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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pleural Empyema

Intervention / Treatment
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* Drug: TPA (Tissue Plasminogen Activator)
* Drug: DNase
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 6 months to 18 years hospitalized with diagnosis of pleural empyema requiring chest tube drainage with fibrinolytics as judged by the attending physician with the following criteria: pneumonia with pleural effusion as documented on ultrasound of the chest; AND 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: empyema as a result of tuberculosis, fungus or non-infectious causes (e.g. malignancy) known coagulation impairment suspected or proven allergy to tPA or DNase chronic lung disease or other chronic illnesses (e.g. immunodeficiency or neurologic impairment) child has already undergone a drainage procedure (e.g. chest drain or VATS). recent administration of an investigational drug (within previous 30 days) pregnancy breastfeeding

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tPA and placebo<br> | Drug: TPA (Tissue Plasminogen Activator)<br>* Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days<br>* Other names: Cathflo (alteplase, recombinant);Other: Placebo<br>* Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg)<br>* Other names: Normal saline;|
| Experimental: tPA and DNase<br> | Drug: TPA (Tissue Plasminogen Activator)<br>* Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days<br>* Other names: Cathflo (alteplase, recombinant);Drug: DNase<br>* Intrapleural administration of DNase 5 mg diluted to 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days<br>* Other names: Pulmozyme (Dornase alfa);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Hospital Discharge | Time from insertion of the chest drain to discharge from hospital. | up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Meeting Discharge Criteria | Time from insertion of the chest drain to meeting discharge criteria. Discharge criteria: Chest tube removed No fever [temperature less than 38°C] Normal respiratory rate forage No hypoxia Drinking fluids wel | up to 4 months | 
| Time to Drain Removal | Time from drain insertion to drain removal. | up to 4 months | 
| Duration of Fever After Intervention | Duration of fever (defined as temperature >38 degrees celsius taken by any method) from insertion of the chest drain until resolution. | up to 4 months | 
| Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention | Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention. | up to 4 months | 
| Number of Participants With Serious Bleeding | Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion. | up to 4 months | 
| Number of Participants With Further Interventions | Number of participants who needed further intervention such as placement of another chest drain (by any technique) or surgical intervention such as thoracotomy and decortication, video-assisted thorascopic surgery, or pneumonectomy. | up to 4 months | 
| Number of Participants With Hospital Readmission | Number of Participants who had any hospital readmission after discharge from hospital for initial treatment for pleural empyema within three months related to pleural empyema or its treatment. | 3 months post-discharge | 
| Cost of the Hospitalization | An economic evaluation will compare the relative costs of DNase-tPA with tPA alone in previously well children who present with pleural empyema, using patient-level data from the trial. | up to 4 months | 
| Mortality | Mortality from any cause during the hospitalization for empyema. | up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tPA, Randomized controlled trial, Pleural Empyema, DNase