Author Identifier (ORCID)
Abstract
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.
Keywords
deoxyribonuclease, empyema, fibrinolytics, pleural, tissue plasminogen activator
Document Type
Journal Article
Date of Publication
1-1-2026
E-ISSN
19382650
ISSN
00015547
PubMed ID
42441530
Publication Title
Respiration
Publisher
Karger
School
School of Medical and Health Sciences
Funding Information
Y.C.G.L. is a National Health & Medical Research Council (NHMRC) Leadership Fellow. He receives funding from the NHMRC and from the Future Health Research & Innovation Fund.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
First Page
1
Last Page
9
Recommended Citation
Lau, E. P., Donaghy, M., Faber, S., Krivinskas, S., Piccolo, F., Sidhu, C., D'Orsogna, T., Vekaria, S., Fysh, E., & Lee, Y. G. (2026). The Alteplase Dose Assessment for Pleural Infection Therapy (ADAPT) study-3: Efficacy and safety of 1 mg Alteplase as a starting intrapleural dose. Respiration. Advance online publication. https://doi.org/10.1159/000553096