Pleural Effusion
Conditions
Brief summary
Prospective Randomized Double-Blind Controlled Trial of Intrapleural Fibrinolytic Therapy to Enhance Chemical Pleurodesis versus Standard of care Talc therapy in patients with recurrent pleural effusion.
Detailed description
This protocol describes a prospective, randomized, double-blind controlled trial comparing TSP alone to the combination of TSP with cathflo activase for achieving optimal results with pleurodesis for recurrent pleural effusion. Patients who sign informed consent will be randomly assigned to receive either TSP alone (talc, 5 gm in 50 ml NS) with placebo (50 ml NS) or TSP with cathflo activase (4 mg in 50 ml NS) through the chest pleural catheter. Follow-up lasts for three months. The primary outcome is achievement of a Radiographically Satisfactory Pleurodesis (RSP) by day three post-procedure, defined as chest tube drainage of less than 100cc over 24 hours and a chest x-ray showing similar or less pleural space opacification than on the day TSP was performed (baseline, day 0). Secondary outcomes include the proportion of patients who achieve RSP, time needed to achieve RSP, duration of chest tube drainage, length of hospital stay after initiation of TSP, proportion of patients requiring repeat TSP, change in serum hemoglobin during therapy, objective assessments of pain and dyspnea, and potential complications. This study will recruit 136 patients, with an interim analyses for efficacy after 50 patients, and aims to help develop the future standard for management of patients requiring pleurodesis for their symptomatic pleural effusion.
Interventions
DRUGTalc Slurry Pleurodesis
Talc, 5 gm in 50 ml Normal Saline given through chest pleural catheter
DRUGCathflo Activase
Cathflo Activase 4mg in 50ml normal saline given through chest pleural catheter
Sponsors
Genentech, Inc.
Memorial Healthcare System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind. Pharmacist will be unblinded.
Intervention model description
single center, prospective, randomized, double-blind, placebo-controlled trial with two arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \> 18 years 2. Symptomatic pleural effusion requiring intervention 3. Expected survival \> 3 months 4. Written informed consent to trial participation
Exclusion criteria
1. Females who are pregnant or lactating 2. Inability to obtain consent from the patient or patient's designated representative. 3. Inability of the patient to comply with the protocol. 4. Previously documented adverse reaction to talc or cathflo activase. 5. Oral or intravenous steroid therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chest X-ray Results on Day 3 After Pleurodesis | 3-5 days | Evaluate whether the chest x-ray is better (+1), the same (0), or worse (-1) than it was on the day of pleurodesis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dyspnea on Day 3 After Pleurodesis | 3 days | Borg dyspnea scale complete by patient on day 3 after pleurodesis, on a scale of 0 to 10, with 10 being worst. |
| Pain Score | 3 days | Visual analog scale for self-reported level of pain at three days after pleurodesis, from 0 to 100 with 100 being worst pain. |
| Chest Tube Size | day 1 | Size of the chest tube used for pleural fluid drainage and talc slurry pleurodesis |
| Time to Chest Tube Removal | Days from pleurodesis to chest tube removal | Number of days from pleurodesis to removal of the last chest tube |
| Pleural Drainage Volume (mL) After Pleurodesis | 3 days | Total volume of drainage on days 1-3 after pleurodesis |
| Radiographically Satisfactory Pleurodesis | days | Number (proportion) of patients who achieved daily chest tube drainage of less than 100 cc/24 hours, with the chest x-ray showing no evidence of accumulation of pleural fluid since pleurodesis. |
| Time to Achieve Radiographically Satisfactory Pleurodesis | days | Days from pleurodesis to the point at which pleurodesis is deemed successful and complete |
| 30 Day Mortality | 30 days from pleurodesis | Number of patients who died within 30 days of pleurodesis |
| Length of Stay | days | Total duration of hospital stay from admission to discharge, including time before pleurodesis |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo Patients who sign informed consent may be randomized to receive talc slurry pleurodesis (TSP) alone (talc, 5 gm in 50 ml NS) with placebo (50 ml Normal saline (NS)) through the chest pleural catheter.
Talc Slurry Pleurodesis: Talc, 5 gm in 50 ml Normal Saline given through chest pleural catheter | 12 |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase Patients who sign informed consent may be randomized to receive talc slurry pleurodesis (TSP) (Talc, 5mg in 50ml Normal saline (NS)) with cathflo activase (4 mg in 50 ml NS) through the chest pleural catheter
Cathflo Activase: Cathflo Activase 4mg in 50ml normal saline given through chest pleural catheter
Talc Slurry Pleurodesis: Talc, 5 gm in 50 ml Normal Saline given through chest pleural catheter | 15 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Talc Slurry Pleurodesis (TSP) Plus Placebo | Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Total |
|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 14.5 | 64.6 years STANDARD_DEVIATION 15.8 | 65.7 years STANDARD_DEVIATION 14.9 |
| BMI | 23.5 kg/m^2 STANDARD_DEVIATION 3.1 | 24.8 kg/m^2 STANDARD_DEVIATION 4.5 | 24.2 kg/m^2 STANDARD_DEVIATION 3.9 |
| Chest pain Visual Analog Scale (VAS) | 23.3 Scale from 0 to 100; with 100 worst pain STANDARD_DEVIATION 32.4 | 11.9 Scale from 0 to 100; with 100 worst pain STANDARD_DEVIATION 28.2 | 17.6 Scale from 0 to 100; with 100 worst pain STANDARD_DEVIATION 30.2 |
| Dyspnea score | 0.9 units on a scale from 0 to 10, 10 worst STANDARD_DEVIATION 1.2 | 0.5 units on a scale from 0 to 10, 10 worst STANDARD_DEVIATION 1.5 | 0.7 units on a scale from 0 to 10, 10 worst STANDARD_DEVIATION 1.3 |
| Effusion etiology Liver disease | 1 Participants | 0 Participants | 1 Participants |
| Effusion etiology Lung cancer | 4 Participants | 4 Participants | 8 Participants |
| Effusion etiology Other malignant | 6 Participants | 9 Participants | 15 Participants |
| Effusion etiology Unknown | 1 Participants | 2 Participants | 3 Participants |
| Effusion laterality Bilateral | 3 Participants | 2 Participants | 5 Participants |
| Effusion laterality Left | 4 Participants | 3 Participants | 7 Participants |
| Effusion laterality Right | 5 Participants | 10 Participants | 15 Participants |
| Effusion size Large (>1000 ml) | 2 Participants | 4 Participants | 6 Participants |
| Effusion size Moderate (500 - 1000 ml) | 2 Participants | 6 Participants | 8 Participants |
| Effusion size Small (<500 ml) | 8 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 10 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Prior pleural intervention | 11 Participants | 14 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 22 Participants |
| Region of Enrollment United States | 12 participants | 15 participants | 27 participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 16 Participants |
| Sex: Female, Male Male | 8 Participants | 3 Participants | 11 Participants |
| Trapped lung | 4 Participants | 8 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 11 | 5 / 14 |
| other Total, other adverse events | 0 / 11 | 0 / 14 |
| serious Total, serious adverse events | 0 / 11 | 0 / 14 |
Outcome results
Primary
Chest X-ray Results on Day 3 After Pleurodesis
Evaluate whether the chest x-ray is better (+1), the same (0), or worse (-1) than it was on the day of pleurodesis
Time frame: 3-5 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest X-ray Results on Day 3 After Pleurodesis | Worse | 5 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest X-ray Results on Day 3 After Pleurodesis | Same | 5 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest X-ray Results on Day 3 After Pleurodesis | Better | 2 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest X-ray Results on Day 3 After Pleurodesis | Worse | 6 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest X-ray Results on Day 3 After Pleurodesis | Same | 8 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest X-ray Results on Day 3 After Pleurodesis | Better | 1 Participants |
p-value: 0.863Fisher Exact
Secondary
30 Day Mortality
Number of patients who died within 30 days of pleurodesis
Time frame: 30 days from pleurodesis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | 30 Day Mortality | 4 participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | 30 Day Mortality | 5 participants |
p-value: 1Fisher Exact
Secondary
Chest Tube Size
Size of the chest tube used for pleural fluid drainage and talc slurry pleurodesis
Time frame: day 1
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest Tube Size | 10 Fr | 4 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest Tube Size | 12 Fr | 4 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest Tube Size | 14 Fr | 2 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Chest Tube Size | Unknown | 2 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest Tube Size | Unknown | 5 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest Tube Size | 10 Fr | 4 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest Tube Size | 14 Fr | 2 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Chest Tube Size | 12 Fr | 4 Participants |
p-value: 0.809Fisher Exact
Secondary
Dyspnea on Day 3 After Pleurodesis
Borg dyspnea scale complete by patient on day 3 after pleurodesis, on a scale of 0 to 10, with 10 being worst.
Time frame: 3 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Dyspnea on Day 3 After Pleurodesis | 1 score on a scale from 0 to 10 |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Dyspnea on Day 3 After Pleurodesis | 1 score on a scale from 0 to 10 |
Comparison: Borg dyspnea scale day 3 post-TSPp-value: 0.891Wilcoxon (Mann-Whitney)
Secondary
Length of Stay
Total duration of hospital stay from admission to discharge, including time before pleurodesis
Time frame: days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Length of Stay | 10 days |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Length of Stay | 11 days |
p-value: 0.808Wilcoxon (Mann-Whitney)
Secondary
Pain Score
Visual analog scale for self-reported level of pain at three days after pleurodesis, from 0 to 100 with 100 being worst pain.
Time frame: 3 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Pain Score | 10 score on a scale from 0 to 100 |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Pain Score | 10 score on a scale from 0 to 100 |
Comparison: Pain score at day 3 post-TSPp-value: 0.899Wilcoxon (Mann-Whitney)
Secondary
Pleural Drainage Volume (mL) After Pleurodesis
Total volume of drainage on days 1-3 after pleurodesis
Time frame: 3 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Pleural Drainage Volume (mL) After Pleurodesis | Day 1 | 125 ml |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Pleural Drainage Volume (mL) After Pleurodesis | Day 2 | 39 ml |
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Pleural Drainage Volume (mL) After Pleurodesis | Day 3 | 45 ml |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Pleural Drainage Volume (mL) After Pleurodesis | Day 1 | 427.5 ml |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Pleural Drainage Volume (mL) After Pleurodesis | Day 2 | 150 ml |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Pleural Drainage Volume (mL) After Pleurodesis | Day 3 | 100 ml |
Comparison: Difference in pleural drainage volume day 1 post-TSPp-value: 0.005Wilcoxon (Mann-Whitney)
Secondary
Radiographically Satisfactory Pleurodesis
Number (proportion) of patients who achieved daily chest tube drainage of less than 100 cc/24 hours, with the chest x-ray showing no evidence of accumulation of pleural fluid since pleurodesis.
Time frame: days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Radiographically Satisfactory Pleurodesis | 8 Participants |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Radiographically Satisfactory Pleurodesis | 12 Participants |
p-value: 0.662Fisher Exact
Secondary
Time to Achieve Radiographically Satisfactory Pleurodesis
Days from pleurodesis to the point at which pleurodesis is deemed successful and complete
Time frame: days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Time to Achieve Radiographically Satisfactory Pleurodesis | 5.75 days | Standard Deviation 6.27 |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Time to Achieve Radiographically Satisfactory Pleurodesis | 4.83 days | Standard Deviation 3.43 |
p-value: 0.714t-test, 2 sided
Secondary
Time to Chest Tube Removal
Number of days from pleurodesis to removal of the last chest tube
Time frame: Days from pleurodesis to chest tube removal
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talc Slurry Pleurodesis (TSP) Plus Placebo | Time to Chest Tube Removal | 7 days |
| Talc Slurry Pleurodesis (TSP) Plus Cathflo Activase | Time to Chest Tube Removal | 9 days |
p-value: 0.946Wilcoxon (Mann-Whitney)