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 complex 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: We will conduct a prospective randomized clinical trial. We plan to enroll a total of 80 patients and randomize them 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 Primary Outcome: Duration of hospital stay after intervention Secondary Outcome: Failure rate of assigned treatment and adverse events Potential Outcome and Benefit: Determine best strategy for treating patients with pleural infection

Official Title
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Fibrinolytic Therapy Versus Medical Thoracoscopy for Treatment of Pleural Infection: A Randomized Clinical Trial

Conditions
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Pleural Infection, Pleural Diseases

Intervention / Treatment
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* Other: Medical Thoracoscopy
* Other: Fibrinolytic Group


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: Thoracoscopy group<br>Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. | Other: Medical Thoracoscopy<br>* Medical thoracoscopy will be performed as per standard protocols.<br>|
| Active Comparator: Fibrinolytic group<br>Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) | Other: Fibrinolytic Group<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 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hospital stay after intervention | Number of days hospitalized | 12 week follow up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days with chest drainage | Number of days with chest drainage | 12 week follow up period | 
| Total length of hospital stay | Total days spent in the hospital | 12 week follow up period | 
| Failure rate of assigned treatment necessitating intervention | defined as any of the following: Surgical intervention (VATS, open thoracotomy) in the medical thoracoscopy or fibrinolytic therapy arm Need of additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to clinical non-responsiveness Need of additional chest tube in the fibrinolytic therapy arm due to clinical non-responsiveness | 12 week follow up period | 
| Adverse events | Any adverse event (pain or 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 | 
| Change in pleural fluid volume on Chest CT scan prior to randomization (day 0) to prior to chest tube removal measured by radiologist blinded to treatment allocation using image J software | Pleural fluid volume measured with CT scan | 12 week follow up period | 
| Inflammatory biomarker (CRP) from randomization (day 0), at 6 weeks and 12 weeks respectively | Inflammatory biomarker measure | at randomization and at 6 and12 week follow up visit | 
| Total costs of each treatment modality | Total cost of each of treatment modality | 6 and 12 week follow up period |