| Design | Double-blind, placebo-controlled factorial RCT |
|---|---|
| Treatment | Intrapleural tissue plasminogen activator with DNase |
| Control | Placebo, t-PA alone, or DNase alone |
| Population | Patients with pleural infection |
| Follow-up | 3 months |
| Primary endpoint | Change in pleural opacity on chest radiograph at day 7 |
| Result | Pleural opacity fell by 29.5% with t-PA/DNase versus 17.2% with placebo (difference -7.9%, 95% CI -13.4 to -2.4, p=0.005). t-PA alone (-17.2%) and DNase alone (-14.7%) were no better than placebo. Surgical referral at 3 months occurred in 2 of 48 (4%) versus 8 of 51 (16%) — odds ratio 0.17 (0.03 to 0.87, p=0.03). Hospital stay was shorter. |
| Secondary endpoints | Surgical referral, length of hospital stay, mortality |
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.
The trial authors, in the published abstract
The factorial design is what makes this trial matter — it proves the combination is necessary, not merely sufficient. Giving a fibrinolytic without DNase, which still happens, is doing the half that does not work.
Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med 2011 Aug 11;365(6):518-26.