Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema

NCT07095361 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 24-1309
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 2

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

Keywords

Lytics; Intrapleural enzyme therapy; Once daily; lytic therapy

Outcome Measures

Primary Outcomes (1)

• IET Failure: Surgery and/or mortality at 90 days

  Measure the rate of IET failure (defined as surgery and/or mortality at 90 days) in both once daily IET and twice daily IET groups.

  90 days

Secondary Outcomes (10)

• 30 Day Mortality

  30 days

• Hospital length of stay

  90 days

• Oral Morphine Equivalents (OME)

  From enrollment until day 3 of intervention

• Change of White Blood Cell Count

  From enrollment until day 3 of intervention

• Change in C-reactive Protein (CRP) level

  From enrollment until day 3 of intervention

Study Arms (2)

Once daily intrapleural enzyme therapy

EXPERIMENTAL

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

Drug: Fibrinolytic once daily; Drug: DNA degradation once daily

Twice daily intrapleural enzyme therapy

ACTIVE COMPARATOR

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

Drug: Fibrinolytic twice daily; Drug: DNA degradation twice daily

Interventions

DNA degradation twice daily DRUG

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

Also known as: lytics twice daily, DNase twice daily

Twice daily intrapleural enzyme therapy

DNA degradation once daily DRUG

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

Also known as: DNase once daily, lytics once daily

Once daily intrapleural enzyme therapy

Fibrinolytic once daily DRUG

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

Also known as: once daily lytics, tPA once daily

Once daily intrapleural enzyme therapy

Fibrinolytic twice daily DRUG

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

Also known as: lytics twice daily, tPA twice daily

Twice daily intrapleural enzyme therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Henry Ford Health System: collaborator
• Yale University: collaborator
• Rush University Medical Center: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• Northwestern Memorial Hospital: collaborator
• University of North Carolina, Chapel Hill: lead

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

UNC Chapel Hill

Chapel Hill, North Carolina, 27514, United States

RECRUITING

MeSH Terms

Conditions

Inflammation; Empyema, Pleural; Empyema; Pleural Effusion

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Suppuration; Pleural Diseases; Respiratory Tract Diseases

Study Officials

• Jason Akulian, MD, MPH

  University of North Carollina at Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 31, 2025
• Study Start: September 11, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9/2026 and continuing for 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with University of North Carolina (UNC).

Locations

US (2)