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

The Hospital for Sick Children97 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Pleural Empyema

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (6)

Alberta Children's Hospital

Calgary, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

McMaster Children's Hospital

Hamilton, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

The Hospital for Sick Children(SickKids)

Toronto, Ontario, Canada

CHU Sainte Justine

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

Time to Hospital Discharge

Time from insertion of the chest drain to discharge from hospital.

Time frame: up to 4 months

Secondary Outcomes

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

Time frame: up to 4 months

Time to Drain Removal

Time from drain insertion to drain removal.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: up to 4 months

Mortality

Mortality from any cause during the hospitalization for empyema.

Time frame: up to 4 months