The Alteplase Dose Assessment for Pleural Infection Therapy (ADAPT) Study-3: Efficacy and Safety of 1 mg 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 1 mg tPA (with 5 mg DNase) for pleural infection. METHODS: Consecutive patients with pleural infection who required intrapleural fibrinolytic therapy were treated with 1 mg tPA/5 mg DNase. Escalation of tPA doses were permitted at any time at the discretion of treating physicians. RESULTS: A total of 100 patients (22% female, mean age = 60.2) received a starting dose of intrapleural 1 mg tPA/5 mg 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 6 mg of tPA [median, IQR = 3-8] in total. Treatment success was supported by improved pleural fluid drainage (from 238 mL pre-treatment to 2013 mL [IQR = 1,269-2,863] at 72 h, p < 0.0001), reduction in serum C-reactive protein 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 h 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 2 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 1 mg tPA/5 mg DNase, with dose escalation as necessary, appears to be safe and effective for pleural infection.