Livingston MH, Mahant S, Connolly B, et al. - A randomized clinical trial was designed to ascertain if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema. A sum of 379 children were evaluated for eligibility; 281 were eliminated and 98 were randomized. After randomization, one child was eliminated for not meeting the inclusion criteria. Between March 4, 2013, and December 13, 2017, data were collected. Compared with tPA with placebo, the addition of DNase to intrapleural tPA for children with pleural empyema had no impact on hospital length of stay or other results. For pediatric empyema, the results demonstrated that clinical practice guidelines should continue to encourage the use of chest tube insertion and intrapleural fibrinolytic alone as first-line treatment.