Use of Angiotensin-(1-7) in COVID-19

Free University of Brussels (ULB)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Respiratory Failure; Infection, Coronavirus

Treatments: Drug: Placebo; Drug: Angiotensin-(1-7)

Study type: Interventional

Funder types: Other

Identifiers

NCT04633772

RBR-35734p

Details and patient eligibility

About

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.

Full 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.

Enrollment: 112 patients

Sex: All

Ages: 17 to 81 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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112 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Angiotensin-(1-7)

Experimental group

Treatment:

Drug: Angiotensin-(1-7)