Novel Experimental COVID-19 Therapies Affecting Host Response

• Status: Recruiting
• Trial end date: 2022-12-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Treatments: Angiotensin I (1-7)

Criteria

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 100.4o F or greater

3. shortness of breath

4. chest pain

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

Exclusion criteria

1. 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

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

3. Hospitalized for >72 hours prior to randomization

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. Pregnancy

6. Breastfeeding

7. Prisoners

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

9. 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).

10. Known severe renal artery stenosis

11. Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis

12. Randomized in another trial evaluating RAAS modulation in the prior 30 days

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

TRV027-specific exclusion criteria: Participants on Angiotensin receptor blockers (ARBs) will be excluded from this study arm.

TXA127-specific exclusion criteria: eGFR < 30 mL/min/1.73m2