Praveen N. Mathur, MD
Does intrapleural recombinant tissue plasminogen activator (t-PA) or recombinant human DNase, alone or in combination, improve outcomes in patients with pleural infection?
Randomized, 2 x 2 factorial, placebo-controlled trial (Second Multicenter Intrapleural Sepsis Trial [MIST2]). Current Controlled Trials ISRCTN57454527.
Blinded (patients, clinicians, and outcome assessors).*
11 centers in the UK.
210 patients ≥ 18 years of age (mean age 59 y, 72% men) who had evidence of infection and pleural fluid with pH < 7.2, macroscopic purulence, positive culture for bacterial infection, or positive Gram staining for bacteria. Exclusion criteria included stroke, major hemorrhage or trauma, past use of intrapleural fibrinolytic agents or DNase for empyema, major surgery in the past 5 days, previous pneumonectomy on infected side, pregnancy or lactation, and life expectancy < 3 months due to pathologic conditions unrelated to pleural infection.
t-PA, 10 mg, plus placebo (n = 52); DNase, 5 mg, plus placebo (n = 51); t-PA plus DNase (n = 52); or double placebo (n = 55), given intrapleurally twice daily for 3 days.
Change in area of pleural opacity (percentage of ipsilateral hemithorax with effusion on radiography) at day 7. Other outcomes included mortality, length of hospital stay, referral for thoracic surgery, and adverse events.
97% at 12 months (intention-to-treat analysis).
Results for length of hospital stay and surgical referral are in the Table. Pleural opacity at 7 days was reduced with t-PA plus DNase (difference compared with placebo −7.9%, P = 0.005) but not either drug alone. Groups did not differ for mortality at 12 months (t-PA 11%, DNase 20%, t-PA plus DNase 11%, placebo 8%, P = 0.37) or serious adverse events at hospital discharge (0% vs 4% vs 6% vs 2%, P = 0.22).
In patients with pleural infection, intrapleural tissue plasminogen activator plus DNase improved clinical outcomes more than placebo; each drug alone was not effective.
†t-PA = tissue plasminogen activator; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article.
‡Adjusted for baseline opacity and minimization criteria.
§Modified intention-to treat population (n = 193).
Mathur PN. Intrapleural t-PA plus DNase improved clinical outcomes in patients with pleural infection. Ann Intern Med. ;155:JC6–9. doi: 10.7326/0003-4819-155-12-201112200-02009
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Published: Ann Intern Med. 2011;155(12):JC6-9.
Infectious Disease, Pulmonary/Critical Care.
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