Rationale: Pleural infection is frequently encountered in clinical practice and is associated with high morbidity and mortality. Limited evidence exists regarding the optimal treatment. Although both early medical thoracoscopy (MT) and tube thoracostomy with intrapleural instillation of tissue plasminogen activator and human recombinant deoxyribonuclease are acceptable treatments for patients with complicated pleural infection, there is a lack of comparative data for these modes of management.Objectives: The aim of this study was to compare the safety and efficacy of early MT versus intrapleural fibrinolytic therapy (IPFT) in selected patients with multiloculated pleural infection and empyema.Methods: This was a prospective multicenter, randomized controlled trial involving patients who underwent MT or IPFT for pleural infection. The primary outcome was the length of hospital stay after either intervention. Secondary outcomes included the total length of hospital stay, treatment failure, 30-day mortality, and adverse events.Results: Thirty-two patients with pleural infection were included in the study. The median length of stay after an intervention was 4 days in the IPFT arm and 2 days in the MT arm (P = 0.026). The total length of hospital stay was 6 days in the IPFT arm and 3.5 days in MT arm (P = 0.12). There was no difference in treatment failure, mortality, or adverse events between the treatment groups, and no serious complications related to either intervention were recorded.Conclusions: When used early in the course of a complicated parapneumonic effusion or empyema, MT is safe and might shorten hospital stays for selected patients as compared with IPFT therapy. A multicenter trial with a larger sample size is needed to confirm these findings.Clinical trial registered with ClinicalTrials.gov (NCT02973139).

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