Effectiveness of Pentoxifylline in Adult Patients with COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Fatemeh Saghafi, Behrooz Heydari, Shima Motevali Haghighi, Amin Salehi-Abargouei, Seyedeh Mahla Hoseini, Ali Akrami, Adeleh SahebnasaghBackground:
COVID-19 is characterized by immune dysregulation, endothelial dysfunction, and thrombo-inflammation. Pentoxifylline (PTX) has been proposed as an adjunctive modality for COVID-19. Regarding the inconsistent results of earlier trials, this systematic review was conducted to evaluate the efficacy of PTX in COVID-19 patients.
Methods:
For the study literature up to 16 September 2025 was systematically searched for randomized controlled trials evaluating pentoxifylline in COVID-19. Continuous outcomes were expressed as Mean Differences (MDs) or Standardized Mean Differences (SMDs), whereas dichotomous outcomes were expressed as Odds Ratios (ORs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2.0 tool.
Results:
Seven randomized trials (551 participants) were included. Pentoxifylline significantly improved oxygen saturation (SMD = 0.215; 95% CI: 0.016 to 0.415; P = 0.034) and was associated with reduced ICU admission (OR = 0.454; 95% CI: 0.224 to 0.917; P = 0.028). It also significantly reduced inflammatory markers, including CRP and ESR. Effects on mortality, mechanical ventilation requirement, and hospital length of stay were not statistically significant. Risk-of-bias assessments indicated generally low methodological concerns, with minor issues related to blinding. Publication bias could not be reliably assessed for several outcomes because of the small number of included studies.
Conclusion:
The results of the present study suggest that pentoxifylline may reduce systemic inflammation and improve oxygenation in hospitalized adults with COVID-19. It may also be associated with reduced ICU admission; however, its effects on mortality, mechanical ventilation requirement, and hospital length of stay remain uncertain. Larger, rigorously designed randomized trials are needed to confirm these findings.