TABLE 3.

ANG‐(1‐7) and analogues currently tested in clinical trials

Title (study)	Purpose	Study design	Methods	Status	Phase
Angiotensin‐(1,7) treatment in COVID‐19: the ATCO trial (NCT04332666)	Evaluating the efficacy and clinical effects of treatment with ANG‐(1‐7) in patients with COVID‐19 requiring mechanical ventilation	Randomised, controlled, adaptive Phase II/III trial, single‐blinded interventional trial	60 participants with an age of minimum 18 years with COVID‐19 requiring mechanical ventilation The study consists of two phases: Phase II and III Phase II includes 20 persons. The purpose of this phase is to confirm the safety of the drug. The purpose of Phase III is to evaluate the efficacy and clinical impact of the drug In both phases, one group of 30 participants received 0.2 mcg/kg/h of the drug, intravenously, for 48 hours. The other group (30 participants) received a placebo‐drug Primary outcome: number of ventilator‐free days at day 28 Secondary outcomes: ICU free days, hospital length of stay, time to wean from mechanical ventilation, PaO2/FiO2 changes during administration of drug, incidence of deep vein thrombosis, changes in inflammatory markers, plasma levels of ANG‐II and ANG‐(1‐7), CT scan changes	Not yet recruiting	2/3
Randomized controlled trial of angiotensin 1‐7 (TXA127) for the treatment of severe COVID‐19 (NCT04401423)	Determining if treatment of TXA127 prevents AKI and multi‐organ failure in patients with severe COVID‐19	Double‐blinded, placebo‐control, randomised clinical trial	100 participants with an age of minimum 18 years with severe COVID‐19 One group receives one three‐hour dosage of TXA127 (0.5 mg/kg, intravenously) for 10 consecutive days. Another group receives one three‐hour dosage of a placebo‐drug (0.5 mg/kg, intravenously) for 10 consecutive days Primary outcome: change of serum creatinine and the number of patients requiring intubation and ventilatory support Secondary outcome: change in the number of deceased participants, number of participants requiring dialysis and vasopressors, change in blood inflammatory markers, percent change in supplemental oxygen requirements	Recruiting	2
Angiotensin (1‐7) for the treatment of COVID‐19 in hospitalised patients (NCT04570501)	Evaluating the effects of intravenous (IV) treatment of ANG‐(1‐7) for treatment of COVID‐19	Randomised, double‐blind, placebo‐controlled study.	160 participants with an age of minimum 18 years hospitalised with COVID‐19 Participants are divided into two groups. One group receives ANG‐(1‐7) treatment IV for 7 days. The other group receives a placebo drug IV for 7 days Primary outcome: time to recovery	Not yet recruiting	½
Evaluation of the possible role of angiotensin peptide (1‐7) on treatment of COVID‐19 (NCT04375124)	Evaluate the effects of plasma‐derived ANG‐(1‐7) supplementation in the treatment of COVID‐19	Interventional	20 participants (≥18 years) infected with SARS‐CoV‐2 The study population are divided into two groups. One group receives routine treatment for COVID‐19. As well as receiving routine treatment for COVID‐19, the other group receives ANG‐(1‐7) supplement Primary outcome: mortality over the period of 4 months	Recruiting	Not applicable
Angiotensin 1‐7 as a therapy for pneumonia caused by Coronavirus 2(SARS‐CoV‐2) (NCT04605887)	Treatment of COVID‐19	Double blind, randomised study	120 participants (18 years or older) with SARS‐CoV‐2 infection, fever (>37.8 ℃), cough and dyspnea 60 participants receive placebo once daily. 60 participants receive ANG‐(1‐7) subcutaneously (500 mcg/kg/day). The participants are treated in 14 days or until they are discharged from hospital Primary outcome: the need for mechanical ventilation, death	Not yet recruiting	2
Randomised clinical trial phase I/II for the use of angiotensin‐(1‐7) in the treatment of severe infection by Sars‐CoV‐2 (NCT04633772)	Determining the effects of IV ANG‐(1‐7) treatment for patients in the intensive care unit (ICU) with severe COVID‐19	Randomised controlled trial	130 participants (17 to 81 years) who have been admitted to ICU with severe pneumonia The study consists of two phases. Phase I includes 30 participants with the purpose to evaluate the safety of IV infusion of the drug Phase II includes 100 participants who are divided into two groups. One group receives ANG‐(1‐7) IV. The other group receives a placebo drug. The duration is 28 days Primary outcome: number of supplemental oxygen‐free days. Secondary outcomes: length of stay in hospital, ventilator‐free days, ICU free days, RAAS components levels, CT scan findings, changes in clinical state, chest X‐ray findings, changes in C‐reactive protein, chemokines, troponin, troponin, and D‐dimer	Recruiting	½