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

Pleural Empyema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01717742
• Other study ID #: 1000033767
• Status: Completed
• Phase: Phase 3
• Start date: December 2012
• Est. completion date: December 2017

Study information

• Verified date: April 2020
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Empyema
• Empyema, Pleural
• Pleural Empyema

Intervention

Drug:
• TPA (Tissue Plasminogen Activator)
Intrapleural administration of tPA 4 mg in 10 ml (=10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days
• 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:
• Placebo
Intrapleural administration of normal saline 10 ml (=10 kg) or 20 ml (>10 kg)

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	McMaster Children's Hospital	Hamilton	Ontario
Canada	CHU Sainte Justine	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	The Hospital for Sick Children(SickKids)	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia

Sponsors (8)

Lead Sponsor	Collaborator
The Hospital for Sick Children	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, St. Michael's Hospital, Toronto, The Physicians' Services Incorporated Foundation

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Livingston MH, Mahant S, Connolly B, MacLusky I, Laberge S, Giglia L, Yang C, Roberts A, Shawyer A, Brindle M, Parsons S, Stoian C, Walton JM, Thorpe KE, Chen Y, Zuo F, Mamdani M, Chan C, Loong D, Isaranuwatchai W, Ratjen F, Cohen E. Effectiveness of Intr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Chest Radiography	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.	7 days after drain removal
Primary	Time to Hospital Discharge	Time from insertion of the chest drain to discharge from hospital.	up to 4 months
Secondary	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
Secondary	Time to Drain Removal	Time from drain insertion to drain removal.	up to 4 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality	Mortality from any cause during the hospitalization for empyema.	up to 4 months