Malignant Pleural Effusion
Conditions
Keywords
malignant pleural effusion
Brief summary
The purpose of this study is to determine whether a new catheter is safe and effective in treating malignant pleural effusions compared to approve catheter.
Interventions
DEVICEActive Comparator: Approved Uncoated PleurX Indwelling Pleural Catheter
DEVICEExperimental: Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC)
Sponsors
C. R. Bard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Male or female, at least 18 years of age, inclusive. 2. Subject has a symptomatic MPE requiring intervention. For an effusion to be defined as malignant, at least one of the following must be true: 1. There is histocytological confirmation of pleural malignancy 2. The effusion is an exudate (per Light's criteria) in the context of histocytologically proven malignancy elsewhere, with no other clear cause for fluid identified. 3\. Subject has a history of at least 1 ipsilateral pleural effusion causing dyspnea that responded to thoracentesis where the lung expanded and the dyspnea was improved. 4\. Subject is willing and able to provide written informed consent. 5. Subject is willing and able to meet all study requirements, including follow-up visits and receiving study-related telephone calls. 6\. Subject has sufficient pleural fluid to allow safe insertion of an IPC. 7. Subject has negative pregnancy test if appropriate. 8. Subject or caregiver is able to perform home drainage of the pleural effusion (a caregiver can be a friend, family member or paid healthcare professional and applies to US sites only; UK subjects will have drainage managed by home-care nurses).
Exclusion criteria
* 1\. Subject has significant trapped lung, or a proximal bronchial obstruction which is likely to lead to trapped lung. For a subject to be eligible for this study, 2 separate study center clinicians must agree that there is no significant trapped lung on the same CXR using visual estimation (reference guide). The CXR used to make this decision must have been performed ≤30 days preceding the consent form being signed, and must have been performed preferably on the same day, but no more than 7 calendar days after a pleural drainage. Significant trapped lung is deemed present if any 1 of the following criteria is met: 1. A CXR shows hydropneumothorax. 2. A CXR shows ≥20% of the affected hemithorax to be free of the expected lung parenchymal markings and there is no suggestion of pleural fluid. 3. A CXR shows ≥20% of the affected hemithorax to be occupied with pleural fluid AFTER a pleural aspiration which resulted in symptoms suggestive of trapped lung (e.g., chest pain or cough). 2\. Subject has a Karnofsky score \<50, or a World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) performance status ≥3. Subjects who have a performance status of 3 may be considered for the study if the removal of their fluid would likely improve their performance score by 1 or more. 3\. Subject is pregnant, planning to become pregnant, or is lactating. 4. Subject has a history of empyema. 5. Subject has a history of chylothorax. 6. Subject has an uncorrected coagulopathy. 7. Subject has a hypersensitivity to new or existing pleural catheter or it's components. 8\. Subject has evidence, in the opinion of the Investigator, of either on-going systemic or pleural infection. 9\. Subject has had a lobectomy or pneumonectomy on the side of the effusion. 10. Subject has undergone a previous attempt at ipsilateral pleurodesis which has failed. 11\. Subject has previously been diagnosed with a serious immunodeficiency disorder. 12\. Subject has bilateral pleural effusions, with both being at least moderate in size (greater than one-third of the hemithorax on CXR). 13\. Subject has evidence of fluid loculation such that attempts at pleurodesis are likely to be futile. 14\. Subject has a mediastinal shift of ≥2 cm toward the side of the effusion. 15. Subject is receiving concurrent intrapleural chemotherapy or radiation therapy to the ipsilateral chest. 16\. Subject has any clinical condition, diagnosis, or social circumstance that, in the opinion of the Investigator, would mean participation in the study would be contraindicated. 17\. Subject has no access to a telephone. 18. Subject has no documented blood values (complete blood count \[CBC\], coagulation tests, urea and electrolytes, and liver function tests \[LFTs\]) within the last 10 days. 19\. Subject has previously participated in any clinical trial with the investigational device. 20\. Subject currently enrolled in any other clinical investigation or who has participated in any clinical investigation in the 30 days prior to starting this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Proportion of Subjects Achieving Pleurodesis Without Recurrence. | 30 days post catheter insertion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Confirmed Pleurodesis | 30 days post insertion | — |
| Time to Recurrence | 90 days post insertion | This endpoint was meant to measure time to recurrence; however, only 1 participant (in the SNCIPC group) had a recurrence so this outcome could not be analyzed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Empyema and Cellulitis | 90 days | — |
| Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 14, Day 30, Day 60, Day 90 | — |
| Pain Using 100 mm Visual Analog Scale (VAS) | Baseline,Day 7, 14, 30, 45, 75, and 90 | Chest pain was measured using a 100 mm VAS scale at baseline and at each subsequent visit. The resulting VAS score ranges from 0 to 100, with 0 indicating No pain and 100 indicating Very severe pain. Therefore, the lower the number, the less chest pain the subject is feeling at the time. |
| Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | 30 days. | — |
| Incidence of IPC Occlusion | 90 days | — |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC)
Experimental: Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | 81 |
| Approved Uncoated PleurX Indwelling Pleural Catheter Approved Uncoated PleurX Indwelling Pleural Catheter
Active Comparator: Approved Uncoated PleurX Indwelling Pleural Catheter | 38 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 30 | 7 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other, not specified | 6 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Approved Uncoated PleurX Indwelling Pleural Catheter | Total |
|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 10.95 | 66.7 years STANDARD_DEVIATION 10.35 | 65.4 years STANDARD_DEVIATION 10.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 10 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 | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 66 Participants | 34 Participants | 100 Participants |
| Region of Enrollment United Kingdom | 17 participants | 9 participants | 26 participants |
| Region of Enrollment United States | 64 participants | 29 participants | 93 participants |
| Sex/Gender, Customized Gender Female | 45 Participants | 23 Participants | 68 Participants |
| Sex/Gender, Customized Gender Male | 35 Participants | 15 Participants | 50 Participants |
| Sex/Gender, Customized Gender Missing | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 30 / 77 | 7 / 37 |
| other Total, other adverse events | 48 / 77 | 25 / 37 |
| serious Total, serious adverse events | 56 / 77 | 20 / 37 |
Outcome results
Primary
The Proportion of Subjects Achieving Pleurodesis Without Recurrence.
Time frame: 30 days post catheter insertion
Population: All participants who successfully had the catheter placed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | The Proportion of Subjects Achieving Pleurodesis Without Recurrence. | 17 Participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | The Proportion of Subjects Achieving Pleurodesis Without Recurrence. | 12 Participants |
Secondary
Time to Confirmed Pleurodesis
Time frame: 30 days post insertion
Population: Participants who had catheter successfully inserted
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Time to Confirmed Pleurodesis | 11.4 days | Standard Deviation 14.44 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Time to Confirmed Pleurodesis | 18.7 days | Standard Deviation 19.3 |
Secondary
Time to Recurrence
This endpoint was meant to measure time to recurrence; however, only 1 participant (in the SNCIPC group) had a recurrence so this outcome could not be analyzed.
Time frame: 90 days post insertion
Population: Participants who had catheter successfully inserted
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Time to Recurrence | 1 Participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Time to Recurrence | 0 Participants |
Other Pre-specified
Incidence of Empyema and Cellulitis
Time frame: 90 days
Population: Participants with successfully placed catheter
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Incidence of Empyema and Cellulitis | 3 Participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Incidence of Empyema and Cellulitis | 2 Participants |
Other Pre-specified
Incidence of IPC Occlusion
Time frame: 90 days
Population: Participants with successfully placed catheter
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Incidence of IPC Occlusion | 15 Participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Incidence of IPC Occlusion | 1 Participants |
Other Pre-specified
Pain Using 100 mm Visual Analog Scale (VAS)
Chest pain was measured using a 100 mm VAS scale at baseline and at each subsequent visit. The resulting VAS score ranges from 0 to 100, with 0 indicating No pain and 100 indicating Very severe pain. Therefore, the lower the number, the less chest pain the subject is feeling at the time.
Time frame: Baseline,Day 7, 14, 30, 45, 75, and 90
Population: Participants with successfully placed catheter
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Baseline | 22.7 units on a scale | Standard Deviation 26.63 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 7 | 16.9 units on a scale | Standard Deviation 26.78 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 14 | 9.8 units on a scale | Standard Deviation 16.62 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 30 | 10.0 units on a scale | Standard Deviation 18.53 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 45 | 8.4 units on a scale | Standard Deviation 17.84 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 60 | 10.7 units on a scale | Standard Deviation 22.74 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 75 | 7.4 units on a scale | Standard Deviation 19.97 |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Pain Using 100 mm Visual Analog Scale (VAS) | Day 90 | 9.6 units on a scale | Standard Deviation 18.41 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 90 | 9.2 units on a scale | Standard Deviation 23.21 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Baseline | 18.0 units on a scale | Standard Deviation 26.74 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 45 | 8.6 units on a scale | Standard Deviation 19.68 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 7 | 10.3 units on a scale | Standard Deviation 20.46 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 75 | 6.4 units on a scale | Standard Deviation 17.3 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 14 | 4.6 units on a scale | Standard Deviation 7.82 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 60 | 12.9 units on a scale | Standard Deviation 26.48 |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Pain Using 100 mm Visual Analog Scale (VAS) | Day 30 | 10.2 units on a scale | Standard Deviation 19.72 |
Other Pre-specified
Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others).
Time frame: 30 days.
Population: Participants with successfully placed catheter
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | Lung Cancer | 0.2222 proportion of participants |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | Breast Cancer | 0.2000 proportion of participants |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | Other Cancer | 0.2273 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | Lung Cancer | 0.4545 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | Breast Cancer | 0.1429 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Subjects With Confirmed Pleurodesis and Without Recurrence 30 Days After IPC Placement by Cancer Type (Lung, Breast and Others). | Other Cancer | 0.3158 proportion of participants |
Other Pre-specified
Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days.
Time frame: Day 14, Day 30, Day 60, Day 90
Population: Participants with catheter successfully placed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 14 | 0.2222 proportion of participants |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 30 | 0.3019 proportion of participants |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 60 | 0.3261 proportion of participants |
| Silver Nitrate Coated Indwelling Pleural Catheter (SNCIPC) | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 90 | 0.2500 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 90 | 0.5000 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 14 | 0.2162 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 60 | 0.4286 proportion of participants |
| Approved Uncoated PleurX Indwelling Pleural Catheter | Proportion of Surviving Subjects Without a Trapped Lung Diagnosis Following IPC Placement Who Have Confirmed Pleurodesis Without Recurrence at 14, 30, 60, 90 Days. | Day 30 | 0.3333 proportion of participants |