Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

Matino et al., Nutrients, doi:10.3390/nu15051285, LAC, NCT04847791

Mar 2023

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RCT 218 hospitalized patients in Italy, showing no significant differences with lactoferrin treatment. Authors note that in several previous studies showing clinical improvement, lactoferrin was given at an earlier stage of disease. Authors also note that potential benefits with the late treatment in this study could be masked by other SOC medications - corticosteroids may have masked immunomodulatory effects of lactoferrin, and there may be heparin-dependent reduction in lactoferrin antiviral activity. 800mg oral bovine lactoferrin daily.

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risk of death, 11.5% higher, RR 1.12, p = 0.85, treatment 18 of 113 (15.9%), control 15 of 105 (14.3%), day 28.

risk of death, 23.9% higher, RR 1.24, p = 0.69, treatment 16 of 113 (14.2%), control 12 of 105 (11.4%), day 14.

risk of mechanical ventilation, 44.5% higher, RR 1.45, p = 0.39, treatment 14 of 113 (12.4%), control 9 of 105 (8.6%).

risk of death/ICU, 6.2% higher, RR 1.06, p = 0.87, treatment 24 of 113 (21.2%), control 21 of 105 (20.0%).

not reaching NEWS2 ≤2 or discharge within 14 days, 33.6% higher, RR 1.34, p = 0.12, treatment 46 of 113 (40.7%), control 32 of 105 (30.5%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Matino et al., 4 Mar 2023, Double Blind Randomized Controlled Trial, placebo-controlled, Italy, peer-reviewed, 53 authors, study period January 2021 - May 2021, average treatment delay 6.0 days, trial NCT04847791 (history) (LAC).

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Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

Erica Matino, Elena Tavella, Manuela Rizzi, Gian Carlo Avanzi, Danila Azzolina, Antonio Battaglia, Paolo Becco, Mattia Bellan, Giovanni Bertinieri, Massimo Bertoletti, Giuseppe Francesco Casciaro, Luigi Mario Castello, Umberto Colageo, Donato Colangelo, Davide Comolli, Martina Costanzo, Alessandro Croce, Davide D’onghia, Francesco Della Corte, Luigi De Mitri, Valentina Dodaro, Filippo Givone, Alessia Gravina, Luca Grillenzoni, Graziano Gusmaroli, Raffaella Landi, Anna Lingua, Roberto Manzoni, Vito Marinoni, Bianca Masturzo, Rosalba Minisini, Marina Morello, Anna Nelva, Elena Ortone, Rita Paolella, Giuseppe Patti, Anita Pedrinelli, Mario Pirisi, Lidia Ravizzi, Eleonora Rizzi, Daniele Sola, Mariolina Sola, Nadir Tonello, Stelvio Tonello, Gigliola Topazzo, Aldo Tua, Piera Valenti, Rosanna Vaschetto, Veronica Vassia, Erika Zecca, Nicoletta Zublena, Paolo Manzoni, Pier Paolo Sainaghi

Nutrients, doi:10.3390/nu15051285

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and Nutrients 2023, 15, 1285. https://doi.org/10.3390/nu15051285 https://www.mdpi.com/journal/nutrients tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

Conflicts of Interest: The authors declare no conflict of interest.

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Late treatment
is less effective

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