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Completed

NCT Number: NCT01717742

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

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.

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Key information

Conditions

Pleural Empyema Empyema Empyema, Pleural Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Pleural Diseases Respiratory Tract Diseases Respiratory Tract Infections Suppuration

Age range

6 month–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Alberta Children's Hospital, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TPA (Tissue Plasminogen Activator)

Drug

Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days

Other names: Cathflo (alteplase, recombinant)

DNase

Drug

Intrapleural administration of DNase 5 mg diluted to 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days

Other names: Pulmozyme (Dornase alfa)

Placebo

Other

Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg)

Other names: Normal saline

Primary outcomes

  1. Time to Hospital Discharge

    Time frame: up to 4 months

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

Secondary outcomes

  1. Time to Meeting Discharge Criteria

    Time frame: up to 4 months

    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

  2. Time to Drain Removal

    Time frame: up to 4 months

    Time from drain insertion to drain removal.

  3. Duration of Fever After Intervention

    Time frame: up to 4 months

    Duration of fever (defined as temperature >38 degrees celsius taken by any method) from insertion of the chest drain until resolution.

  4. Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention

    Time frame: up to 4 months

    Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.

  5. Number of Participants With Serious Bleeding

    Time frame: up to 4 months

    Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.

  6. Number of Participants With Further Interventions

    Time frame: up to 4 months

    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.

  7. Number of Participants With Hospital Readmission

    Time frame: 3 months post-discharge

    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.

  8. Cost of the Hospitalization

    Time frame: up to 4 months

    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.

  9. Mortality

    Time frame: up to 4 months

    Mortality from any cause during the hospitalization for empyema.

Other outcomes

  1. Chest Radiography

    Time frame: 7 days after drain removal

    The radiograph closest to the time of drain removal will be reviewed by a blinded study radiologist to determine the percentage of hemithorax occupied using a 5 point ordinal scale utilized in previous studies ranging from no fluid present to fluid occupying >75% of the most affected hemithorax.

Sponsors and collaborators

Lead sponsor

The Hospital for Sick Children

Other

Collaborators

  • British Columbia Children's Hospital
  • Canadian Institutes of Health Research (CIHR)
  • Children's Hospital of Eastern Ontario
  • McMaster Children's Hospital
  • St. Justine's Hospital
  • The Physicians' Services Incorporated Foundation
  • Unity Health Toronto

Registry information

Important dates

Study start
2012
Primary completion
2017
Study completion
2017
First posted
Oct 30, 2012
Registry last updated
Apr 14, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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