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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04633772
Other study ID # RBR-35734p
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date August 5, 2020
Est. completion date November 1, 2021

Study information

Verified date November 2021
Source Erasme University Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 112
Est. completion date November 1, 2021
Est. primary completion date November 1, 2021
Accepts healthy volunteers No
Gender All
Age group 17 Years to 81 Years
Eligibility 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

Study Design


Intervention

Drug:
Angiotensin-(1-7)
Intravenous supplementation of Angiotensin-(1-7)
Placebo
NaCl 0.9%

Locations

Country Name City State
Brazil Hospital Eduardo de Menezes Belo Horizonte Minas Gerais
Brazil Hospital Mater Dei Belo Horizonte Minas Gerais

Sponsors (4)

Lead Sponsor Collaborator
Erasme University Hospital Angitec, Federal University of Minas Gerais, Fonds Erasme pour la Recherche Medicale

Country where clinical trial is conducted

Brazil, 

Outcome

Type Measure Description Time frame Safety issue
Primary supplemental oxygen-free days (SOFDs) 28 - x, where x = number of days on which the patient is released from supplemental oxygen therapy after start 28 days
Secondary Hospital length of stay Hospital length of stay through study completion, on average 60 days
Secondary ventilator free days composite outcome of mortality and necessity of mechanical ventilation 28 days
Secondary ICU free days number of days free from intensive care unit through study completion, on average 40 days
Secondary RAS effectors levels Ang II and Ang-(1-7) circulating levels using mass spectrometry Baseline, 3 and 24 hours after randomization and 72 hours after randomization
Secondary CT scan findings CT scan evolutions compared to baseline including findings compatible with late pulmonary fibrosis. through study completion, on average 30 days
Secondary Changes in inflammatory markers: C reactive protein C-reactive protein levels daily measurements through study completion, on average 30 days
Secondary Changes in clinical state: vasopressors usage use of vasopressors during hospitalization through study completion, on average 30 days
Secondary Chest X ray findings Chest X-ray modifications until hospital discharge through study completion, on average 30 days
Secondary Changes in inflammatory markers: chemokines pro-inflammatory chemokine levels (IL-1/IL-6) at baseline day 3 and 7 Baseline, 3 and 24 hours after randomization and 72 hours after randomization
Secondary Changes in inflammatory markers: troponin Troponin plasmatic levels Baseline, 3 and 24 hours after randomization and 72 hours after randomization
Secondary Changes in thrombotic markers: D-Dimer D-Dimer Baseline, 3 and 24 hours after randomization and 72 hours after randomization
Secondary Changes in clinical state: secondary infections Secondary infections recorded during hospitalization through study completion, on average 30 days
Secondary Changes in clinical state: deep venous thrombosis deep venous thrombosis recorded during hospitalization through study completion, on average 30 days
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