TXA127 for the Treatment of Severe COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to determine if administration of angiotensin-(1-7) (TXA127) prevents acute kidney injury and deterioration into multi-organ failure in patients with severe COVID-19. Participants will undergo a 10-day treatment with either placebo or study drug. The drug will be administered intravenously for 3 hours once each day for 10 days consecutively.

Detailed Description
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Corona virus disease 2019 (COVID-19) has been associated with severe respiratory and multiorgan failure. Research shows that COVID-19 reduces levels of angiotensin-converting enzyme-2 (ACE-2), an enzyme that converts angiotensin II to angiotensin 1-7 (known as TXA127). COVID-19 reduces levels of ACE-2 and therefore angiotensin 1-7 and as a result, angiotensin II levels are going to be increased. Many clinical observations in COVID-19 have shown the high incidence of acute kidney injury that may be due to excessive levels of angiotensin II. The investigators hypothesize that administration of angiotensin (1-7) replaces levels of ACE-2 in COVID-19 and thereby ameliorates deterioration of multi-organ failure and specifically acute kidney injury.

Official Title
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Randomized Controlled Trial of Angiotensin 1-7 (TXA127) for the Treatment of Severe COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: TXA127
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe COVID-19: Adult patients admitted to the hospital through the Emergency Department (ED) requiring oxygen therapy (any level) to maintain oxygen saturation (SaO2) > 90% COVID positive by polymerase chain reaction (PCR) on hospital admission Hospitalized patients aged 18 years or greater Exclusion Criteria: Pre-existing chronic kidney disease New use of or change in dose of ACE-inhibitors or angiotensin receptor blocker (ARB) within the last 6 months Acute kidney injury at the time of enrollment defined as either increase pf serum creatinine by more than 50% or 0.3 mg/dL above baseline or estimated creatinine clearance (by MDRD) of less than 60 ml/min (if no baseline serum creatinine available) Pregnant and breastfeeding women Contraindicated medications: new use or change of medications from start of trial (start of an ACE inhibitor or ARB within 6 months of trial).

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
Interventional Model Description: Double-blinded, placebo-control, randomized clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TXA127<br>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). | Drug: TXA127<br>* 0.5 mg/kg per day<br>* Other names: angiotensin-(1-7);|
| Placebo Comparator: Placebo<br>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). | Drug: Placebo<br>* 0.5 mg/kg per day<br>* Other names: control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Serum Creatinine | Calculated from baseline (at enrollment) to end of study | Day 1 and Day 10 | 
| Number of Participants Requiring Intubation |  | From Day 1 to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Requiring Dialysis |  | Up to Day 10 | 
| Number of Participants Requiring a Vasopressors |  | Up to Day 10 | 
| Percent Change in Supplemental Oxygen Requirements |  | Day 1 and Day 10 | 
| Days of Hospital Stay and Drug Administration |  | Day 1 to Day 10 | 
| Cytokine Levels on the Day of Drug/TXA Administration |  | Day 1 | 
| Cytokine Levels on the Day 5 of Drug/TXA Administration |  | Day 5 | 
| Mortality |  | Day 1 to Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, multi-organ failure, acute kidney injury