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Alteplase + dornase alfa is a combination intrapleural enzyme therapy (IET) investigated for the treatment of pleural infections, including empyema and complicated parapneumonic effusions. Alteplase is a recombinant tissue plasminogen activator (tPA) that functions as a fibrinolytic agent by converting plasminogen to plasmin, which subsequently degrades fibrin septations within the pleural space. Dornase alfa (DNase) is a recombinant human deoxyribonuclease that cleaves extracellular DNA, thereby reducing the viscosity of infected pleural fluid. The University of North Carolina, Chapel Hill is conducting the Phase 4 ONLY ONCE clinical trial to evaluate whether a once-daily administration of this combination is as effective as the standard twice-daily regimen established by the MIST-2 trial. This application represents an off-label use of both agents, which are typically administered via a chest tube to facilitate drainage and avoid surgical intervention.
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