Fibrinolysis Compared to Thoracoscopy for Pleural Infection

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

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.

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

Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase)

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

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

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

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

Kheir F, Thakore S, Mehta H, Jantz M, Parikh M, Chee A, Kaphle U, Sisnega C, Fernandez-Bussy S, Majid A. Intrapleural Fibrinolytic Therapy versus Early Medical Thoracoscopy for Treatment of Pleural Infection. Randomized Controlled Clinical Trial. Ann Am Thorac Soc. 2020 Aug;17(8):958-964. doi: 10.1513/AnnalsATS.202001-076OC.