The Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) Study – 3: Efficacy and safety of 1mg alteplase as a starting intrapleural dose

Introduction: Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) therapy has revolutionised management of pleural infection. However, the optimal tPA dose is still unknown. The Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) study-3 aims to evaluate the efficacy and safety of a lower starting intrapleural dose of 1mg tPA (with 5mg DNase) for pleural infection. Methods: Consecutive patients with pleural infection who required intrapleural fibrinolytic therapy were treated with 1mg tPA/5mg DNase. Escalation of tPA doses were permitted at any time at the discretion of treating physicians. Results: 100 patients (22% female, mean age=60.2) received a starting dose of intrapleural 1mg tPA/5mg DNase. Most (94%) patients were successfully treated and were discharged without needing surgery. Patients received a median of 5 [IQR=3-6] doses of tPA/DNase and 6mg of tPA [median, IQR=3-8] in total. Treatment success was supported by improved pleural fluid drainage (from 238mL pre-treatment to 2013mL [IQR=1269-2863] at 72hrs, p<0.0001), reduction in serum CRP levels (by 47.5% on day 5, p<0.0001), and clearance in radiographic pleural opacities (from median 24% [IQR=15-34] of hemithorax before tPA/DNase therapy to 10% [IQR=7-15] 72 hours after the first dose of tPA/DNase, p<0.0001). In 28 (28%) patients, tPA dose was escalated due to minimal drainage and/or persistent sepsis; 26 were successfully treated and two required surgery. One (1%) patient experienced pleural bleed. Four patients with metastatic cancers were palliated during treatment for pleural infection and died. Conclusion: A starting intrapleural regimen of 1mg tPA/5mg DNase, with dose escalation as necessary, appears to be safe and effective for pleural infection.