Trial Search Results

Novel Experimental COVID-19 Therapies Affecting Host Response

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Vanderbilt University Medical Center

Collaborator: National Institutes of Health (NIH)

Stanford Investigator(s):

Intervention(s):

  • Drug: TXA127
  • Drug: TRV027
  • Drug: Placebo
  • Drug: Fostamatinib

Phase:

Phase 2/Phase 3

Eligibility


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 in the study protocol)

   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 painTXA127-specific exclusion criter

      5. infiltrates on chest imaging (x-ray, CT scan, lung ultrasound)

Exclusion criteria

   1. COVID-19 symptom onset >14 days prior to randomization

   2. Hospitalized for >72 hours prior to randomization

   3. Pregnancy

   4. Breastfeeding

   5. Prisoners

   6. End-stage renal disease (ESRD) on dialysis

   7. Patient and/or clinical team is not pursuing full medical management (if a patient has
   a Do Not Resuscitate order that precludes chest compressions in the event of a cardiac
   arrest but is otherwise pursuing full medical management, he/she is eligible for this
   trial).

   8. The treating clinician expects inability to participate in study procedures or
   participation would not be in the best interests of the patient

The following exclusion criteria differ from the master protocol criteria:

TXA127-specific exclusion criteria:

   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:

   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:

   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 requires use of strong CYP3A modulators from Table above (Clarithromycin,
   Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Saquinavir,
   Telithromycin, Troleandomycin, Carbamazepine, Efavirenz, Enzalutamide, Modafinil,
   Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, St. John's
   Wort, or Troglitazone).

   5. Patient unable to participate or declines participation in the fostamatinib arm.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Recruiting