Fibrinolysis Compared to Thoracoscopy for Pleural Infection

Study Overview
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Brief Summary
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The purpose of this prospective randomized clinical trial is to compare two currently accepted standard-of-care treatment strategies: Medical thoracoscopy as compared to instillation of intrapleural tissue Plasminogen Activator (TPA) and human recombinant Deoxyribonuclease (DNase) for the management of empyema or complicated parapneumonic effusion (CPPE) in adults.

Detailed Description
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Background: Pleural infection (empyema or complex parapneumonic effusion (CPPE)) represents one of the most common clinical diagnoses encountered in clinical practice in the United States (US) It is associated with substantial morbidity and mortality despite advances in medical diagnostic and therapeutic strategies. Objective: Compare two standard of care treatments: TPA/DNase vs early medical Thoracoscopy Methods: Investigators will conduct a prospective randomized clinical trial. Plan is to enroll total of 32 patients and randomize those patients to either Medical Thoracoscopy group or Fibrinolytic Therapy group. Follow-up will be daily until hospital discharge and at 6 and 12 weeks in the outpatient setting Potential Outcome and Benefit: Determine best strategy for treating patients with pleural infection

Official Title
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Intrapleural Tissue Plasminogen Activator and Deoxyribonuclease Therapy Versus Early Medical Thoracoscopy for Treatment of Pleural Infection: A Randomized Clinical Trial

Conditions
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Pleural Infection, Empyema, Pleural Diseases, Parapneumonic Effusion

Intervention / Treatment
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* Drug: tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase)
* Procedure: Medical Thoracoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects >18 years old with: Evidence of empyema or complex parapneumonic effusion Exclusion Criteria: Age <18 years Pregnancy Inability to give informed written consent Previous thoracic surgery or thrombolytic therapy for pleural infection Medical thoracoscopy cannot be performed within 48 hours Hemodynamic instability or severe hypoxemia Non corrected coagulopathy Homogeneously echogenic effusion on pleural ultrasonography

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fibrinolytic therapy group<br>Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. | Drug: tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase)<br>* Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose<br>|
| Active Comparator: Medical Thoracoscopy group<br>Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. | Procedure: Medical Thoracoscopy<br>* Medical thoracoscopy will be performed as per standard protocols.<br>* Other names: Pleuroscopy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Hospital Stay After Intervention | duration of hospital stay in days from time of procedure to discharge from hospital. | 12 week follow up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Length of Hospital Stay | Total days spent in the hospital | 12 week follow up period | 
| Number of Participants Necessitating Intervention After the Assigned Treatment | Need for surgical intervention (VATS, Open Thoracotomy) in any arm Need for additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to treatment failure Need of additional chest tube or additional fibrinolytic doses in the fibrinolytic therapy arm due to treatment failure | 12 week follow up period | 
| Adverse Events | any Adverse events (pain, bleeding) | 12 week follow up period | 
| In Hospital and 30-day Mortality | Death of a patient while being hospitalized or up to 30 days after | 30 days |