Comparison of Outcomes Between Low and Standard Dose Intrapleural tPA for Pleural Infection

• Status: Not yet recruiting
• Trial end date: 2027-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Objectives: A pilot study to compare the therapeutic and safety profiles between low(2.5mg) and standard(10mg) doses of intrapleural tissue plasminogen activator(tPA) in uncontrolled pleural infection. The study design will be tested for its trialability.

Hypothesis: 2.5mg tPA has comparable therapeutic efficacy and less bleeding complications to 10mg tPA.

Design and subjects: A pilot, single-centre, two-arm, double-blinded, randomized controlled trial(RCT) which includes subjects with uncontrolled pleural infection, with follow-up till 90 days after hospital discharge.

Interventions: Recruited subjects will be randomized in 1:1 ratio to receive a maximum of 6 doses of intrapleural tPA starting at either 2.5mg or 10mg. A clinical decision is allowed at the third dose to continue with the assigned dose or escalate to 10mg to complete the course based on the clinical response, without breaking the blinding.

Main outcome measures: The primary outcome is survival at 90 days and without the need for surgical intervention. Secondary outcomes include the need for additional pleural interventions, number of decisions to choose 10mg intrapleural tPA at the third dose, clinical and radiographic response after the treatment course, safety profiles especially bleeding complications, and the number and reason for protocol violation.

Data analysis and expected results: Data will be analyzed on an intention-to-treat basis for all randomized subjects. The clinical outcomes will be compared with a regression model built to adjust for confounding covariates. The data on therapeutic efficacy and bleeding complications will inform the power calculation of sample size in subsequent full-scale multicentred RCT incorporating the current study design.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chinese University of Hong Kong
• Treatments: Plasminogen; Tissue Plasminogen Activator

Criteria

Inclusion Criteria:

• Clinical features suggesting uncontrolled pleural infection with incomplete drainage of pleural effusion, at least 1 day after insertion of pleural drain (French size 12 or above) and administration of antibiotics.

• Intend to administer intrapleural fibrinolytic

• Written informed consent obtained

Exclusion Criteria:

• Previously received intrapleural tPA to the ipsilateral pleural space for the current episode of pleural infection.

• Known sensitivity to tPA or DNase.

• A coincidental stroke, major haemorrhage or major trauma.

• Frank bleeding or evidence of puncture to the intercostal artery during chest drain insertion.

• Ongoing frank bleeding from the ipsilateral pleural space.

• Has had puncture of a non-compressible vessel in the previous 14 days.

• Has had major surgery in the previous 14 days.

• Has had unprovoked gastrointestinal bleeding or intracranial haemorrhage in the last 3 months.

• Active use of anticoagulation (except prophylaxis for deep vein thrombosis) or dual-antiplatelet agents.

• Active use of any systemic fibrinolytic therapy or any airway DNase therapy.

• On long-term macrolide antibiotics (as they may interact with DNase).

• Uncorrectable bleeding diathesis or baseline INR > 1.5.

• Has had a previous pneumonectomy (either on the same or contralateral side).

• Presence of active bronchopleural fistula.

• Age less than 18 years old.

• Patients who are pregnant or lactating (females of childbearing potential must have a negative pregnancy test before randomisation).

• Expected survival less than three months from a different pathology to this empyema (e.g. metastatic lung carcinoma).

• Use of agents under research or not registered in the 30 days prior to the study.

• Inability to give informed consent.