Oral Melatonin in Critically Ill Patients with COVID-19: A quasi-experimental pragmatic trial.
Miguel Sánchez-García, Jesús A F Tresguerres, Manuel Álvarez-González, Belén De La Hera, Virginia Puebla, Lidia Ybañez, José-Manuel Martínez-Sesmero, Antonio Blesa, Juan-Carlos Martín-Benítez, Fernando Martínez-Sagasti, Paloma González-Arenas, Sara Domingo, Cándido Pardo, Silmary Maichle, Carolina Postigo, Sara De-Miguel, María Bringas, Raquel González-Casanova, Viktor Yordanov, Alberto Delgado-Iribarren, Esther Culebras, Miguel A. Armengol-De La-Hoz, Antonio Núñez-Reiz
doi:10.22541/au.175308854.41780414/v1
Melatonin has demonstrated antioxidant, anti-inflammatory, and potential antiviral properties. Its therapeutic role in critically ill COVID-19 patients admitted to intensive care was underexplored at the start of the pandemic. We conducted a quasiexperimental, pragmatic study over 4 consecutive uninterrupted time periods alternating control groups receiving standard of care (SoC) with treatment groups receiving SoC plus high-dose oral bedtime melatonin (50-200 mg) (OBM). The primary endpoint was 90-day mortality; secondary outcomes included sequential organ failure assessment (SOFA) scores at 4, 7, 14 and 30 days and pre-defined severe adverse events (SAEs). A total of 335 of 339 consecutive patients with a predicted stay >48 hours were enrolled; 202 received OBM with SoC and 133 received SoC alone. OBM was dispensed during the second (n=162) and fourth (n=40) study periods after the first (n=40) and third (n=93) control group periods, respectively. Melatonin therapy was associated with significantly lower 90-day mortality (20.8% vs 36.1%, OR 0.46, 95% CI 0.28-0.76). Subjects receiving melatonin had lower SOFA scores on day 4 and subsequent study visits. SAEs occurred in 84 (41.6%) subjects on OBM and in 80 (60.2%) receiving SoC (risk ratio 0.68, 95% CI 0.54-0.87; p=0.001). High-dose oral melatonin was safe and associated with improved clinical outcomes. Further evaluation of melatonin and its potential antiviral effects in future epidemics is warranted.
Hosted file Figure_3_a-b-c.docx available at https://authorea.com/users/947350/articles/1317214-oral- melatonin-in-critically-ill-patients-with-covid-19-a-quasi-experimental-pragmatic-trial
Hosted file Table_1.docx available at https://authorea.com/users/947350/articles/1317214-oral-melatonin- in-critically-ill-patients-with-covid-19-a-quasi-experimental-pragmatic-trial
Hosted file Table_2.docx available at https://authorea.com/users/947350/articles/1317214-oral-melatonin- in-critically-ill-patients-with-covid-19-a-quasi-experimental-pragmatic-trial
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