A Parallel Group, 1:1 Randomised, Pilot Study Comparing the Clinical Efficacy and Bleeding Risk Between Low Dose and...

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.

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.

The main outcome is the feasibility of the trial protocol, based on the percentage of eligible patients enrolled, retained to discharge, and completing 3 months of follow-up. Other important outcomes include survival at 3 months follow-up and without the need for surgical intervention, the need for additional pleural interventions, the number of decisions to convert to open-labelled use of 10 mg intrapleural tPA, clinical and radiographic response after the treatment course, safety profiles, especially bleeding complications and the number and reason for protocol violation. Feasibility outcomes will be reported as descriptive data. Comparison of outcomes between the two treatment groups will be analysed on an intention-to-treat basis. Safety outcomes will be reported descriptively for each group. The reported estimates of recruitment rates, adherence, follow-up completeness, and variability and event rates for key clinical and bleeding outcomes will inform the design of future studies that incorporate the current study design. Trial registration: NCT05766124, ClinicalTrials.gov.