Novel Experimental COVID-19 Therapies Affecting Host Response

Exclusion Criteria

• •1. Onset of COVID-19 symptom fulfilling inclusion criterion #5 \>14 days prior to randomization
• •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
• •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
• •1\. Randomized in another trial evaluating fostamatinib in the prior 30 days
• •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.