TXA127 for the Treatment of Severe COVID-19

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: TXA127; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TXA127; 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; 0.5 mg/kg per day; Other Names: angiotensin-(1-7)
Placebo Comparator: Placebo; 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; 0.5 mg/kg per day; Other Names: control

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Constant Therapeutics LLC
• Investigators: Principal Investigator: Jeanine D'Armiento, MD, PhD, Associate Professor of Medicine in Anesthesiology

Publications and helpful links

General Publications

• Wagener G, Goldklang MP, Gerber A, Elisman K, Eiseman KA, Fonseca LD, D'Armiento JM. A randomized, placebo-controlled, double-blinded pilot study of angiotensin 1-7 (TXA-127) for the treatment of severe COVID-19. Crit Care. 2022 Jul 28;26(1):229. doi: 10.1186/s13054-022-04096-9. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Actual): June 10, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; acute kidney injury; multi-organ failure
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Antihypertensive Agents; Vasodilator Agents; Angiotensin I (1-7)
• Other Study ID Numbers: AAAT0535

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No