A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions

Abstract

Aim: A double blind randomized cross over trial to compare the rate of decortication, safety and efficacy of intrapleural instillation of Alteplase vs. Placebo in empyema and complicated parapneumonic effusions (CPE).

Methods: Patients diagnosed with empyema or CPE and considered for surgery were given the option to enter into this trial. Intrapleural instillation of the 'Drug' was given daily for three days. Patient that failed the first arm of the trial were offered surgery or to cross over to the second arm. Failure was documented if pleural effusions did not improve by 50% on CT scans after three doses of the 'Drug' or if these effusions recurred within six weeks.

Results: One hundred and eight patients were evaluated and one hundred enrolled in the trial. 32 patients were excluded, 29 for noninfectious loculated effusions, two for protocol violation and one for bleeding at chest tube site. There were 17 patients with empyema and 51 patients with CPE. 58 of the 61 patients (26 crossed over) with empyema/CPE resolved with Alteplase therapy compared to 4 of the 32 patients (one crossed over) treated with Placebo (p value <0.001). None of the patients went to surgery. Adverse events with Alteplase therapy compared to Placebo were not statistically significant, with chest pain and bleeding complications being the most common.

Conclusion: Intrapleural instillation of Alteplase is significantly more effective than Placebo in patients with empyema and PPE (95% vs.12%). This study demonstrates it is safe and efficacious with minimal adverse reactions.