Fibrinolytic Therapy Versus Medical Thoracoscopy
Condition: Pleural Diseases
MeSH terms: Pleural Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      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 complicated pleural infections in adults as
      defined as complicated parapneumonic effusions or pleural empyema.
    

Detailed description: 
      Pleural infection (empyema or complex parapneumonic effusion [CPPE]) represents one of the
      common clinical diagnoses encountered in clinical practice in the United States (US) and
      worldwide. The incidence of pleural infection continues to rise with an annual incidence of
      approximately 65,000 in the US and United Kingdom (UK). It is associated with substantial
      morbidity and mortality as well as increased hospital costs despite advances in medical
      diagnostic and therapeutic strategies. The overall mortality of pleural infection approaches
      20% and it is above 30% in elderly patients over 65 years and immunocompromised patients.

      Treatment of CPPE or empyema requires antibiotics and drainage of the pleural cavity.3
      However, in about 30% of cases, it is difficult to remove the fluid due to loculations,
      septations and increased viscosity of the pleural fluid, and around 20% will need surgical
      intervention to adequately treat the pleural infection.

      Specific Aim 1:

      To compare the efficacy of early medical thoracoscopy versus fibrinolytic therapy (tPA/DNase)
      in patients with complicated parapneumonic effusions or pleural empyema.

      CPPE is defined as non-purulent effusion in a patient with clinical evidence of infection
      such as fever and/or elevated blood leukocyte count and/or elevated CRP, with pleural fluid
      pH ≤ 7.2 (measured by blood-gas analyzer), or pleural fluid glucose < 60 mg/dl or pleural
      fluid LDH >1000 IU/L26. Empyema is defined as pus within the pleural space and/or presence of
      bacteria on pleural fluid Gram stain or culture.

      For patients to be considered for the trial they need to fulfill one of the following
      criteria: 1) CPPE along with evidence of septated pleural effusion on pleural ultrasonography
      and/or chest CT scan or 2) empyema.
    

Intervention name(s): Chest thoracoscopy; Chest fibrinolytic therapy; tPA; DNase
Intervention type(s): Procedure; Procedure; Drug; Drug
Intervention description(s): Thoracoscopy will be performed as per standard protocols, with patient lateral decubitus position. Ten mLs of fluid will be collected to check for biomarkers. Adhesiolysis will be attempted and pleural irrigation will be done. At the end of the procedure, a drain will be inserted and connected to an underwater seal with a negative pressure suction; A chest tube will be inserted under ultrasonography into the most dependent area of the pleural effusion or into the largest loculation in patients with multi-loculated effusions. A of DNase and tPA will be given. Concurrent tPA and DNase will be administered intrapleurally through the chest tube followed by saline flush. The tube will then be clamped for 120 minutes and after which it will be connected back to wall suction. The intrapleural therapy will be given twice daily for a maximum of 6 doses.; tPA administered intrapleurally through the chest tube followed by saline flush. The intrapleural therapy will be given twice daily for a maximum of 6 doses.; DNase administered intrapleurally through the chest tube followed by saline flush. The intrapleural therapy will be given twice daily for a maximum of 6 doses.
Other intervention name(s): Actilyse; pulmozyme
Intervention MeSH terms: Tissue Plasminogen Activator
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomly assigned to receive one of two standard-of-care treatments for severe pleural infection.
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment