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Pentoxifylline decreases serum LDH levels and increases lymphocyte count in COVID-19 patients: Results from an external pilot study

Maldonado et al., International Immunopharmacology, doi:10.1016/j.intimp.2020.107209, Jan 2021
https://c19early.org/maldonado2.html
Mortality 65% Improvement Relative Risk Ventilation 54% Hospitalization time 15% Pentoxifylline  Maldonado et al.  LATE TREATMENT  RCT Is late treatment with pentoxifylline beneficial for COVID-19? RCT 38 patients in Mexico (July - August 2020) Lower mortality (p=0.18) and ventilation (p=0.36), not sig. c19early.org Maldonado et al., Int. Immunopharmacol.., Jan 2021 Favorspentoxifylline Favorscontrol 0 0.5 1 1.5 2+
Pilot study of 38 hospitalized COVID-19 patients in Mexico showing pentoxifylline treatment was associated with significantly increased lymphocyte count and decreased LDH levels compared to standard care. The pentoxifylline group (400mg three times daily from admission to discharge) showed trends toward reduced days of hospitalization, lower mortality, and less need for intubation, though these differences did not reach statistical significance. Authors suggest pentoxifylline may help restore immune response equilibrium and reduce tissue damage in COVID-19 through its anti-inflammatory properties and effects on the renin-angiotensin system.
risk of death, 65.4% lower, RR 0.35, p = 0.18, treatment 3 of 26 (11.5%), control 4 of 12 (33.3%), NNT 4.6.
risk of mechanical ventilation, 53.8% lower, RR 0.46, p = 0.36, treatment 3 of 26 (11.5%), control 3 of 12 (25.0%), NNT 7.4.
hospitalization time, 14.5% lower, relative time 0.85, p = 0.33, treatment mean 11.2 (±5.5) n=26, control mean 13.1 (±5.6) n=12.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Maldonado et al., 31 Jan 2021, Randomized Controlled Trial, Mexico, peer-reviewed, median age 55.3, 9 authors, study period July 2020 - August 2020. Contact: valentemaldonado@lasallistas.org.mx.
Pentoxifylline decreases serum LDH levels and increases lymphocyte count in COVID-19 patients: Results from an external pilot study
Valente Maldonado, Claudia Hernandez-Ramírez, Eniel Alonso Oliva-Pérez, César Omar Sánchez-Martínez, Jorge Fabián Pimentel-González, José Raúl Molina-Sánchez, Yeimmy Zuyenn Jiménez-Villalba, Jaime Chávez-Alderete, Marco A Loza-Mejía
International Immunopharmacology, doi:10.1016/j.intimp.2020.107209
We have previously hypothesized that pentoxifylline could be beneficial for the treatment of COVID-19 given its potential to restore the immune response equilibrium, reduce the impact of the disease on the endothelium and alveolar epithelial cells, and improve the circulatory function. Serum lactate dehydrogenase (LDH) and lymphocyte count are accessible biomarkers that correlate with the severity of COVID-19, the need for hospitalization, and mortality, reflecting the host immune response's contribution to the seriousness of SARS-CoV-2 infection. We carried out this external pilot study on 38 patients with moderate and severe COVID-19 to test the effect pentoxifylline on parameters such as LDH, lymphocyte count, days of hospitalization, mortality, and proportion of patients requiring intubation. Twenty-six patients were randomized to receive 400 mg of pentoxifylline t.i.d. plus standard therapy (pentoxifylline group), while the rest received the standard treatment (control group). Linear regression models were built for statistically significant parameters. Pentoxifylline treatment was associated with a 64.25% increase (CI95% 11.83, 116.68) in lymphocyte count and a 29.61% decrease (CI95% 15.11, 44.10) in serum LDH. Although a trend towards reduced days of hospitalization, mortality, and proportion of patients requiring intubation was observed, no statistically significant difference was found for these parameters. Our findings open the possibility of pentoxifylline being repositioned as a drug for COVID-19 treatment with the advantages of a proven safety profile, availability, and no risk of immunosuppression; however, this evidence needs to be confirmed in a pragmatic randomized controlled trial.
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Late treatment
is less effective
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