Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)

The Hospital for Sick Children

Status and phase: Completed; Phase 3

Conditions: Pleural Empyema

Treatments: Drug: DNase; Other: Placebo; Drug: TPA (Tissue Plasminogen Activator)

Study type: Interventional

Funder types: Other

Identifiers

NCT01717742

1000033767

Details and patient eligibility

About

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.

Enrollment: 97 patients

Sex: All

Ages: 6 months to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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97 participants in 2 patient groups

tPA and placebo

Active Comparator group

Treatment:

Other: Placebo

Drug: TPA (Tissue Plasminogen Activator)

tPA and DNase

Experimental group

Treatment:

Drug: DNase

Drug: TPA (Tissue Plasminogen Activator)