Pleural Infection BacterialPhase 4ONLY ONCENCT07095361
Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema
A Phase 4 study testing Fibrinolytic once daily, Fibrinolytic twice daily and DNA degradation once daily in people with Pleural Infection Bacterial and Pleural Infections, run by University of North Carolina, Chapel Hill at 11 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Infection Bacterial, Pleural Infections, Pleural Infections and Inflammations
- What is being tested?
- Fibrinolytic once daily, Fibrinolytic twice daily and DNA degradation once daily
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 11 sitesUnited States
- Study dates
- 11 Sep 2025to 30 Sep 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 11 recruiting
- Recruiting
UNC Chapel Hill
Chapel Hill, North Carolina, 27514
Hee Jae Choi, DO, 919-966-2533, heejae.choi@unchealth.unc.edu
Ashley Delgado, BS, 919-445-0367, ashley_delgado@med.unc.edu
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Christopher Kapp, MD, (312) 695-3800, christopher.kapp@nm.org
Study Coordinator, adriana.martinez@northwestern.edu
- Recruiting
Rush University Medical Center
Chicago, Illinois, 60612
James Katsis, MD, (312) 942-6744, James_Katsis@rush.edu
Study Coordinator, Kimberly_P_Saulsberry@rush.edu
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Labib G Debiane, MD, (866) 434-0076, ldebian1@hfhs.org
Study Coordinator, rgeorg11@HFHS.ORG
- Recruiting
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03766
John Howe, MD, 603-650-5533, John.E.Howe@hitchcock.org
Study Coordinator, Bailey.D.Starr@hitchcock.org
- Recruiting
University of Arkansas Medical Center
Little Rock, Arkansas, 72205
Nikhil Meena, MD, 501-296-1200, nkmeena@uams.edu
Monica Smith, 501-686-8539, MRSmith@uams.edu
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Samira Shojaee, MD, (615) 322-2386, samira.shojaee@vumc.org
Hee Jae Choi, DO, 408-324-4644, heejae.choi@vumc.org
- Recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06510
Erin DeBiasi, MD, (203) 785-4198, erin.debiasi@yale.edu
Study Coordinator, zubaida.dabre@yale.edu
- Recruiting
NYU Langone Health
New York, New York, 10016
Andrew DeMaio, MD, 212-731-5637, andrew.demaio@nyulangone.org
Rosemary Schluger, 212-263-0255, Rosemary.Schluger@nyulangone.org
- Recruiting
Stanford Hospital
Palo Alto, California, 94305
Brian Shaller, MD, (650) 725-5071, bshaller@stanford.edu
Michelle Imperio, MD, 650-736-0125, imperio@stanford.edu
- Recruiting
UCSD Hillcrest Medical Center
San Diego, California, 92103
Bryce Duchman, MD, (800) 926-8273, brduchman@health.ucsd.edu
Sonia Sekhon, (619) 543-5864, sosekhon@health.ucsd.edu
About this study
Official title: Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema (ONLY ONCE)
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:
Read more
- 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
- Being tested
- Fibrinolytic once daily, Fibrinolytic twice daily, DNA degradation once daily, DNA degradation twice daily
- Keywords
- Lytics, Intrapleural enzyme therapy, Once daily, lytic therapy
- Medical subject headings
- Inflammation, Empyema, Pleural, Empyema, Pleural Effusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrinolytic once dailyDrug
Also called once daily lytics, tPA once daily
tissue plasminogen activator (tPA) 10mg will be administered once a day as part of intrapleural enzyme therapy (IET) for 3 consecutive days.
Fibrinolytic twice dailyDrug
Also called lytics twice daily, tPA twice daily
tissue plasminogen activator (tPA) 10mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days.
DNA degradation once dailyDrug
Also called DNase once daily, lytics once daily
Deoxyribonuclease (DNase) 5mg will be administered once a day as intrapleural enzyme therapy (IET) for 3 consecutive days.
DNA degradation twice dailyDrug
Also called lytics twice daily, DNase twice daily
Deoxyribonuclease (DNase) 5mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Once daily intrapleural enzyme therapy | Experimental | Participants will receive intrapleural enzyme therapy (IET) once daily for 3 consecutive days. Receives: 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. Receives: Drug: Fibrinolytic twice daily; Drug: DNA degradation twice daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Secondary outcomes (10)
30 Day Mortality
Evaluate rate of mortality at 30 days between the participants receiving once daily IET and twice daily IET
Measured: 30 days
Hospital length of stay
Evaluate length of hospitalization stay between the participants receiving once daily IET and twice daily IET
Measured: 90 days
Oral Morphine Equivalents (OME)
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.
Measured: From enrollment until day 3 of intervention
Change of White Blood Cell Count
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.
Measured: From enrollment until day 3 of intervention
Change in C-reactive Protein (CRP) level
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.
Measured: From enrollment until day 3 of intervention
Change in Fever
Evaluate the difference between fever (in Celsius) between once daily IET and twice daily IET
Measured: From enrollment until day 3 of intervention
Chest tube drainage amount
Evaluate the difference in amount (mL) of pleural fluid drained between once daily and twice daily IET groups
Measured: From enrollment until day 3 of intervention
Duration of chest tube placement
Evaluate the number of days of chest tube placement between once daily and twice daily IET groups
Measured: 90 days
Difference in pleural opacification on chest x-ray imaging between once daily IET and twice daily IET
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
Measured: From enrollment to 48 hours after completing 3 days of intrapleural enzyme therapy
Percent of participants who have pleural hemorrhage requiring blood transfusion
Measure the percent of participants who have pleural hemorrhage requiring blood transfusion
Measured: From enrollment to 48 hours after completing 3 days of intrapleural enzyme therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start11 Sep 2025
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pleural Infection BacterialStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern Memorial Hospital, Henry Ford Health System, Yale University, Rush University Medical Center, Dartmouth-Hitchcock Medical Center
- Responsible party
- Sponsor
- Investigators
- Jason Akulian, MD, MPH, Principal investigator, University of North Carollina at Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07095361
- Sponsor's protocol ID
- 24-1309
- Acronym
- ONLY ONCE
- Status last verified
- Apr 2026
- First submitted
- 11 Jul 2025
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema (ONLY ONCE)
- ClinicalTrials.gov ID
- NCT07095361
- Acronym / sponsor ID
- ONLY ONCE / 24-1309
- Conditions
- Pleural Infection Bacterial, Pleural Infections, Pleural Infections and Inflammations, Empyema, Pleural, Empyema, Complicated Pleural Effusion/ Empyema
- Keywords
- Lytics, Intrapleural enzyme therapy, Once daily, lytic therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Northwestern Memorial Hospital, Henry Ford Health System, Yale University, Rush University Medical Center, Dartmouth-Hitchcock Medical Center
- Study start
- 11 Sep 2025 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 31 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Once daily intrapleural enzyme therapy | Experimental | Drug: Fibrinolytic once daily, Drug: DNA degradation once dailyParticipants will receive intrapleural enzyme therapy (IET) once daily for 3 consecutive days. |
| Twice daily intrapleural enzyme therapy | Active comparator | Drug: Fibrinolytic twice daily, Drug: DNA degradation twice dailyParticipants will receive intrapleural enzyme therapy (IET) twice daily for 3 consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fibrinolytic once dailyAlso: once daily lytics, tPA once dailytissue plasminogen activator (tPA) 10mg will be administered once a day as part of intrapleural enzyme therapy (IET) for 3 consecutive days. | Drug | Once daily intrapleural enzyme therapy |
| Fibrinolytic twice dailyAlso: lytics twice daily, tPA twice dailytissue plasminogen activator (tPA) 10mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days. | Drug | Twice daily intrapleural enzyme therapy |
| DNA degradation once dailyAlso: DNase once daily, lytics once dailyDeoxyribonuclease (DNase) 5mg will be administered once a day as intrapleural enzyme therapy (IET) for 3 consecutive days. | Drug | Once daily intrapleural enzyme therapy |
| DNA degradation twice dailyAlso: lytics twice daily, DNase twice dailyDeoxyribonuclease (DNase) 5mg will be administered twice a day as intrapleural enzyme therapy for 3 consecutive days. | Drug | Twice daily intrapleural enzyme therapy |
Primary outcome
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.
10 secondary outcomes
30 Day Mortality
Time frame: 30 days
Hospital length of stay
Time frame: 90 days
Oral Morphine Equivalents (OME)
Time frame: From enrollment until day 3 of intervention
Change of White Blood Cell Count
Time frame: From enrollment until day 3 of intervention
Change in C-reactive Protein (CRP) level
Time frame: From enrollment until day 3 of intervention
Change in Fever
Time frame: From enrollment until day 3 of intervention
Chest tube drainage amount
Time frame: From enrollment until day 3 of intervention
Duration of chest tube placement
Time frame: 90 days
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Individual participant dataSharing planned: Yes. Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jason Akulian, MD, MPH principal investigator
University of North Carollina at Chapel Hill
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fibrinolytic once daily, Fibrinolytic twice daily and DNA degradation once daily in people with Pleural Infection Bacterial and Pleural Infections, run by University of North Carolina, Chapel Hill at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IET Failure: Surgery and/or mortality at 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.