Once-daily intrapleural enzyme treatment for complicated pleural infections
Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema (ONLY ONCE)
PHASE4 · University of North Carolina, Chapel Hill · NCT07095361
This will see if giving tPA and DNase once a day through a chest tube works as well as giving them twice a day for people with complicated pleural infections.
Quick facts
| Phase | PHASE4 |
|---|---|
| Study type | Interventional |
| Enrollment | 270 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of North Carolina, Chapel Hill (other) |
| Locations | 2 sites (Chicago, Illinois and 1 other locations) |
| Trial ID | NCT07095361 on ClinicalTrials.gov |
What this trial studies
Hospitalized adults with complicated parapneumonic effusion or empyema who already have a chest tube are randomized to receive intrapleural tissue plasminogen activator (tPA) plus DNase either once daily or twice daily while continuing standard care. The enzymes are instilled through the chest tube to break down loculated infected fluid and improve drainage. Outcomes include amount of residual pleural fluid on chest x-ray, need for additional procedures, and clinical recovery measures. Key enrollment criteria require purulent or culture-positive pleural fluid or biochemical markers of infection and persistent collection or sepsis after initial drainage.
Who should consider this trial
Good fit: Adults (age ≥18) admitted with complicated parapneumonic effusion or empyema who have a chest tube in place and pleural fluid that is purulent, culture/Gram stain positive, or meets low pH/low glucose or high LDH criteria are eligible.
Not a fit: Patients without a chest tube, with non-infectious pleural effusions, or who are not candidates for intrapleural enzyme therapy are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, once-daily dosing could simplify care, reduce nursing/administrative burden, and potentially lower risks or costs while maintaining effectiveness.
How similar studies have performed: Prior randomized work (for example MIST2) showed that intrapleural tPA plus DNase improves drainage and outcomes, but once-daily versus twice-daily dosing has been less well studied.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Chicago, Illinois and 1 other locations
- Northwestern University — Chicago, Illinois, United States (RECRUITING)
- UNC Chapel Hill — Chapel Hill, North Carolina, United States (RECRUITING)
Study contacts
- Principal investigator: Jason Akulian, MD, MPH — University of North Carollina at Chapel Hill
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
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