Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema

NCT ID: NCT07095361

Last Updated: 2025-09-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2027-06-30

Brief Summary

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.

Conditions

Pleural Infection Bacterial; Pleural Infections; Pleural Infections and Inflammations; Empyema, Pleural; Empyema; Complicated Pleural Effusion/ Empyema; Pleural Effusion Associated With Pulmonary Infection; Pleural Effusion

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Once daily intrapleural enzyme therapy

Participants will receive intrapleural enzyme therapy (IET) once daily for 3 consecutive days.

Group Type: EXPERIMENTAL

Fibrinolytic once daily

Intervention Type: DRUG

tissue plasminogen activator (tPA) 10mg will be administered once a day as part of intrapleural enzyme therapy (IET) for 3 consecutive days.

DNA degradation once daily

Intervention Type: DRUG

Deoxyribonuclease (DNase) 5mg will be administered once a day as intrapleural enzyme therapy (IET) for 3 consecutive days.

Twice daily intrapleural enzyme therapy

Participants will receive intrapleural enzyme therapy (IET) twice daily for 3 consecutive days.

Group Type: ACTIVE_COMPARATOR

Fibrinolytic twice daily

Intervention Type: DRUG

tissue plasminogen activator (tPA) 10mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days.

DNA degradation twice daily

Intervention Type: DRUG

Deoxyribonuclease (DNase) 5mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days.

Interventions

Fibrinolytic once daily

tissue plasminogen activator (tPA) 10mg will be administered once a day as part of intrapleural enzyme therapy (IET) for 3 consecutive days.

Intervention Type: DRUG

Fibrinolytic twice daily

tissue plasminogen activator (tPA) 10mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days.

Intervention Type: DRUG

DNA degradation once daily

Deoxyribonuclease (DNase) 5mg will be administered once a day as intrapleural enzyme therapy (IET) for 3 consecutive days.

Intervention Type: DRUG

DNA degradation twice daily

Deoxyribonuclease (DNase) 5mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days.

Intervention Type: DRUG

Other Intervention Names

once daily lytics; tPA once daily; lytics twice daily; tPA twice daily; DNase once daily; lytics once daily; lytics twice daily; DNase twice daily

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason Akulian, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of North Carollina at Chapel Hill

Locations

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Facility Contacts

Hee Jae Choi, DO

Role: primary

heejae.choi@unchealth.unc.edu

919-966-2533

Ashley Delgado, BS

Role: backup

ashley_delgado@med.unc.edu

919-445-0367

Other Identifiers

24-1309

Identifier Type: -

Identifier Source: org_study_id