Use of Angiotensin-(1-7) in COVID-19
Condition: Infection, Coronavirus; Respiratory Failure
MeSH terms: Infections; Coronavirus Infections; Respiratory Insufficiency
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Angiotensin-(1-7); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous supplementation of Angiotensin-(1-7); NaCl 0.9%
Intervention MeSH terms: Angiotensin I (1-7)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: angiotensin-(1-7); ARDS; renin angiotensin system