Trial Outcomes & Findings for Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial) (NCT NCT01717742)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

97 participants

Primary outcome timeframe

up to 4 months

Results posted on

2020-04-14

Participant Flow

Participant milestones

Participant milestones
Measure	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)	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
Overall Study STARTED	48	49
Overall Study COMPLETED	43	47
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intervention (tPA & DNase) n=49 Participants Intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Placebo (tPA & Placebo) n=48 Participants Intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline	Total n=97 Participants Total of all reporting groups
Age, Categorical <=18 years	49 Participants n=5 Participants	48 Participants n=7 Participants	97 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	58.4 Months STANDARD_DEVIATION 43.3 • n=5 Participants	64.1 Months STANDARD_DEVIATION 44.2 • n=7 Participants	61.3 Months STANDARD_DEVIATION 45.6 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	21 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · First nations	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · African	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Asian/Pacific Islander	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · White	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Middle Eastern	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · South Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Prefer not to answer	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Canada	49 Participants n=5 Participants	48 Participants n=7 Participants	97 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 4 months

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

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Time to Hospital Discharge	9.0 days Standard Deviation 4.9	9.1 days Standard Deviation 5.3

SECONDARY outcome

Timeframe: up to 4 months

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

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Time to Meeting Discharge Criteria	8.2 days Standard Deviation 4.5	8.5 days Standard Deviation 5.4

SECONDARY outcome

Timeframe: up to 4 months

Time from drain insertion to drain removal.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Time to Drain Removal	6.9 days Standard Deviation 4.3	6.9 days Standard Deviation 5.3

SECONDARY outcome

Timeframe: up to 4 months

Duration of fever (defined as temperature \>38 degrees celsius taken by any method) from insertion of the chest drain until resolution.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Duration of Fever After Intervention	2.8 days Standard Deviation 3.4	3.3 days Standard Deviation 3.4

SECONDARY outcome

Timeframe: up to 4 months

Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention	9 Participants	8 Participants

SECONDARY outcome

Timeframe: up to 4 months

Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Number of Participants With Serious Bleeding	2 Participants	4 Participants

SECONDARY outcome

Timeframe: up to 4 months

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.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Number of Participants With Further Interventions	4 Participants	2 Participants

SECONDARY outcome

Timeframe: 3 months post-discharge

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.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Number of Participants With Hospital Readmission	2 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 4 months

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.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Cost of the Hospitalization	11329 2018 US $ Standard Deviation 7139	10760 2018 US $ Standard Deviation 5071

SECONDARY outcome

Timeframe: up to 4 months

Mortality from any cause during the hospitalization for empyema.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Mortality	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days after drain removal

Population: Degree of opacification on chest radiography prior to chest tube removal

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.

Outcome measures

Outcome measures
Measure	Intervention n=49 Participants Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 Participants Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Chest Radiography <=25%	33 Participants	25 Participants
Chest Radiography 26-50%	10 Participants	11 Participants
Chest Radiography 51-75%	1 Participants	4 Participants
Chest Radiography >75%	2 Participants	1 Participants
Chest Radiography Missing	3 Participants	7 Participants

Adverse Events

Intervention

Serious events: 6 serious events

Other events: 8 other events

Deaths: 0 deaths

Control

Serious events: 8 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Intervention n=49 participants at risk Intervention group received ) intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 participants at risk Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Respiratory, thoracic and mediastinal disorders TENSION PYOTHORAX	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
Blood and lymphatic system disorders Serious bleeding	4.1% 2/49 • Number of events 2 • 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.	8.3% 4/48 • Number of events 4 • 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.
Respiratory, thoracic and mediastinal disorders Bronchopleural fistula	4.1% 2/49 • Number of events 2 • 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.	0.00% 0/48 • 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.
Respiratory, thoracic and mediastinal disorders Hemothorax	2.0% 1/49 • Number of events 1 • 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.	2.1% 1/48 • Number of events 1 • 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.
Blood and lymphatic system disorders Low hemoglobin levels	0.00% 0/49 • 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.	4.2% 2/48 • Number of events 2 • 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.
Blood and lymphatic system disorders Septic shock	0.00% 0/49 • 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.	2.1% 1/48 • Number of events 1 • 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.

Other adverse events

Additional Information

Dr. Eyal cohen

Hospital for Sick Children

Phone: 416-813-7654

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Intervention n=49 participants at risk Intervention group received ) intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg	Control n=48 participants at risk Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline
Gastrointestinal disorders Nausea	0.00% 0/49 • 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.	4.2% 2/48 • Number of events 2 • 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.
Skin and subcutaneous tissue disorders Rash	0.00% 0/49 • 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.	4.2% 2/48 • Number of events 2 • 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.
Gastrointestinal disorders Constipation	2.0% 1/49 • Number of events 1 • 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.	4.2% 2/48 • Number of events 2 • 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.
General disorders Edema	0.00% 0/49 • 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.	4.2% 2/48 • Number of events 2 • 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.
Cardiac disorders Transient chest pain	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
Immune system disorders Herpes simplex virus infection	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
Blood and lymphatic system disorders Mild bleeding	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
Respiratory, thoracic and mediastinal disorders Kinked chest tube	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
Endocrine disorders Low albumin	2.0% 1/49 • Number of events 1 • 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.	2.1% 1/48 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Pruritus	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
Immune system disorders Other bacterial infection	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/48 • 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.
General disorders Chest tube removed accidentally	0.00% 0/49 • 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.	2.1% 1/48 • Number of events 1 • 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.
Endocrine disorders Elevated potassium	0.00% 0/49 • 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.	2.1% 1/48 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	0.00% 0/49 • 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.	2.1% 1/48 • Number of events 1 • 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.
Renal and urinary disorders Urinary infection	0.00% 0/49 • 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.	2.1% 1/48 • Number of events 1 • 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.