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

NCT01717742 | Completed Phase 3 Results DMC

• 1 other identifier: 1000033767
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 6

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.

Conditions

Pleural Empyema

Keywords

Randomized controlled trial; Pleural Empyema; tPA; DNase

Outcome Measures

Primary Outcomes (1)

• Time to Hospital Discharge

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

  up to 4 months

Secondary Outcomes (9)

• Time to Meeting Discharge Criteria

  up to 4 months

• Time to Drain Removal

  up to 4 months

• Duration of Fever After Intervention

  up to 4 months

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

  up to 4 months

• Number of Participants With Serious Bleeding

  up to 4 months

Other Outcomes (1)

• Chest Radiography

  7 days after drain removal

Study Arms (2)

tPA and placebo

ACTIVE COMPARATOR

Drug: TPA (Tissue Plasminogen Activator); Other: Placebo

tPA and DNase

EXPERIMENTAL

Drug: TPA (Tissue Plasminogen Activator); Drug: DNase

Interventions

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

Also known as: Cathflo (alteplase, recombinant)

tPA and DNase; tPA and placebo

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

Also known as: Pulmozyme (Dornase alfa)

tPA and DNase

Placebo OTHER

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

Also known as: Normal saline

tPA and placebo

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 \[persistent fever despite on antibiotics for at least 48 hours OR significant respiratory distress tachypnea, hypoxia) as a result of the pleural fluid collection\]

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (6)

Alberta Children's Hospital

Calgary, Alberta, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, BC V6H 3N1, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

The Hospital for Sick Children(SickKids)

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (2)

• 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.

  PMID: 32011642 RESULT

• 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.

  PMID: 28646887 DERIVED

MeSH Terms

Conditions

Empyema, Pleural

Interventions

Tissue Plasminogen Activator; Deoxyribonucleases; dornase alfa; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Esterases; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Eyal cohen
• Organization: Hospital for Sick Children

eyal.cohen@sickkids.ca

416-813-7654

Study Officials

• Eyal Cohen, MD, MSc

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 30, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 14, 2020
• Results First Posted: April 3, 2020

Record last verified: 2020-04

Locations

CA (6)