Angiotensin (1-7) for the Treatment of COVID-19 in Hospitalized Patients

Study Overview
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Brief Summary
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The primary objective is to evaluate the safety and efficacy of intravenous (IV) infusion of Ang (1-7) compared to placebo with respect to time to recovery, disease severity, need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO), and mortality in patients with COVID 19.

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) for the Treatment of COVID-19 in Hospitalized Patients

Conditions
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Covid19

Intervention / Treatment
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* Drug: Angiotensin-(1-7)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signs and symptoms suggestive of COVID-19 infection including cough or dyspnea Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) test ≤7 days before randomization Currently hospitalized or in an emergency department with planned hospitalization Peripheral capillary oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) <300 at Screening Exclusion Criteria: Simultaneous participation in any other clinical study incompatible with this one Treatment with an antibody immunotherapy that is not standard of care for COVID-19 within 4 weeks of Screening Requirement for mechanical ventilation or ECMO at Screening Hypotension at Screening, defined as supine BP <95 mm Hg systolic or <55 mm Hg diastolic Severe liver injury defined as AST or ALT ≥5x the upper limit of normal Severe kidney failure defined as an estimated glomerular filtration rate (eGFR) <30 mL/min Any known immune deficiency Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Angiotensin (1-7)<br>Participants receive treatment for 7 days. | Drug: Angiotensin-(1-7)<br>* Ang (1-7) administered by continuous intravenous (IV) infusion<br>|
| Placebo Comparator: Placebo<br>Participants receive treatment for 7 days. | Drug: Placebo<br>* Placebo (normal saline) administered by continuous intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery | Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities | Up to 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of mortality at Day 29 |  | 29 days | 
| Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose |  | Up to 29 days | 
| Number of participants requiring mechanical ventilation or ECMO, or dying, through Day 29 |  | Up to 29 days | 
| COVID-19 disease severity scale score on Day 8 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 8 | 
| COVID-19 disease severity scale score on Day 15 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 15 | 
| COVID-19 disease severity scale score on Day 22 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 22 | 
| COVID-19 disease severity scale score on Day 29 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 29 |