Article
作者: Iacono, Marisa ; Stanek, Vanina ; Pereiro, Ana ; Crudo, Favio ; Zylberman, Vanesa ; de Miguel, Bernardo ; Caruso, Diego ; Dobarro, Martín ; Casas, Marcelo Martín ; Lebersztein, Gabriel ; Farina, Javier ; Bertetti, Anselmo ; Solari, Rubén ; Nannini, Esteban ; Teijeiro, Ricardo ; Lopardo, Gustavo ; Luciardi, Héctor Lucas ; Lambert, Sandra ; Cremona, Alberto ; Lloret, Santiago Perez ; Alzogaray, Maria Fernanda ; Muñoz, Luciana ; Scublinsky, Darío ; Sanguineti, Santiago ; Cruz, Pablo ; Cahn, Pedro ; Barcelona, Laura ; Colonna, Mariana ; Vidiella, Gabriela ; Spatz, Linus ; Sued, Omar ; Millán, Susana ; Abusamra, Lorena ; Kilstein, Yael ; Goldbaum, Fernando ; Belloso, Waldo H
BACKGROUND:passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2.
METHODS:we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984).
FINDINGS:between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported.
INTERPRETATION:Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.