Comparing low and standard doses of tPA for pleural infections

A Pilot Study Comparing the Clinical Efficacy and Bleeding Risk Between Low Dose and Standard Dose Intrapleural Tissue Plasminogen Activator for Pleural Infection

This study is testing whether a lower dose of a medication called tPA can safely help people with serious lung infections just as well as the standard higher dose.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chinese University of Hong Kong (Academic / other)
• Locations: 2 sites (Hong Kong, Hong Kong and 1 other locations)
• Trial ID: NCT05766124 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the therapeutic and safety profiles of a reduced dose (2.5mg) versus a standard dose (10mg) of intrapleural tissue plasminogen activator (tPA) in patients with uncontrolled pleural infections. It is designed as a single-centre, two-arm, double-blinded, randomized controlled trial, with participants receiving up to six doses of tPA based on clinical response. The primary outcome measure is survival at 90 days post-treatment, with follow-up extending until 90 days after hospital discharge.

Who should consider this trial

Good fit: Ideal candidates include individuals with clinical features of uncontrolled pleural infection and incomplete drainage of pleural effusion.

Not a fit: Patients who have previously received intrapleural tPA for the current episode or have significant bleeding risks may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a safer and equally effective treatment option for patients with pleural infections.

How similar studies have performed: Previous studies, such as the MIST-2 trial, have shown success with intrapleural tPA therapy, indicating potential for this approach.

Eligibility 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.

Where this trial is running

Hong Kong, Hong Kong and 1 other locations

• Chinese University of Hong Kong — Hong Kong, Hong Kong, Hong Kong (Recruiting)
• Prince of Wales Hospital — Hong Kong, Hong Kong, Hong Kong (Recruiting)

Study contacts

• Study coordinator: Ka Pang Chan, MBChB

Conditions Pleural Infection