Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)
Condition: Pleural Empyema
MeSH terms: Empyema; Empyema, Pleural
Intervention: TPA (Tissue Plasminogen Activator); DNase; Placebo
Intervention description: Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days; Intrapleural administration of DNase 5 mg diluted to 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days; Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg)
Intervention MeSH terms: Tissue Plasminogen Activator; Plasminogen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 97.0
Sex: All
Minimum age: 6 Months
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Randomized controlled trial; Pleural Empyema; tPA; DNase

Summary:

      Bacterial pneumonia can be complicated by the development of excess fluid and pus (pleural
      empyema) around the lungs in children. The incidence of pleural empyema in children has
      increased significantly in the last 10 years.

      Short term morbidity for this condition is substantial, but unlike in adults, the long term
      outcome of this condition for children in developed countries is favourable. Inserting a
      chest drain and then adding a medicine (tissue plasminogen activator - tPA) to break down
      organized pus has been shown to be an effective therapy for reducing the duration of illness.
      However, this treatment is still suboptimal and prolonged hospitalization is common. Recent
      data from adults suggests that adding an additional medicine (DNase) to decrease the
      viscosity (thickness) of the fluid improves drainage and leads to better patient outcomes;
      however, there are no published studies on children.

      This is a multi-centre randomized controlled trial comparing the time to discharge from
      hospital after chest drain insertion in previously well children who present with pleural
      empyema, treated with intrapleural DNase and tissue plasminogen activator (tPA) by chest
      drain for three doses over 48 hours compared with three doses over 48 hours of tPA alone.
      Other outcomes related to effectiveness, safety and cost will be assessed as well.
    

Eligibility criteria:

        Inclusion Criteria:

          1. age 6 months to 18 years

          2. hospitalized with diagnosis of pleural empyema requiring chest tube drainage with
             fibrinolytics as judged by the attending physician with the following criteria:

               1. pneumonia with pleural effusion as documented on ultrasound of the chest; AND

               2. need for further intervention in addition to antibiotics based on clinical
                  criteria [persistent fever despite on antibiotics for at least 48 hours OR
                  significant respiratory distress tachypnea, hypoxia) as a result of the pleural
                  fluid collection]

        Exclusion Criteria:

          1. empyema as a result of tuberculosis, fungus or non-infectious causes (e.g. malignancy)

          2. known coagulation impairment

          3. suspected or proven allergy to tPA or DNase

          4. chronic lung disease or other chronic illnesses (e.g. immunodeficiency or neurologic
             impairment)

          5. child has already undergone a drainage procedure (e.g. chest drain or VATS).

          6. recent administration of an investigational drug (within previous 30 days)

          7. pregnancy

          8. breastfeeding