Acute respiratory distress syndrome (ARDS) is a common, lethal or disabling syndrome. Mortality of patients with severe ARDS is about 40%, and the incidence of chronic disability in survivors is frequent. The histologic correlate of ARDS is diffuse alveolar damage. In response to the initial injury, there is a release of potent pro-inflammatory mediators that promote infiltration of NEUTROPHILS that PLAY A CENTRAL ROLE IN ARDS. Unfortunately, there is no specific pharmacologic therapy for ARDS. Our group has previously worked with the beta1 adrenergic selective blocker METOPROLOL in acute conditions such as acute myocardial infarction. We demonstrated that the i.v. administration of metoprolol reduced myocardial infarct size in by targeting activated neutrophils. More recently, we have shown that metoprolol, and not other beta-blockers, ameliorates exacerbated inflammation by abrogating neutrophil activation, migration and NETs formation. This beneficial effect was observed in different models of exacerbated inflammation, including acute lung injury. Based on these data, we have just finished a PILOT CLINICAL TRIAL in patients with ARDS secondary to SARS-CoV-2 infection. In this small pilot trial we observed that patients randomized to metoprolol had a significant improvement in oxygenation and lower days on mechanical ventilation. We propose a phase II prospective randomized clinical trial where 350 Pt with moderate-severe ARDS recently intubated will be randomized 1:1 to i.v. metoprolol or control. Primary endpoint: composite of “survival and days free of mechanical ventilation”. This study proposes the REPURPOSING of an old drug with no commercial interest and with a vast safety experience in the past decades (including trials led by members of our consortium). The cost of i.v. metoprolol is less than 2€ per day of treatment and, if proven beneficial, will have an overt cost/effectiveness value.

Distrés
Inflamación
Ventilación Mecánica
betabloqueante
metoprolol