Streptokinase did not reduce mortality or need for surgical drainage in pleural infection.

M e t h o d s Design: Randomized placebo-controlled trial (First Multicenter Intrapleural Sepsis Trial [MIST1]). Allocation: Concealed.* Blinding: Blinded (clinicians, patients, and outcome assessors).* Follow-up period: 12 months. Setting: 52 centers in the United Kingdom. Patients: 454 patients with macroscopically purulent pleural fluid or fluid that had a positive culture for bacterial infection, was positive for bacteria on Gram staining, or had pH < 7.2 and clinical evidence of infection. Exclusion criteria included age < 18 years; concomitant serious illness; previous intrapleural fibrinolytic therapy for this empyema; previous video-assisted thoracic drainage, thoracotomy, pleural decortication, or open surgical drainage for this empyema; major surgery in the past 5 days; and pregnancy or lactation. Intervention: Streptokinase, 250 000 IU (Streptase, Aventis, UK) (n = 208), or placebo (n = 222) in 30 mL of normal saline delivered through the chest tube into the pleural space every 12 hours for 6 doses. All patients received chest-tube drainage and antibiotics. Outcomes: A composite endpoint of death or need for surgical drainage of the infected pleural fluid at 3 months. Secondary outcomes included the composite endpoint at 12 months, the individual components of the composite endpoint, and hospital length of stay. The study had 80% power to detect a 40% reduction in the primary outcome with streptokinase. Patient follow-up: 430 patients (95%) (mean age 61 y, 70% men). Primary outcome data were available for 427 patients (94%).