Trial Outcomes & Findings for Efficacy and Safety of Activase (Ateplase) vs Placebo in Complicated Pleural Effusions (CPE)/Empyemas (NCT NCT00468104)
NCT ID: NCT00468104
Last Updated: 2012-04-30
Results Overview
CT scans of the chest and Chest X rays (CXR) were used to determine resolution of Pleural effusions/empyema/ pneumonia after 3 days of Alteplase/ Placebo therapy. If no response was noted with the first intervention patients were offered surgery --Decortiation/ Video Assisted Thoracic Surgery (VATS) or to receive the second intervention. Patients that failed the second intervention were offered surgery.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
100 participants
Primary outcome timeframe
patients were followed six weeks per protocol. Most patients treated with Alteplase were also followed for up to six months
Results posted on
2012-04-30
Participant Flow
Patients with loculated pleural effusions that failed to respond to chest tube placement and standard medical treatment and were considered for surgery were given the option to enter into a double blind cross over trial
108 patients were evaluated but only 100 entered the trial. 2 patients refused, 2 patients admitting physicians opted out of the trial, 3 patients chest tube removed inadvertently, 1 patient for coagulopathy
Participant milestones
| Measure |
Alteplase Then Placebo
25 mg of Alteplase in 100 cc of normal saline was instilled intrapleurally daily for three days. Chest CT scans were performed on the fourth day . If less than a 50% reduction in the pleural effusion was determined, the patient was given the option to go to surgery or to the second intervention of the trial (with Placebo)
|
Placebo Then Alteplase
Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days. Chest CT scans were performed on the fourth day . If less than a 50% reduction in the pleural effusion was determined, the patient was given the option to go to surgery or to the second intervention of the trial (with Alteplase)
|
|---|---|---|
|
First Intervention
STARTED
|
54
|
46
|
|
First Intervention
COMPLETED
|
45
|
45
|
|
First Intervention
NOT COMPLETED
|
9
|
1
|
|
Second Intervention
STARTED
|
8
|
41
|
|
Second Intervention
COMPLETED
|
3
|
37
|
|
Second Intervention
NOT COMPLETED
|
5
|
4
|
Reasons for withdrawal
| Measure |
Alteplase Then Placebo
25 mg of Alteplase in 100 cc of normal saline was instilled intrapleurally daily for three days. Chest CT scans were performed on the fourth day . If less than a 50% reduction in the pleural effusion was determined, the patient was given the option to go to surgery or to the second intervention of the trial (with Placebo)
|
Placebo Then Alteplase
Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days. Chest CT scans were performed on the fourth day . If less than a 50% reduction in the pleural effusion was determined, the patient was given the option to go to surgery or to the second intervention of the trial (with Alteplase)
|
|---|---|---|
|
First Intervention
Protocol Violation
|
2
|
1
|
|
First Intervention
bleeding at chest tube site--first dose
|
1
|
0
|
|
First Intervention
died within 3 weeks
|
1
|
0
|
|
First Intervention
malposition/blocked chest tube tube
|
2
|
0
|
|
First Intervention
large lung mass with minimal effusion
|
1
|
0
|
|
First Intervention
associated prolonged pneumothorax
|
1
|
0
|
|
First Intervention
trapped lung
|
1
|
0
|
|
Second Intervention
Withdrawal by Subject
|
5
|
2
|
|
Second Intervention
discarded for malposition of chest tube
|
0
|
2
|
Baseline Characteristics
Efficacy and Safety of Activase (Ateplase) vs Placebo in Complicated Pleural Effusions (CPE)/Empyemas
Baseline characteristics by cohort
| Measure |
Alteplase; Placebo
n=100 Participants
25mg of Alteplase in 100 cc of normal saline instilled intrapleurally; 100 cc of normal saline instilled intrapleurally
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
39 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
61 Participants
n=99 Participants
|
|
Age Continuous
|
67 years
STANDARD_DEVIATION 15 • n=99 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
100 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: patients were followed six weeks per protocol. Most patients treated with Alteplase were also followed for up to six monthsPopulation: intention to treat
CT scans of the chest and Chest X rays (CXR) were used to determine resolution of Pleural effusions/empyema/ pneumonia after 3 days of Alteplase/ Placebo therapy. If no response was noted with the first intervention patients were offered surgery --Decortiation/ Video Assisted Thoracic Surgery (VATS) or to receive the second intervention. Patients that failed the second intervention were offered surgery.
Outcome measures
| Measure |
Alteplase
n=81 Participants
25mg of Alteplase in 100 cc of normal saline given intrapleurally daily for 3 days either in the first or second arm
|
Placebo
n=47 Participants
Placebo in 100 cc of normal saline given daily intrapleurally for 3 days either in the first or second arm
|
|---|---|---|
|
No Surgical Intervention
|
66 participants
|
6 participants
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed
patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pneumonia
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 weeksPopulation: protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed
patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pleural effusion/empyema
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 weeksPopulation: protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed
patients were followed for 6 weeks and clinical symptoms of resolution of shortness of breath were documented
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 weeksPopulation: protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed
patients were followed for 6 weeks and resolution of sepsis was documented
Outcome measures
Outcome data not reported
Adverse Events
Received Alteplase Only
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Received Placebo Only
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Received Both Alteplase and Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Received Alteplase Only
n=42 participants at risk
These patients received only Alteplase and were not crossed over
|
Received Placebo Only
n=8 participants at risk
These patients received Placebo only and were not crossed over
|
Received Both Alteplase and Placebo
n=40 participants at risk
These patients were crossed over and received both Alteplase and Placebo
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
serious bleeding at the chest tube site
|
2.4%
1/42 • Number of events 1 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/8 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/40 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
|
General disorders
Shortness of breath, worsening sepsis
|
0.00%
0/42 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/8 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/40 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
Other adverse events
| Measure |
Received Alteplase Only
n=42 participants at risk
These patients received only Alteplase and were not crossed over
|
Received Placebo Only
n=8 participants at risk
These patients received Placebo only and were not crossed over
|
Received Both Alteplase and Placebo
n=40 participants at risk
These patients were crossed over and received both Alteplase and Placebo
|
|---|---|---|---|
|
General disorders
severe chest pain post drug instillation
|
2.4%
1/42 • Number of events 12 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/8 • Number of events 12 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
2.5%
1/40 • Number of events 12 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
|
General disorders
mild to moderate chest pain
|
14.3%
6/42 • Number of events 12 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
12.5%
1/8 • Number of events 12 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
7.5%
3/40 • Number of events 12 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
|
General disorders
hypotension and worsening renal function
|
0.00%
0/42 • Number of events 4 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/8 • Number of events 4 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
10.0%
4/40 • Number of events 4 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
|
Blood and lymphatic system disorders
blood loss--pleural fluid
|
7.1%
3/42 • Number of events 3 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/8 • Number of events 3 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/40 • Number of events 3 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
|
Respiratory, thoracic and mediastinal disorders
increasing shortness of breath
|
0.00%
0/42 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
25.0%
2/8 • Number of events 2 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/40 • Number of events 2 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
|
Infections and infestations
worsening sepsis
|
0.00%
0/42 • Number of events 2 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
25.0%
2/8 • Number of events 2 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
0.00%
0/40 • Number of events 2 • soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place