EFFICACY and SAFETY OF BEVACIZUMAB (ZIRABEV®) IN PATIENTS WITH SEVERE HYPOXEMIC COVID-19
Status:
Recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the most frequent
complications of the COVID-19 pandemic. In these conditions, hypoxemia may result from : i) a
pulmonary vascular dilatation resulting from an impaired hypoxic pulmonary vasoconstriction
and leading to ventilation-perfusion mismatching within the lungs and ii) thrombosis-mediated
perfusion defects. Pulmonary vascular dilation might be due to a relative failure of the
physiological acute hypoxic pulmonary vasoconstriction, in the context of an over-activation
of a regional vasodilatation cascade, as part of a dysfunctional inflammatory process.
Perfusion abnormalities associated with pulmonary vascular dilation are suggestive of
intrapulmonary shunting toward areas where gas exchange is impaired, ultimately leading to a
worsening ventilation-perfusion mismatch, a regional hypoxia and a profound hypoxemia.
Increased plasma levels of VEGF have been reported in moderate to severe COVID-19 pneumonia,
highlighting the role of VEGF in the pathophysiology of the disease. A better prognosis has
been reported in critically ill patients with lower levels of growth factors, HGF and VEGF-A
at the time of ICU admission. Recent data of the study NCT 04275414 by Pang J et al have
suggested that patients receiving a single-dose of bevacizumab have improved their oxygen
support status in 92% of cases during a 28-day follow-up period, as compared with 62% of
cases in an external cohort receiving standard care.
Correcting endothelial permeability and vasodilatation with VEGF-targeted therapy could allow
repair damaged vascular endothelium, have an indirect anti-inflammatory effect (limiting
alveolar exudation of circulating inflammatory and procoagulant mediators) and improve
oxygenation and therefore reduce the proportion of patients with severe forms requiring ICU
referral and finally patient death. This clinical trial will therefore focus on the specific
efficacy of bevacizumab in COVID-19 patients with severe hypoxemia.