Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07095361

Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema

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.

Recruiting

Interested in participating?

Request Info

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Yale New Haven Hospital, New Haven, Connecticut, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: once daily lytics, tPA once daily

Fibrinolytic twice daily

Drug

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

Other names: lytics twice daily, tPA twice daily

DNA degradation once daily

Drug

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

Other names: DNase once daily, lytics once daily

DNA degradation twice daily

Drug

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

Other names: lytics twice daily, DNase twice daily

Primary outcomes

  1. IET Failure: Surgery and/or mortality at 90 days

    Time frame: 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.

Secondary outcomes

  1. 30 Day Mortality

    Time frame: 30 days

    Evaluate rate of mortality at 30 days between the participants receiving once daily IET and twice daily IET

  2. Hospital length of stay

    Time frame: 90 days

    Evaluate length of hospitalization stay between the participants receiving once daily IET and twice daily IET

  3. Oral Morphine Equivalents (OME)

    Time frame: From enrollment until day 3 of intervention

    Evaluate the difference in amount of oral morphine equivalents, which is a standardized method of reporting narcotic analgesic administration by converting opioid narcotics as determined by morphine milligram equivalents (MME) that would yield same result, for daily pain between once daily IET and twice daily IET.

  4. Change of White Blood Cell Count

    Time frame: From enrollment until day 3 of intervention

    Evaluate the difference between white blood cell (WBC) count in units of cells per microliter (cells/μL) between once daily IET and twice daily IET.

  5. Change in C-reactive Protein (CRP) level

    Time frame: From enrollment until day 3 of intervention

    Evaluate the difference between C-reactive protein (CRP) level, in milligrams per liter (mg/L) or milligrams per deciliter (mg/dL), between once daily IET and twice daily IET.

  6. Change in Fever

    Time frame: From enrollment until day 3 of intervention

    Evaluate the difference between fever (in Celsius) between once daily IET and twice daily IET

  7. Chest tube drainage amount

    Time frame: From enrollment until day 3 of intervention

    Evaluate the difference in amount (mL) of pleural fluid drained between once daily and twice daily IET groups

  8. Duration of chest tube placement

    Time frame: 90 days

    Evaluate the number of days of chest tube placement between once daily and twice daily IET groups

  9. Difference in pleural opacification on chest x-ray imaging between once daily IET and twice daily IET

    Time frame: From enrollment to 48 hours after completing 3 days of intrapleural enzyme therapy

    Measure the difference of pleural opacification on chest x-ray imaging, as measured in centimeter cubed (cm^3), between once daily IET compared to twice daily IET

  10. Percent of participants who have pleural hemorrhage requiring blood transfusion

    Time frame: From enrollment to 48 hours after completing 3 days of intrapleural enzyme therapy

    Measure the percent of participants who have pleural hemorrhage requiring blood transfusion

Sponsors and collaborators

Lead sponsor

University of North Carolina, Chapel Hill

Other

Collaborators

  • Dartmouth-Hitchcock Medical Center
  • Henry Ford Health System
  • Northwestern Memorial Hospital
  • Rush University Medical Center
  • Yale University

Registry information

Official study title

Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema (ONLY ONCE)

Acronym: ONLY ONCE

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Jul 31, 2025
Registry last updated
May 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.