Overview

The goal of this clinical trial is to find out if giving certain medications once a day works just as well as giving them twice a day to treat infections around the lungs (called pleural infections). These medications-tissue plasminogen activator (tPA) and deoxyribonuclease (DNase)-are placed through a chest tube into the space between the lung and the chest wall to help clear out the infection.

The investigators are trying to learn:

• Does using the medicine once a day work just as well as using it twice a day?
• Are there any differences in outcomes between patients who get the medicine once a day versus twice a day?
• Does more or less fluid remain in the chest (seen on a chest x-ray) depending on how often the medicine is given?

Participants will:

• Have an infection around their lung and will already be getting normal hospital care, including a chest tube to drain the infected fluid around their lung.
• Be asked to give permission to join the study.
• Be randomly chosen (like flipping a coin) to get the medications either once a day or twice a day through the chest tube.

Eligibility

Inclusion Criteria:

• Written informed consent obtained from patient or patient's legally authorized representative (LAR) to participate in the study and HIPAA authorization for release of personal health information.
• Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
• Age ≥ 18 years at the time of consent.
• Patient is admitted to the hospital and with a pleural effusion that is drained with a small-bore chest tube or one that allows for administration of IET
• Pleural fluid that is one of the following:

  (i) Macroscopically purulent or pleural fluid gram stain or culture positive for bacteria (ii) potential of hydrogen (pH) \< 7.2 (iii) Pleural fluid glucose \< 60mg/dL (iv) Pleural fluid Lactate Dehydrogenase (LDH) \> 1,000 IU/L

• Patient is deemed a candidate to receive intrapleural enzyme therapy as defined by having a residual collection or persistent sepsis 24 hours after initial chest tube placement

Exclusion Criteria:

• Known pregnancy or lactating females
• Prisoners
• Age \<18 years at time of consent
• Previous treatment with intra-pleural fibrinolytic agents, DNase, or both during the same hospital admission
• Known sensitivity or allergic reaction to DNAse or tPA
• Coincidental stroke, major hemorrhage (requiring blood transfusions within the last 5 days), major trauma, or major surgery within the last 5 days
• Previous pneumonectomy or active bronchopleural fistula on the affected side
• Therapeutic systemic anticoagulation or antiplatelet agents that cannot held for more than 48 hours prior to IET administration
• Expected survival of less than 3 months due to a pathologic condition other than that causing the pleural infection