A Parallel Group, 1:1 Randomised, Pilot Study Comparing the Clinical Efficacy and Bleeding Risk Between Low Dose and Standard Dose Intrapleural Tissue Plasminogen Activator for Adults With Pleural Infection

Background: A pilot study to assess the feasibility of a randomization trial protocol comparing low (2.5 mg) and standard (10 mg) doses of intrapleural tissue plasminogen activator (tPA) with deoxyribonucleases (DNase) in unresolved pleural infection. The proposed protocol comparing low-dose and standard doses of intrapleural tPA (with DNase) therapy will be feasible and acceptable. Methods: A single-centre, two-arm, double-blinded, randomised controlled feasibility study which includes subjects with unresolved pleural infection eligible for intrapleural tPA/DNase injection, with follow-ups till 3 months after hospital discharge. Recruited subjects will be randomised in a 1:1 ratio to receive a maximum of 6 doses of intrapleural tPA (with DNase) starting at either 2.5 or 10 mg. A clinical decision is allowed at or after the third dose of tPA to continue the assigned regimen (blinded) or convert to open-label use of 10 mg doses of tPA to complete the course based on the clinical response. Discussion: NCT05766124, ClinicalTrials.gov.