist of the AT1 receptor.

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.

An investigational oral spleen tyrosine kinase inhibitor.

Outcomes

Primary Outcome Measures

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. 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

In-hospital mortality
Proportion of patients who die during hospitalization
Alive and oxygen free at Day 14
Proportion 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
Proportion 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
Proportion of patients alive free of new invasive mechanical ventilation at day 28
28-day mortality
Proportion of patients alive at Day 28
60-day mortality
Proportion of patients alive at Day 60
90-day mortality
Proportion of patients alive at Day 90
Clinical status assessed using World Health Organization (WHO) 8-point ordinal scale at Day 14
Ambulatory - Not hospitalized and no limitation of activities Ambulatory - Not hospitalized with limitation of activities or home oxygen use Hospitalized Mild Disease - Hospitalized, no oxygen therapy Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula Hospitalized Severe Disease -Invasive mechanical ventilation Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO Dead
Clinical status assessed using WHO 8-point ordinal scale at Day 28
Ambulatory - Not hospitalized and no limitation of activities Ambulatory - Not hospitalized with limitation of activities or home oxygen use Hospitalized Mild Disease - Hospitalized, no oxygen therapy Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula Hospitalized Severe Disease -Invasive mechanical ventilation Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO Dead
Clinical status assessed using WHO 8-point ordinal scale at Day 60
Ambulatory - Not hospitalized and no limitation of activities Ambulatory - Not hospitalized with limitation of activities or home oxygen use Hospitalized Mild Disease - Hospitalized, no oxygen therapy Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula Hospitalized Severe Disease -Invasive mechanical ventilation Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO Dead
Hospital-free days through 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
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
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.

Full Information

First Posted
June 9, 2021
Last Updated
September 27, 2023
Sponsor
Sean Collins
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04924660
Brief Title
Novel Experimental COVID-19 Therapies Affecting Host Response
Acronym
NECTAR
Official Title
CONNECTS Master Protocol for Clinical Trials Targeting Macro-, Micro-immuno-thrombosis, Vascular Hyperinflammation, and Hypercoagulability and Renin-angiotensin-aldosterone System (RAAS) in Hospitalized Patients With COVID-19 (ACTIV-4 Host Tissue)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 15, 2021 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sean Collins
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, SARS-CoV-2 Infection, Coronavirus Infection
Keywords
COVID-19 drug treatment, RAAS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomly allocated in a two-step process: 1) The participant will first be randomized in an m:1 ratio to receive an active study drug or placebo, where m represents the number of study drug arms for which the participant is eligible. 2) The participant will then be randomly assigned with equal probability to one of the study drug arms. Participants will receive the corresponding study drug or matching placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Which study drug arm the participant enters will be known to the research sites and the participants, but assignment to active versus placebo will be blinded. The randomized assignment, concealed from the research team, will be transmitted to the site pharmacy, who will provide study medication. The participant, treating clinicians, study personnel (other than the unblinded statistician who will prepare closed DSMB interim reports), and outcome assessors will all remain blinded to group assignment until after the database is locked and blinded analysis is completed.
Allocation
Randomized
Enrollment
871 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TXA127 (4/20/2022 Arm Closed to Accrual)
Arm Type
Experimental
Arm Description
An investigational peptide agonist of Mas receptors.
Arm Title
TRV027 (4/20/2022 Arm Closed to Accrual)
Arm Type
Experimental
Arm Description
An investigational peptide biased agonist of the AT1 receptor.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Fostamatinib
Arm Type
Experimental
Arm Description
An investigational oral spleen tyrosine kinase inhibitor.
Intervention Type
Drug
Intervention Name(s)
TXA127
Intervention Description
TXA127 0.5 mg/kg/day infused 3 hours daily for 5 days or until hospital discharge whichever comes first.
Intervention Type
Drug
Intervention Name(s)
TRV027
Intervention Description
TRV027 12mg/h as a continuous 24-hour infusion, infused for 5 days or until hospital discharge whichever comes first.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
NaCl 0.9% infused to match the duration of the agent (3 hours for TXA127 and continuous 24-hour infusion for TRV027, over 30 minutes for APN01. Orange film-coated, plain bioconvex tablets orally twice daily for 14 days or 28 doses for fostamatinib. Study medication will be continued as an outpatient if the patient is discharged prior to completing 28 doses.
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Intervention Description
Fostamatinib100-150mg orally twice daily for 14 days or 28 doses. Study medication will be continued as an outpatient if the patient is discharged prior to completing 28 doses.
Primary Outcome Measure Information:
Title
Oxygen free days through day 28.
Description
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).
Time Frame
Day 1 to Day 28
Secondary Outcome Measure Information:
Title
In-hospital mortality
Description
Proportion of patients who die during hospitalization
Time Frame
Day 1 to hospital discharge or Day 90 whichever comes first
Title
Alive and oxygen free at Day 14
Description
Proportion 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).
Time Frame
Day 1 to Day 14
Title
Alive and oxygen free at Day 28
Description
Proportion 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).
Time Frame
Day 1 to Day 28
Title
Alive and free of new invasive mechanical ventilation at day 28
Description
Proportion of patients alive free of new invasive mechanical ventilation at day 28
Time Frame
Day 1 to Day 28
Title
28-day mortality
Description
Proportion of patients alive at Day 28
Time Frame
Day 28
Title
60-day mortality
Description
Proportion of patients alive at Day 60
Time Frame
Day 60
Title
90-day mortality
Description
Proportion of patients alive at Day 90
Time Frame
Day 90
Title
Clinical status assessed using World Health Organization (WHO) 8-point ordinal scale at Day 14
Description
Ambulatory - Not hospitalized and no limitation of activities Ambulatory - Not hospitalized with limitation of activities or home oxygen use Hospitalized Mild Disease - Hospitalized, no oxygen therapy Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula Hospitalized Severe Disease -Invasive mechanical ventilation Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO Dead
Time Frame
Day 14
Title
Clinical status assessed using WHO 8-point ordinal scale at Day 28
Description
Ambulatory - Not hospitalized and no limitation of activities Ambulatory - Not hospitalized with limitation of activities or home oxygen use Hospitalized Mild Disease - Hospitalized, no oxygen therapy Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula Hospitalized Severe Disease -Invasive mechanical ventilation Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO Dead
Time Frame
Day 28
Title
Clinical status assessed using WHO 8-point ordinal scale at Day 60
Description
Ambulatory - Not hospitalized and no limitation of activities Ambulatory - Not hospitalized with limitation of activities or home oxygen use Hospitalized Mild Disease - Hospitalized, no oxygen therapy Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula Hospitalized Severe Disease -Invasive mechanical ventilation Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO Dead
Time Frame
Day 60
Title
Hospital-free days through day 28
Description
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.
Time Frame
Day 1 to Day 28
Title
Ventilator-free days through day 28
Description
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.
Time Frame
Day 1 to Day 28
Title
Respiratory failure-free days through day 28
Description
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.
Time Frame
Day 1 to Day 28
Other Pre-specified Outcome Measures:
Title
Renal outcomes: acute kidney Injury (when possible, at participating sites)
Description
Proportion of participants with evidence of acute kidney injury using the KDIGO Stage 2 criteria for serum creatinine relative to baseline at Day 0.
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
Myocardial injury (when possible, at participating sites)
Description
Proportion of participants with Myocardial injury described by changes in troponin before, during and after therapy during hospitalization.
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
RAAS pathway mechanistic biomarkers (when possible and applicable, at participating sites)
Description
Proportion of participants with changes in RAAS mechanistic biomarkers (AngII, Ang(1-7), ACE activity and ACE2 activity) before, during and after therapy during hospitalization.
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
Trajectories of biomarkers related to COVID-19 (when possible, at participating sites)
Description
Proportion of participants with changes in trajectories of biomarkers related to COVID-19
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
Changes in NT-proBNP (when possible, at participating sites)
Description
Proportion of participants with changes in NTproBNP before, during and after therapy during hospitalization.
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
Hypotension
Description
Proportion of participants with hypotension defined by low arterial blood pressure leading to either [1] initiation or increase in vasopressor therapy, [2] administration of a fluid bolus of 500 ml or more, or [3] modification of the dose or discontinuation of the study drug.
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
Allergic reaction
Description
Proportion of participants with allergic reaction, including rash and angioedema
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first
Title
Incident renal replacement therapy during hospitalization (when possible, at participating sites)
Description
Proportion of participants requiring renal replacement therapy
Time Frame
Day 0 to Day 5 or hospital discharge whichever comes first

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Hospitalized for COVID-19 ≥18 years of age SARS-CoV-2 infection, documented by: a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team). Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy Symptoms or signs of acute COVID-19, defined as one or more of the following: cough reported or documented body temperature of 100.4 degrees Fahrenheit or greater shortness of breath chest pain infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) Exclusion criteria Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission) Pregnancy Breastfeeding Prisoners End-stage renal disease (ESRD) on dialysis Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life. The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient Known allergy/hypersensitivity to IMP or its excipients The following exclusion criteria differ from the master protocol criteria: TXA127-specific exclusion criteria(4/20/2022 Closed to Accrual): Patient unable to participate or declines participation in the TXA127/Ang(1-7) arm. History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm) Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg. Known severe renal artery stenosis. Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis. Randomized in another trial evaluating RAAS modulation in the prior 30 days TRV027-specific exclusion criteria (4/20/2022 Closed to Accrual): Participants on ARBs will be excluded from this study arm. Patient unable to participate or declines participation in the TRV027 arm. History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm) Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg. Known severe renal artery stenosis. Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis. Randomized in another trial evaluating RAAS modulation in the prior 30 days Fostamatinib specific exclusion criteria: The following exclusion criteria differ from the master protocol criteria: 1. Randomized in another trial evaluating fostamatinib in the prior 30 days Study arm exclusion criteria measured within 24 hours prior to randomization: AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization ANC < 1000/mL Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx. Patient unable to participate or declines participation in the fostamatinib arm.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sean P. Collins, M.D.
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
Chandler Regional Medical Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Denver Health Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Public Health Trust of Miami-Dade County, Florida - Jackson Memorial Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Ponce de Leon Clinical Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Emory Johns Creek
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory St. Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Alexian Brothers Medical Center
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
AMITA Health St. Alexius Medical Center
City
Hoffman Estates
State/Province
Illinois
ZIP/Postal Code
60169
Country
United States
Facility Name
Our Lady of the Lake Regional Medical Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Jadestone Clinical Research, LLC
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20904
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02072
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Newton-Wellesley Hospital
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02462
Country
United States
Facility Name
Baystate Health
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01119
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
University of New Mexico Health Sciences Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Montefiore Medical Center Weiler Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Medical Center Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina Medical Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Cleveland Clinic Akron General
City
Akron
State/Province
Ohio
ZIP/Postal Code
44321
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Cleveland Clinic Fairview Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44111
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
West Chester Hospital
City
West Chester
State/Province
Ohio
ZIP/Postal Code
45069
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
University of Texas, Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University of Utah Health
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
UVA Health
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Sentara Norfolk General Hospital
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
VCU Health
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Harborview Medical Center/University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Novel Experimental COVID-19 Therapies Affecting Host Response

We'll reach out to this number within 24 hrs