A Randomized, Open-Label, Parallel Group Study of Alpha-1 Antitrypsin Therapy in Hospitalized Patients With COVID-19.

BACKGROUND: Alpha-1 antitrypsin (AAT) reduces production of several pro-inflammatory cytokines. Increased inflammatory cytokines are prominent in the hyperinflammatory state associated with severe COVID-19 infection. The study objective was to determine if administration of AAT reduced the severity of COVID-19 pneumonia in hospitalized patients. METHODS: This multi-center, randomized (1:1), open-label, pilot study was designed to investigate if AAT with standard medical treatment (SMT) could reduce the severity of COVID-19 pneumonia compared to SMT alone. Randomized patients received intravenous AAT (120mg/kg on days 1 and 8)+SMT or SMT alone. The study ran between July 29, 2020, and June 10, 2021, at six sites in Spain. The primary efficacy outcome was the proportion of subjects dying or requiring ICU admission on or before day 15 or were dependent on invasive mechanical ventilation on day 15. Several other secondary or exploratory endpoints were studied. RESULTS: Of 100 patients randomized, 85 completed the study (AAT+SMT: n=41; SMT: n=44). Demographically the groups were similar. No significant difference was observed between the treatment groups in the composite primary endpoint: 14.0% AAT+SMT versus 22% SMT (p=0.4356) nor for death (6% versus 8%); ICU admission (8% versus 14%); requiring invasive mechanical ventilation (6% versus 4%), respectively. No significant differences were seen with secondary or exploratory endpoints. CONCLUSIONS: AAT+SMT showed no significant effects on severe COVID-19 pneumonia when compared to SMT alone. Although results were not positive, testing potential therapies with a sound theoretical basis is an important step in development of therapies for emerging diseases when no treatment exists.