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

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ClinicalTrials.gov Identifier: NCT01717742
Recruitment Status : Completed
First Posted : October 30, 2012
Last Update Posted : December 22, 2017
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Children's Hospital of Eastern Ontario
St. Justine's Hospital
St. Michael's Hospital, Toronto
The Physicians' Services Incorporated Foundation
McMaster Children's Hospital
British Columbia Children's Hospital
Information provided by (Responsible Party):
Eyal Cohen, The Hospital for Sick Children

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Pleural Empyema Drug: tPA Drug: DNase Other: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)
Study Start Date : December 2012
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Alteplase

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: tPA and placebo Drug: tPA
Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days
Other Name: Cathflo (alteplase, recombinant)

Other: Placebo
Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg)
Other Name: Normal saline
Experimental: tPA and DNase Drug: tPA
Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days
Other Name: Cathflo (alteplase, recombinant)

Drug: DNase
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 Name: Pulmozyme (Dornase alfa)


Outcome Measures
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Primary Outcome Measures :
  1. Time to hospital discharge [ Time Frame: up to 4 months ]
    Time from insertion of the chest drain to discharge from hospital.


Secondary Outcome Measures :
  1. Time to meeting discharge criteria [ Time Frame: up to 4 months ]
    Time from insertion of the chest drain to meeting discharge criteria.

  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. Need for ventilatory support or non-invasive ventilation following the intervention [ Time Frame: up to 4 months ]
    Need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.

  5. Serious bleeding [ Time Frame: up to 4 months ]
    Intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.

  6. Need for further interventions [ Time Frame: up to 4 months ]
    Need for 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. Hospital readmission [ Time Frame: 3 months post-discharge ]
    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 Outcome Measures:
  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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01717742


Locations
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, BC V6H 3N1
Canada, Ontario
McMaster Children's Hospital
Hamilton, Ontario, Canada, L8N 3Z5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
The Hospital for Sick Children(SickKids)
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
CHU Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
The Hospital for Sick Children
Canadian Institutes of Health Research (CIHR)
Children's Hospital of Eastern Ontario
St. Justine's Hospital
St. Michael's Hospital, Toronto
The Physicians' Services Incorporated Foundation
McMaster Children's Hospital
British Columbia Children's Hospital
Investigators
Principal Investigator: Eyal Cohen, MD, MSc The Hospital for Sick Children
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eyal Cohen, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01717742     History of Changes
Other Study ID Numbers: 1000033767
First Posted: October 30, 2012    Key Record Dates
Last Update Posted: December 22, 2017
Last Verified: December 2017

Keywords provided by Eyal Cohen, The Hospital for Sick Children:
Randomized controlled trial
Pleural Empyema
tPA
DNase

Additional relevant MeSH terms:
Empyema
Empyema, Pleural
Suppuration
Infection
Inflammation
Pathologic Processes
Respiratory Tract Infections
 Pleural Diseases
Respiratory Tract Diseases
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action