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

This study is currently recruiting participants.
Verified January 2013 by The Hospital for Sick Children
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Children's Hospital of Eastern Ontario
Hospital St. Justine
St. Michael's Hospital, Toronto
The Physicians' Services Incorporated Foundation
Information provided by (Responsible Party):
Eyal Cohen, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT01717742
First received: October 25, 2012
Last updated: January 7, 2013
Last verified: January 2013
History of Changes
  Purpose

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 Intervention Phase
Pleural Empyema
 Drug: tPA
Drug: DNase
Other: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Time to hospital discharge [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    Time from insertion of the chest drain to discharge from hospital.


Secondary Outcome Measures:
  • Time to meeting discharge criteria [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    Time from insertion of the chest drain to meeting discharge criteria.

  • Time to drain removal [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    Time from drain insertion to drain removal.

  • Duration of fever after intervention [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    Duration of fever (defined as temperature >38 degrees celsius taken by any method) from insertion of the chest drain until resolution.

  • Need for ventilatory support or non-invasive ventilation following the intervention [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    Need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.

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

  • Need for further interventions [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    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.

  • Hospital readmission [ Time Frame: 3 months post-discharge ] [ Designated as safety issue: No ]
    Any hospital readmission after discharge from hospital for initial treatment for pleural empyema within three months related to pleural empyema or its treatment.

  • Cost of the hospitalization [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    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.

  • Mortality [ Time Frame: up to 4 months ] [ Designated as safety issue: Yes ]
    Mortality from any cause during the hospitalization for empyema.


Other Outcome Measures:
  • Chest radiography [ Time Frame: 7 days after drain removal ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 98
Study Start Date: December 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01717742

Contacts
Contact: Eyal cohen, MD, MSc 416-813-5795 eyal.cohen@sickkids.ca
Contact: Sanjay Mahant, MD, MSc 416-813-8422 sanjay.mahant@sickkids.ca

Locations
Canada, Ontario
Children's Hospital of Eastern Ontario Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Ian Maclusky, MD     613-737-7600        
Sub-Investigator: Ian Maclusky, MD            
The Hospital for Sick Children(SickKids) Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Eyal Cohen, MD, MSc     416-813-5795     eyal.cohen@sickkids.ca    
Contact: Sanjay Mahant, MD, MSc     416-813-8422     sanjay.mahant@sickkids.ca    
Principal Investigator: Eyal Cohen, MD, MSc            
Sub-Investigator: Sanjay Mahant, MD, MSc            
Sub-Investigator: Felix Ratjen, MD            
Sub-Investigator: Bairbre Connolly, MD            
Canada, Quebec
CHU Sainte Justine Not yet recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Sophie Laberge, MD     514-345-4931 ext 5409     sophie.laberge@umontreal.ca    
Sub-Investigator: Sophie Laberge, MD            
Sponsors and Collaborators
The Hospital for Sick Children
Canadian Institutes of Health Research (CIHR)
Children's Hospital of Eastern Ontario
Hospital St. Justine
St. Michael's Hospital, Toronto
The Physicians' Services Incorporated Foundation
Investigators
Principal Investigator: Eyal Cohen, MD, MSc The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Eyal Cohen, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01717742     History of Changes
Other Study ID Numbers: 1000033767
Study First Received: October 25, 2012
Last Updated: January 7, 2013
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by 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
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on May 23, 2013