Clinical trial NCT04401423: TXA127 for the Treatment of Severe COVID-19
Official title: Randomized Controlled Trial of Angiotensin 1-7 (TXA127) for the Treatment of Severe COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
multi-organ failure
acute kidney injury
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Constant Therapeutics LLC
First posted: 2020-05-26
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded, placebo-control, randomized clinical trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change of Serum Creatinine
timeFrame: Day 1 and Day 10
measure: Number of Participants Requiring Intubation
timeFrame: From Day 1 to Day 10
Secondary outcomes:
measure: Number of Participants Requiring Dialysis
timeFrame: Up to Day 10
measure: Number of Participants Requiring a Vasopressors
timeFrame: Up to Day 10
measure: Percent Change in Supplemental Oxygen Requirements
timeFrame: Day 1 and Day 10
measure: Days of Hospital Stay and Drug Administration
timeFrame: Day 1 to Day 10
measure: Cytokine Levels on the Day of Drug/TXA Administration
timeFrame: Day 1
measure: Cytokine Levels on the Day 5 of Drug/TXA Administration
timeFrame: Day 5
measure: Mortality
timeFrame: Day 1 to Day 10
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Associate Professor of Medicine in Anesthesiology
name: Jeanine D'Armiento, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.