A Phase 3 interventional study of TPA (Tissue Plasminogen Activator) and DNase in Pleural Empyema, sponsored by The Hospital for Sick Children. Completed at 6 sites in Canada. Open to participants aged 6 Months to 18 Years. Per ClinicalTrials.gov, last updated 2020-04-14.
Sponsored by The Hospital for Sick Children · Phase 3, Interventional, and Treatment
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.
33 studies on the registry are indexed under Empyema, Pleural; 11 are open to participants now.
This study's enrollment of 97 is above the median of 77 across 26 interventional studies indexed under Empyema, Pleural.
Browse Empyema, Pleural studies →The Hospital for Sick Children is the lead sponsor of 578 studies on the registry; 83 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 1 (14%) have results posted.
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hospitalized with diagnosis of pleural empyema requiring chest tube drainage with fibrinolytics as judged by the attending physician with the following criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: TPA (Tissue Plasminogen Activator) · Other: Placebo
Drug: TPA (Tissue Plasminogen Activator) · Drug: DNase
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)
Drug pages: Deoxyribonucleases · Deoxyribonuclease I
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)
Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (\>10 kg)
Also known as: Normal saline
Time to Hospital Discharge
Time from insertion of the chest drain to discharge from hospital.
Time frame: up to 4 months
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
Time frame: up to 4 months
Time to Drain Removal
Time from drain insertion to drain removal.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: up to 4 months
Mortality
Mortality from any cause during the hospitalization for empyema.
Time frame: up to 4 months
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.
Time frame: 7 days after drain removal
| Milestone | tPA (Tissue Plasminogen Activator) and Placebo | tPA (Tissue Plasminogen Activator) and DNase |
|---|---|---|
| Started | 48 | 49 |
| Completed | 43 | 47 |
| Not completed | 5 | 2 |
Time from insertion of the chest drain to discharge from hospital.
| days | Intervention | Control |
|---|---|---|
| Time to Hospital Discharge | 9.0 ± 4.9 | 9.1 ± 5.3 |
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
| days | Intervention | Control |
|---|---|---|
| Time to Meeting Discharge Criteria | 8.2 ± 4.5 | 8.5 ± 5.4 |
Time from drain insertion to drain removal.
| days | Intervention | Control |
|---|---|---|
| Time to Drain Removal | 6.9 ± 4.3 | 6.9 ± 5.3 |
Duration of fever (defined as temperature \>38 degrees celsius taken by any method) from insertion of the chest drain until resolution.
| days | Intervention | Control |
|---|---|---|
| Duration of Fever After Intervention | 2.8 ± 3.4 | 3.3 ± 3.4 |
Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.
| Participants | Intervention | Control |
|---|---|---|
| Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention | 9 | 8 |
Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.
| Participants | Intervention | Control |
|---|---|---|
| Number of Participants With Serious Bleeding | 2 | 4 |
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.
| Participants | Intervention | Control |
|---|---|---|
| Number of Participants With Further Interventions | 4 | 2 |
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.
| Participants | Intervention | Control |
|---|---|---|
| Number of Participants With Hospital Readmission | 2 | 0 |
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.
| 2018 US $ | Intervention | Control |
|---|---|---|
| Cost of the Hospitalization | 11329 ± 7139 | 10760 ± 5071 |
Mortality from any cause during the hospitalization for empyema.
| Participants | Intervention | Control |
|---|---|---|
| Mortality | 0 | 0 |
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.
| Participants | Intervention | Control |
|---|---|---|
| <=25% | 33 | 25 |
| 26-50% | 10 | 11 |
| 51-75% | 1 | 4 |
| >75% | 2 | 1 |
| Missing | 3 | 7 |
Collected over Over the course of the patient's hospitalization. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intervention | 0/49 (0%) | 6/49 (12.2%) | 8/49 (16.3%) |
| Control | 0/48 (0%) | 8/48 (16.7%) | 13/48 (27.1%) |
| Event | Intervention | Control |
|---|---|---|
| Serious bleedingBlood and lymphatic system disorders | 2/49 | 4/48 |
| Low hemoglobin levelsBlood and lymphatic system disorders | 0/49 | 2/48 |
| Bronchopleural fistulaRespiratory, thoracic and mediastinal disorders | 2/49 | 0/48 |
| HemothoraxRespiratory, thoracic and mediastinal disorders | 1/49 | 1/48 |
| Septic shockBlood and lymphatic system disorders | 0/49 | 1/48 |
| TENSION PYOTHORAXRespiratory, thoracic and mediastinal disorders | 1/49 | 0/48 |
| Event | Intervention | Control |
|---|---|---|
| NauseaGastrointestinal disorders | 0/49 | 2/48 |
| RashSkin and subcutaneous tissue disorders | 0/49 | 2/48 |
| ConstipationGastrointestinal disorders | 1/49 | 2/48 |
| EdemaGeneral disorders | 0/49 | 2/48 |
| Low albuminEndocrine disorders | 1/49 | 1/48 |
| Chest tube removed accidentallyGeneral disorders | 0/49 | 1/48 |
| Elevated potassiumEndocrine disorders | 0/49 | 1/48 |
| Upper respiratory infectionRespiratory, thoracic and mediastinal disorders | 0/49 | 1/48 |
| Urinary infectionRenal and urinary disorders | 0/49 | 1/48 |
| Transient chest painCardiac disorders | 1/49 | 0/48 |
| Age, Categorical(Participants) | Intervention (tPA & DNase) | Placebo (tPA & Placebo) | Total |
|---|---|---|---|
| <=18 years | 49 | 48 | 97 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(Months) | Intervention (tPA & DNase) | Placebo (tPA & Placebo) | Total |
|---|---|---|---|
| Mean | 58.4 ± 43.3 | 64.1 ± 44.2 | 61.3 ± 45.6 |
| Sex: Female, Male(Participants) | Intervention (tPA & DNase) | Placebo (tPA & Placebo) | Total |
|---|---|---|---|
| Female | 24 | 21 | 45 |
| Male | 25 | 27 | 52 |
| Race/Ethnicity, Customized(Participants) | Intervention (tPA & DNase) | Placebo (tPA & Placebo) | Total |
|---|---|---|---|
| Race/ethnicity — First nations | 0 | 2 | 2 |
| Race/ethnicity — African | 2 | 0 | 2 |
| Race/ethnicity — Asian/Pacific Islander | 14 | 13 | 27 |
| Race/ethnicity — White | 26 | 26 | 52 |
| Race/ethnicity — Hispanic | 1 | 0 | 1 |
| Race/ethnicity — Middle Eastern | 0 | 1 | 1 |
| Race/ethnicity — South Asian | 0 | 1 | 1 |
| Race/ethnicity — Prefer not to answer | 5 | 4 | 9 |
| Race/ethnicity — Missing | 1 | 1 | 2 |
| Region of Enrollment(Participants) | Intervention (tPA & DNase) | Placebo (tPA & Placebo) | Total |
|---|---|---|---|
| Canada | 49 | 48 | 97 |
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Studies of the drugs tested here: Deoxyribonucleases · Deoxyribonuclease I
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