Use of Angiotensin-(1-7) in COVID-19
Use of Angiotensin-(1-7) in COVID-19
The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter
 host's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also
 play a key role in the modulation of the inflammatory response that characterizes the lung
 involvement. Angiotensin-(1-7) is a peptide that could be altered in COVID-19 patient and its
 supplementation may potentially helpful in this setting.
A novel Coronavirus (SARS-CoV-2) described in late 2019 in Wuhan, China, has led to a
 pandemic and to a specific coronavirus-related disease (COVID-19), which is mainly
 characterized by a respiratory involvement. While researching for a vaccine has been started,
 effective therapeutic solutions are urgently needed to face this threaten. The
 renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter
 host's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also
 play a key role in the modulation of the inflammatory response that characterizes the lung
 involvement. Angiotensin-(1-7) is a peptide that could be altered in COVID-19 patient and it
 may potentially improve respiratory function in this setting. This a randomized, controlled,
 investigator-initiated Phase I/Phase II trial is conceived to test the safety and the
 efficacy of intravenous angiotensin-(1-7) infusion in COVID-19 patients with severe pneumonia
 admitted to the intensive care unit (ICU). The first phase of the study, with a limited
 number of patients (n=30) will serve to confirm the safety of the intravenous infusion of the
 drug by observing the incidence of the adverse events (phase I, open label). In a second
 phase of the study, conducted in a double-blind manner and including a larger cohort of
 patients (n=100, Phase II), patients will be randomly assigned to receive either an
 Angiotensin-(1-7) infusion or placebo. The primary endpoint of the study will be the number
 of supplemental oxygen-free days by day 28. Secondary outcomes will include length of
 hospital stay, ICU and hospital free days, ICU and hospital mortality, need for mechanical
 ventilation, weaning time from mechanical ventilation if intubated, secondary infections,
 vasopressor needs, changes in PaO2 / FiO2, incidence of deep vein thrombosis, changes in
 inflammatory markers, plasma levels of angiotensin II and angiotensin (1-7) and radiological
 findings.
Inclusion Criteria:

 -  Admission to the Intensive Care Unit with severe pneumonia criteria (clinical signs of
 pneumonia + one of the following criteria: respiratory rate greater than 30/minute;
 signs of respiratory effort, SatO2 < 90% in room air);

 -  COVID-19 confirmed or highly suspicious (positive contact or suggestive image)

 Exclusion Criteria:

 -  Diagnosed with cancer (at any stage);

 -  Hemodynamic instability (need for vasopressors);

 -  Pregnant women; Immunocompromised patients;

 -  Palliative Care;

 -  Inclusion in any other interventionist study;

 -  Heart failure as a predominant cause of acute respiratory failure;

 -  Decompensated liver cirrhosis;

 -  HIV +;

 -  Dialysis;

 -  Home / long-term oxygen therapy;

 -  Idiopathic pulmonary fibrosis