Intrapleural Enzyme Therapy for Pleural Infection

(ONLY ONCE Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Pregnancy, Prisoners, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering medications once a day is as effective as twice a day for treating pleural infections, which occur around the lungs. The treatments, tPA and DNase (intrapleural enzyme therapy), are delivered through a chest tube to help clear the infection. Researchers aim to determine differences in patient outcomes and the amount of fluid remaining in the chest between the two dosing schedules. This trial suits individuals hospitalized with a lung infection who are already receiving care, including a chest tube. Participants will be randomly assigned to receive the medication either once or twice daily. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on blood thinners or antiplatelet drugs, you may need to stop them for 48 hours before starting the trial treatment.

What is the safety track record for intrapleural enzyme therapy?

Research has shown that intrapleural enzyme therapy, which involves placing medications like tPA and DNase into the chest to treat infections around the lungs, is generally safe. Studies indicate a high success rate for this treatment, with about 90% to 94% of cases seeing improvement, effectively clearing the infection in most instances.

The risk of bleeding with this therapy is low, but caution is advised if the patient is also taking blood thinners, as this can increase the risk. One study found that this therapy can reduce the need for surgery and shorten hospital stays, suggesting it is well-tolerated by patients.

Overall, previous studies have shown positive results, making it a promising option for those dealing with infections around the lungs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about intrapleural enzyme therapy for pleural infection because it offers a new way to help the body break down and clear infection in the pleural space, which is the area between the lungs and the chest wall. Traditional treatments for pleural infections often involve antibiotics and sometimes surgery, but this therapy uses enzymes delivered directly into the pleural space to enhance the body's natural ability to resolve infections. A key feature of this treatment is its potential to work faster than typical methods, as it can show results in just a few days rather than weeks. Additionally, the trial is exploring different dosing schedules, with some participants receiving the therapy once daily and others twice daily, which could provide insights into optimizing treatment efficacy and convenience.

What evidence suggests that intrapleural enzyme therapy could be effective for pleural infection?

Research has shown that intrapleural enzyme therapy, which uses special proteins called tPA and DNase, effectively treats infections in the space around the lungs. Studies have found that this treatment helps clear fluid from around the lungs, improving drainage and reducing the need for surgery. Intrapleural enzyme therapy has succeeded in up to 94% of past patients, shortening hospital stays and speeding up recovery. This trial will compare different dosing schedules of intrapleural enzyme therapy, with one group receiving the therapy twice daily and another group receiving it once daily. ^{1 5 6 7 8}

Who Is on the Research Team?

Jason Akulian, MD, MPH

Principal Investigator

University of North Carollina at Chapel Hill

Are You a Good Fit for This Trial?

Adults hospitalized with lung infections, who have a chest tube in place and meet specific lab criteria (like pH < 7.2 or glucose < 60mg/dL in pleural fluid), can join this trial. They must be able to follow the study procedures and not have a life expectancy under 3 months due to other conditions, known allergies to the medications used, recent major health events like stroke or surgery, or be on certain blood thinners.

Inclusion Criteria

Pleural fluid that is macroscopically purulent or pleural fluid gram stain or culture positive for bacteria, potential of hydrogen (pH) < 7.2, Pleural fluid glucose < 60mg/dL, Pleural fluid Lactate Dehydrogenase (LDH) > 1,000 IU/L

I am in the hospital for fluid in my chest that was drained with a tube.

Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee

Exclusion Criteria

I have a life expectancy of less than 3 months due to a condition unrelated to my pleural infection.

Known pregnancy or lactating females

Prisoners

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intrapleural enzyme therapy (IET) once or twice daily for 3 consecutive days

3 days

Daily hospital visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of mortality, hospitalization length, and other health metrics

90 days

Extended Follow-up

Participants are monitored for long-term outcomes such as surgery and/or mortality

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Intrapleural Enzyme Therapy

Trial Overview The trial is testing if administering enzymes (tPA and DNase) once daily into the space around the lungs is as effective as giving them twice daily for clearing infections. It's random whether participants get one dose or two per day, aiming to compare outcomes like remaining fluid volume.

How Is the Trial Designed?

Group I: Once daily intrapleural enzyme therapy Experimental Treatment 2 Interventions

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

Group II: Twice daily intrapleural enzyme therapy Active Control 2 Interventions

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

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11916173/

Perspective and update: intrapleural fibrinolytic therapy for ... The successful MIST2 trial demonstrated that IPFT improves pleural opacification, reduces hospital stays, and decreases short-term surgical ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1012740

Intrapleural Use of Tissue Plasminogen Activator and ... Intrapleural t-PA–DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10749719/

A Retrospective Cohort Study Evaluating the Safety and ... This translates to a treatment success rate of 90.5% and 94.1% for sequential and concurrent intrapleural therapy, respectively. There was no ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07095361

Once Daily Intrapleural Enzyme Therapy in Complicated ... Expected survival of less than 3 months due to a pathologic condition other than that causing the pleural infection. Ages Eligible for Study. 18 Years and older ...

5. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02949-1

Surgery versus intrapleural fibrinolysis for management of ... Results. Surgical management of complicated pleural infections was more likely to be successful than intrapleural fibrinolysis (RR 1.18; 95% CI ...

6. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/s12931-025-03184-y

Perspective and update: intrapleural fibrinolytic therapy for ... The successful MIST2 trial demonstrated that IPFT improves pleural opacification, reduces hospital stays, and decreases short-term surgical ...

7. journal.chestnet.org journal.chestnet.org/article/S0012-3692(23)03365-2/fulltext

A RETROSPECTIVE REVIEW - CHEST Journal Treatment success was 93.3%. Treatment failure, defined by in-hospital mortality attributed to pleural infection, or the need for surgical ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0012369222010893

Bleeding Risk With Combination Intrapleural Fibrinolytic ... IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation.