Clinical trial NCT01717742: Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)
Official title: Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pleural Empyema
Keywords: Randomized controlled trial
Pleural Empyema
tPA
DNase
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Children's Hospital of Eastern Ontario
name: St. Justine's Hospital
name: Unity Health Toronto
name: The Physicians' Services Incorporated Foundation
name: McMaster Children's Hospital
name: British Columbia Children's Hospital
First posted: 2012-10-30
Enrollment: 97
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Time to Hospital Discharge
timeFrame: up to 4 months
Secondary outcomes:
measure: Time to Meeting Discharge Criteria
timeFrame: up to 4 months
measure: Time to Drain Removal
timeFrame: up to 4 months
measure: Duration of Fever After Intervention
timeFrame: up to 4 months
measure: Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention
timeFrame: up to 4 months
measure: Number of Participants With Serious Bleeding
timeFrame: up to 4 months
measure: Number of Participants With Further Interventions
timeFrame: up to 4 months
measure: Number of Participants With Hospital Readmission
timeFrame: 3 months post-discharge
measure: Cost of the Hospitalization
timeFrame: up to 4 months
measure: Mortality
timeFrame: up to 4 months
Other outcomes:
measure: Chest Radiography
timeFrame: 7 days after drain removal
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children(SickKids)
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte Justine
state: Quebec
Study officials:
affiliation: The Hospital for Sick Children
name: Eyal Cohen, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema: A Randomized Clinical Trial. JAMA Pediatr. 2020 Apr 1;174(4):332-340. doi: 10.1001/jamapediatrics.2019.5863.
citation: Livingston MH, Mahant S, Ratjen F, Connolly BL, Thorpe K, Mamdani M, Maclusky I, Laberge S, Giglia L, Walton JM, Yang CL, Roberts A, Shawyer AC, Brindle M, Parsons SJ, Stoian CA, Cohen E. Intrapleural Dornase and Tissue Plasminogen Activator in pediatric empyema (DTPA): a study protocol for a randomized controlled trial. Trials. 2017 Jun 24;18(1):293. doi: 10.1186/s13063-017-2026-0.