Fibrinolysis Compared to Thoracoscopy for Pleural Infection

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

• tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) (Drug): 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
• Medical Thoracoscopy (Procedure), also known as Pleuroscopy: Medical thoracoscopy will be performed as per standard protocols.

Primary outcomes

• Duration of Hospital Stay After Intervention [12 week follow up period]: duration of hospital stay in days from time of procedure to discharge from hospital.

Secondary outcomes

• Total Length of Hospital Stay [12 week follow up period]: Total days spent in the hospital
• Number of Participants Necessitating Intervention After the Assigned Treatment [12 week follow up period]: 1. Need for surgical intervention (VATS, Open Thoracotomy) in any arm 2. Need for additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to treatment failure 3. Need of additional chest tube or additional fibrinolytic doses in the fibrinolytic therapy arm due to treatment failure
• Adverse Events [12 week follow up period]: any Adverse events (pain, bleeding)
• In Hospital and 30-day Mortality [30 days]: Death of a patient while being hospitalized or up to 30 days after

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Duration of Hospital Stay After Intervention (Primary), Median, days: Fibrinolytic Therapy Group 4 (4 to 5.5); Medical Thoracoscopy Group 2 (2 to 5)
• Total Length of Hospital Stay (Secondary), Median, days: Fibrinolytic Therapy Group 6 (5 to 8.5); Medical Thoracoscopy Group 3.5 (2 to 10)
• Number of Participants Necessitating Intervention After the Assigned Treatment (Secondary), Count of participants, Participants: Fibrinolytic Therapy Group 3; Medical Thoracoscopy Group 4
• Adverse Events (Secondary), Count of participants, Participants: Fibrinolytic Therapy Group 1; Medical Thoracoscopy Group 1
• In Hospital and 30-day Mortality (Secondary), Count of participants, Participants: Fibrinolytic Therapy Group 0; Medical Thoracoscopy Group 1

Adverse events

Time frame: The perioperative period until hospital discharge, an average of 4 weeks per participant

Other adverse events by term

• Study Protocol (PDF, 2017-07-01)
• Statistical Analysis Plan (PDF, 2017-07-01)

• Fayez Kheir, MD, MSc, Principal investigator, Tulane University