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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Children's Hospital of Eastern Ontario | OTHER |
| St. Justine's Hospital | OTHER |
| Unity Health Toronto |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tPA and placebo | Active Comparator |
| |
| tPA and DNase | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Hospital Discharge | Time from insertion of the chest drain to discharge from hospital. | up to 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Meeting Discharge Criteria | Time from insertion of the chest drain to meeting discharge criteria. Discharge criteria:
| up to 4 months |
| Time to Drain Removal |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eyal Cohen, MD, MSc | The Hospital for Sick Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alberta Children's Hospital | Calgary | Alberta | Canada | |||
| British Columbia Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32011642 | Result | 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. | |
| 28646887 |
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| ID | Title | Description |
|---|---|---|
| FG000 | tPA (Tissue Plasminogen Activator) and Placebo | tPA: Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days Placebo: Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg) |
| FG001 | tPA (Tissue Plasminogen Activator) and DNase | tPA: 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention (tPA & DNase) | Intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg |
| BG001 | Placebo (tPA & Placebo) | Intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Hospital Discharge | Time from insertion of the chest drain to discharge from hospital. | Posted | Mean | Standard Deviation | days | up to 4 months |
|
|
Over the course of the patient's hospitalization
All serious unexpected adverse events were reported to the REB. All serious adverse drug reactions to the study medication were reported to Health Canada within 15 calendar days or for death or life-threatening events, within 7 calendar days. In the latter case, a follow-up report was filed within 8 calendar days. Adverse reactions will be managed according to the standard clinical management practices. All adverse events and adverse reactions were reported to the PI within 24 hours.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention | Intervention group received ) intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| TENSION PYOTHORAX | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Eyal cohen | Hospital for Sick Children | 416-813-7654 | eyal.cohen@sickkids.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 29, 2017 | Mar 16, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 12, 2017 | Mar 16, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D016724 | Empyema, Pleural |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D004653 | Empyema |
| D013492 | Suppuration |
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| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| D003851 | Deoxyribonucleases |
| C568813 | dornase alfa |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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| OTHER |
| The Physicians' Services Incorporated Foundation | OTHER |
| McMaster Children's Hospital | OTHER |
| British Columbia Children's Hospital | OTHER |
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|
| 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 |
|
|
| Placebo | Other | Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg) |
|
|
Time from drain insertion to drain removal. |
| up to 4 months |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Mortality | Mortality from any cause during the hospitalization for empyema. | up to 4 months |
| Vancouver |
| British Columbia |
| BC V6H 3N1 |
| Canada |
| McMaster Children's Hospital | Hamilton | Ontario | L8N 3Z5 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H 8L1 | Canada |
| The Hospital for Sick Children(SickKids) | Toronto | Ontario | M5G 1X8 | Canada |
| CHU Sainte Justine | Montreal | Quebec | H3T 1C5 | Canada |
| Derived |
| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Participants |
|
|
| Secondary | Time to Meeting Discharge Criteria | Time from insertion of the chest drain to meeting discharge criteria. Discharge criteria:
| Posted | Mean | Standard Deviation | days | up to 4 months |
|
|
|
| Secondary | Time to Drain Removal | Time from drain insertion to drain removal. | Posted | Mean | Standard Deviation | days | 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. | Posted | Mean | Standard Deviation | days | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Mean | Standard Deviation | 2018 US $ | up to 4 months |
|
|
|
| Secondary | Mortality | Mortality from any cause during the hospitalization for empyema. | Posted | Count of Participants | Participants | up to 4 months |
|
|
|
| Other Pre-specified | 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. | Degree of opacification on chest radiography prior to chest tube removal | Posted | Count of Participants | Participants | 7 days after drain removal |
|
|
|
| 0 |
| 49 |
| 6 |
| 49 |
| 8 |
| 49 |
| EG001 | Control | Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline | 0 | 48 | 8 | 48 | 13 | 48 |
| Serious bleeding | Blood and lymphatic system disorders | Systematic Assessment |
|
| Bronchopleural fistula | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hemothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Low hemoglobin levels | Blood and lymphatic system disorders | Systematic Assessment |
|
| Septic shock | Blood and lymphatic system disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Edema | General disorders | Systematic Assessment |
|
| Transient chest pain | Cardiac disorders | Systematic Assessment |
|
| Herpes simplex virus infection | Immune system disorders | Systematic Assessment |
|
| Mild bleeding | Blood and lymphatic system disorders | Systematic Assessment |
|
| Kinked chest tube | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Low albumin | Endocrine disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Other bacterial infection | Immune system disorders | Systematic Assessment |
|
| Chest tube removed accidentally | General disorders | Systematic Assessment |
|
| Elevated potassium | Endocrine disorders | Systematic Assessment |
|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Urinary infection | Renal and urinary disorders | Systematic Assessment |
|
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| D010995 |
| Pleural Diseases |
| D012140 | Respiratory Tract Diseases |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
| D004950 | Esterases |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| 51-75% |
|
| >75% |
|
| Missing |
|