TY - JOUR
T1 - Intrapleural use of tissue plasminogen activator and DNase in pleural infection
AU - Rahman, Najib M.
AU - Maskell, Nicholas A.
AU - West, Alex
AU - Teoh, Richard
AU - Arnold, Anthony
AU - Mackinlay, Carolyn
AU - Peckham, Daniel
AU - Davies, Chris W H
AU - Ali, Nabeel
AU - Kinnear, William
AU - Bentley, Andrew
AU - Kahan, Brennan C.
AU - Wrightson, John M.
AU - Davies, Helen E.
AU - Hooper, Clare E.
AU - Lee, Y. C Gary
AU - Hedley, Emma L.
AU - Crosthwaite, Nicky
AU - Choo, Louise
AU - Helm, Emma J.
AU - Gleeson, Fergus V.
AU - Nunn, Andrew J.
AU - Davies, Robert J O
PY - 2011/8/11
Y1 - 2011/8/11
N2 - BACKGROUND: More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial. METHODS: We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. RESULTS: The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group thanin the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidenceinterval [CI], -13.4 to -2.4; P = 0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly differentfrom that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P = 0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. CONCLUSIONS: Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.)
AB - BACKGROUND: More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial. METHODS: We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. RESULTS: The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group thanin the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidenceinterval [CI], -13.4 to -2.4; P = 0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly differentfrom that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P = 0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. CONCLUSIONS: Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.)
UR - http://www.scopus.com/inward/record.url?scp=80051618075&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1012740
DO - 10.1056/NEJMoa1012740
M3 - Article
C2 - 21830966
AN - SCOPUS:80051618075
SN - 0028-4793
VL - 365
SP - 518
EP - 526
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 6
ER -