Can Talc Pleurodesis for Malignant Pleural Effusion be Performed on an Ambulatory Basis
Phase: NA
Conditions: Malignant Pleural Effusion, Malignancy, Palliative Care
Sponsor: David Rollins

Feasibility of ambulatory pleurodesis                                                                       
 
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PROTOCOL 
 
 
 
 
 
 
 
 
 
 
 
Study Title: 
Feasibility of ambulatory pleurodesis                                                    
Chief Investigator: 
Kevin Conroy 
Sponsor: 
TVRA 
Funder: 
TVRA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Feasibility of ambulatory pleurodesis                                                                       
 
Protocol V2 
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TABLE OF CONTENTS: 
1. Study Summary 
2. Trial Background 
3. Objectives and Study End Points 
 Primary Objective 
 Secondary Objectives 
 Primary Outcome Measure 
 Secondary Outcome Measures 
4. Overview of study pathway 
5. Selection of Patients 
 Inclusion Criteria 
 Exclusion Criteria 
 Screening and Informed Consent 
 Screening Logs 
6. Study Procedures 
7. Data Collection 
 Case Report Form  
8. Data Management & Confidentiality 
 Confidentiality 
 Missing Data and Data Queries 
9. Safety Reporting 
 Definitions of Adverse Events 
 Reporting Procedures 
10. Trial Management & Sponsor Oversight 
 Trial Management Group 
 Sponsorship and Monitoring Arrangements 
11. Withdrawal of Patients from Trial 
 Handling withdrawal requests 
 Use of data following withdrawal 
12. Trial Funding 
13. Publication and Dissemination Plans 
14. References & Bibliography  
 

Feasibility of ambulatory pleurodesis                                                                       
 
Protocol V2 
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1. STUDY SUMMARY: 
 
Overall Aim:  
Is the study protocol deliverable? 
Primary Objective: 
 Can patients with malignant pleural effusions 
undergo chest drainage and talc. Pleurodesis 
on an ambulatory basis 
Secondary Objective 
 What are the patient perspectives of this 
protocol? 
Target Accrual: 
10 patients 
Inclusion 
& 
Exclusion 
Criteria: 
Inclusion 
 Malignant pleural effusion 
 Life expectancy >30 days 
 WHO PS 1-2 (3 if due to exertional dyspnoea) 
 
Exclusion 
 Previous failed pleurodesis 
 Known non-expansile lung 

Feasibility of ambulatory pleurodesis                                                                       
 
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 Pregnancy 
 Age <18 
Data Collection Summary: 
  
Anticipated 
Duration 
of 
Recruitment 
12 months 
Duration of Patient Follow-
up 
30 days 
Definition of End of Trial 
Drain removal and completion of d+30 questionnaire 
 
 
2. BACKGROUND 
 
AIMS AND OUTCOMES:  
Patients with malignant pleural disease often experience a significant symptom burden and 
a short life expectancy. The cornerstone of their treatment is relieving breathlessness by 
draining fluid from around the lungs and attempting to prevent further fluid build up. 
Inpatient chest drainage and talc pleurodesis remains the most successful method of 
stopping the fluid build up but this often requires an average hospital stay of four days. This 
can be an inappropriate length of time for this patient group. Our study would investigate 
whether this treatment could be provided on an ambulatory basis and facilitate a greater 
quality of life. 
  
We would assess deliverability of the trial protocol and collect patient feedback to see if our 
patients consider it an acceptable and worthwhile intervention. 
 
3. Primary Objective 
Can patients with malignant pleural effusions undergo chest drainage and talc. Pleurodesis 
on an ambulatory basis 
 
Secondary Objective 
What are the patient perspectives of this protocol? 
 
Primary Outcome Measure: 
Success delivery of study protocol 
 
Secondary Outcome Measure: 
Patient questionnaire  
 

Feasibility of ambulatory pleurodesis                                                                       
 
Protocol V2 
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4. OVERVIEW OF STUDY PATHWAY:  
Eligible patients will be offered enrolment in the trial along with standard of care options. 
 
If patients agree to participate in the trial they would be consented for chest drain, talc 
pleurodesis on an ambulatory pathway.  
 
On day 1: 
 A standard chest drain would be inserted in the morning and large volume fluid 
removal would commence using an underwater seal bottle- as per standard care. We 
would remove 1000mls of fluid (stopping earlier if not tolerated) and the clamp the 
drain for one hour.  
 We would then open the drain again and drain up to 500mls before again clamping 
for one hour.  
 We would repeat this process as frequently as possible until the end of the working 
day.  
 The drain would then be connected to an ambulatory bag and left in the open 
position.  
 The patient would then be sent home to return on day 2.    
 
On day 2: 
 The drain would be flushed, aspirated and the output assessed.  
 If there is still fluid output we would drain up to 500mls and close the drain for an 
hour and repeat. 
  If there is no further output we would arrange a chest x ray to ensure the effusion 
has resolved and the lung has fully inflated.  
 If it has we would proceed to talc slurry instillation (with 20mls 1% lidocaine as per 
standard practice) and clamp the drain for 2 hours.  
 After this we would open the drain again and drain up to 500mls and close the drain 
for an hour.  
 We would repeat this as required and again the patient would return home with an 
ambulatory bag left open.  
 If the effusion has resolved but the lung has not fully expanded due to underlying 
disease then we would simply remove the chest drain as pleurodesis will not be 
possible. 
 
On day 3: 
 The drain would be flushed, aspirated and the output assessed. 
  If there is still fluid output we would drain up to 500mls and close the drain for an 
hour and repeat. 
  If there is no further output we would arrange a chest x ray to ensure the effusion 
has resolved. 

Feasibility of ambulatory pleurodesis                                                                       
 
Protocol V2 
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  We would then remove the drain and repeat the x-ray to confirm there have been 
no complications.  
 We would then consider the intervention complete and revert to standard care   
 
If there was still significant fluid output we would repeatedly drain 500ml volumes of fluid 
and clamp the drain for an hour after each 500ml until dry. 
 
We would ask patients to complete a very brief questionnaire (visual analogue scale) on 
breathlessness and chest pain on day 1 - before intervention, 1 hour post drain insertion, at 
the end of the day and on day 2 and 3 on first encounter and at the end of the day. We 
would also repeat the questionnaire on day 30 along with their satisfaction with the 
protocol. 
 
 
 
5. SELECTION OF PATIENTS: 
 
Inclusion criteria: 
 Malignant pleural effusion 
 Life expectancy >30 days 
 WHO PS 0-2 (3 if due to exertional dyspnoea) 
 
Patient exclusion criteria: 
 Previous failed pleurodesis 
 Known non-expansile lung 

Feasibility of ambulatory pleurodesis                                                                       
 
Protocol V2 
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CI: K Conroy 
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 Pregnancy 
 Age <18 
 
Screening and Informed Consent: 
 
Potential candidates will be referred to the respiratory (pleural) team for standard care. 
Eligible candidates will be offered trial enrolment as an additional option by the PI/CI or 
delegates and undergo written consent. 
 
SAMPLE SIZE 
 
Number of participants and records  
10 patients 
 
Statistical analysis plan  
Thematic analysis of patient feedback 
 
 
6. STUDY PROCEDURES 
 
Study protocol outlined above. Additionally, we will collect Patient related outcome 
measures relating to breathlessness and pain each day and at day +30. We will also seek 
patient feedback on the protocol at this point. 
 
7. DATA COLLECTION 
 
Data will be collected by the trials team longitudinally. Patients surveys will be collected and 
the 30 day survey will be conducted via telephone consultant or face to face by the trial 
team 
 
8. DATA MANAGEMENT AND CONFIDENTIALITY 
 
Investigators are required to maintain on file the accurate, complete, and current  records 
relating to this Study. Data will be stored securely in a locked office in a trial file. Digital 
information will be stored on an NHS computer in a locked office. Only authorized personnel 
and their designees will have access to these confidential files. 
 
 
PROTOCOL DEVIATIONS 
 
Protocol deviations should be reported to the sponsor and Chief Investigator using the 
provided reporting form. The Sponsor and Chief Investigator should then review the details 

Feasibility of ambulatory pleurodesis                                                                       
 
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to assess the impact on the research dataset and also to assess if there are learning points 
to help prevent a repeat deviation.   
 
MISSING DATA AND DATA QUERIES 
 
Missing data will be included in the analysis. The trials team, CI or an appropriate designee 
will address any emergent data queries.  
 
9. SAFETY REPORTING 
 
Definitions  
Adverse Event (AE) Any untoward medical occurrence in a participant, including 
occurrences  which are not necessarily caused by or related to the intervention under 
study.  
Adverse Reaction (AR) An untoward or unintended response in a participant to which is 
related to  the intervention under study i.e. that a causal relationship between the trial  
intervention and an AE is at least a reasonable possibility and the  relationship cannot be 
ruled out.  
All cases judged by either the reporting medically qualified professional or   
the Sponsor as having a reasonable suspected causal relationship to the trial   
intervention qualify as adverse reaction. 
 
Serious adverse Event (SAE) is any untoward medical occurrence that; results in death, is life 
threatening  or requires inpatient hospitalisation. 
 
 
Serious adverse reaction (SAR) is an event that is both serious and in the opinion of the 
investigator, believed with reasonable probability to be due to the trial intervention.   
Unexpected Serious  Adverse Reaction (USAR)  is a  serious adverse reaction, the nature 
and severity of which is not  consistent with the known information about the intervention 
under study. 
 
 9.2. Recording and Reporting AEs and SAEs  
For each SAE the following information will be collected:  

Feasibility of ambulatory pleurodesis                                                                       
 
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∙ Full details in medical terms and case description  
∙ Event duration (start and end dates, if applicable)  
∙ Action taken  
∙ Outcome  
∙ Seriousness criteria  
∙ Causality in the opinion of the investigator  
∙ Whether the event is considered expected or unexpected.  
Any change of condition or other follow-up information should be faxed to the  
[Sponsor/GCTU] as soon as it is available or at least within 24 hours of the  information 
becoming available. Events will be followed up until the event has  resolved or a final 
outcome has been reached.  
9.3. Recording and Reporting USARs  
All USARs occurring from the intervention until 6 months post termination of trial  
treatment must be reported to the NHS REC. The Sponsor will perform this  reporting. 
The assessment of expectedness will be performed by the PI against the known  
information for the trial. USARs must be reported no later than 15 calendar days after 
the Sponsor has first  knowledge of the event. Any relevant follow-up information 
should be sought and reported as soon as possible after the initial report. As soon as a 
site suspects that a SAR may be a USAR they must contact the CI,  sponsor 
representative and the trial manager immediately. The reporting  timeframe starts at 
day 0 when the Sponsor is in receipt of a minimum set of  information:   
∙ Sponsor trial reference and trial name  
∙ Patient trial number and date of birth  
∙ Date of notification of the event  
∙ Medical description of the event  
∙ Date and time of the onset of the event (including event end date if  applicable)  
∙ Causality assessment   
∙ Seriousness of the event, particularly if life threatening or fatal   
∙ An identifiable reporter (e.g., Principal Investigator)  
This information must be provided on USAR report form. The site is expected to fully 
cooperate with the Sponsor in order that a full and detailed report can be  submitted to 
the NHS REC within the required timelines.  
PIs will be informed of all USARs by the Sponsor and CI.  

Feasibility of ambulatory pleurodesis                                                                       
 
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Responsibilities  
Principal Investigator  
∙ Checking for AEs and ARs when participants attend for treatment or follow up  
∙ Using medical judgement in assigning seriousness and causality and  providing an 
opinion on expectedness of events.  
∙ Ensuring that all SAEs and SARs, including USARs, are recorded and reported  to the 
Sponsor within 24 hours of becoming aware of the event and provide  further follow-up 
information as soon as available.   
∙ Ensuring that AEs and ARs are recorded and reported to the Sponsor in line  with the 
requirements of the protocol.  
Chief Investigator  
∙ Clinical oversight of the safety of trial participants, including an ongoing  review of the 
risk/benefit.  
∙ Using medical judgement in assigning seriousness, causality and  expectedness of SAEs 
where it has not been possible to obtain local medical  assessment.  
∙ Using medical judgement in assigning expectedness to SARs.  
∙ Immediate review of all USARs. 
∙ Review of specific SAEs and SARs in accordance with the trial risk assessment  and 
protocol.  
Sponsor  
∙ Assessment of expectedness of any USARs  
∙ Expedited reporting of USARs to the REC within required timelines 
∙Notification of all investigator sites of any USAR that occurs  
  
9.6. Reporting Urgent Safety Measures  
An Urgent Safety Measure (USM) is an action that the Sponsor or an Investigator  may take 
in order to protect the subjects of a trial against any immediate hazard  to their health or 
safety. Upon implementation of an USM by an Investigator, the Sponsor must be notified 
immediately and details of the USM given. The Sponsor must inform the NHS REC within 3 
days of the USM taking place in accordance  with the Sponsor’s standard operating 
procedures.  
 
 
 
 

Feasibility of ambulatory pleurodesis                                                                       
 
Protocol V2 
IRAS: 330188 
CI: K Conroy 
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10. TRIAL MANAGEMENT AND OVERSIGHT 
 
The monitoring team employs a risk-based approach to monitoring. This approach focuses 
efforts on the most crucial data and process elements to allow for more efficient monitoring 
practices while maintaining the quality of the overall study conduct. 
 
The team will employ remote monitoring of clinical trial with a focus on 
safety, study endpoints, data completion and data outliers. Source documentation, 
including study logs, Informed Consent Log, Protocol Violation/Deviation Log and the 
Serious Adverse Event Report log will monitored to ensure that the sites are adhering to the 
study protocol and procedures.  
 
In collaboration with the data management team, the monitor will create and utilize reports 
outlining data totality and timeliness, missing values to generate queries and optimize 
reconciliation of data.  
 
Clinical sites will maintain copies of all source documents, which may be either paper or 
electronic, at each site. The monitors will review the source documents to determine 
whether the data reported is complete and accurate. They will also verify that all adverse 
events exist on the source documents, are consistent with the protocol, and are 
documented in the appropriate format.  
 
Source documents include medical charts, initial hospital admission reports, operative 
procedure records, discharge and re-admission reports, consult notes and other 
study-related notes. At an on-site visit, the study monitors reserve the right to copy de-
identified records in support of all adverse events and outcomes. 
 
The monitors will also confirm that the regulatory binder is complete and that all associated 
documents are up to date. The regulatory binder should include but is not limited to all 
revisions of the protocol and informed consent, approvals for all of the above documents, 
and correspondence; investigator’s agreement and agreement amendments; DOA log;, CVs 
and appropriate training certificates of all study personnel and monitor site visit log.  
 
If problems are identified during the monitoring visit missing study documents, etc., the 
monitor will assist the site in resolving the issues.  
 
 
11. WITHDRAWAL OF PATIENTS FROM THE TRIAL 
 
Participants are free to withdraw from the trial at any point and return to stand care. This 
can be done by contacting the trial team in writing, telephone or in person. Patient 
information up to that point would be included with patient consent. We would also seek to 
record the reasons for their withdrawal with their consent. 

Feasibility of ambulatory pleurodesis                                                                       
 
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12. TRIAL FUNDING 
 
There is no specific funding sought for this trial due to the small sample size. 
 
 
13. DISSEMINATION 
 
Publication and presentations 
The results will be presented locally, nationally and internationally; where any personal 
information is necessary for the data analysis (use of demographic data) this will be 
presented in a way to ensure that individuals cannot be identified and the patients will be 
informed in advance of giving their consent to participate in the study.  
 
 
 
REFERENCES 
 
1. Davies HE, Mishra EK, Kahan BC, Wrightson JM, Stanton AE, Guhan A, Davies CW, Grayez J, Harrison R, Prasad 
A, Crosthwaite N, Lee YC, Davies RJ, Miller RF, Rahman NM. Effect of an indwelling pleural catheter vs chest 
tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 
randomized controlled trial. JAMA. 2012 Jun 13;307(22):2383-9. doi: 10.1001/jama.2012.5535. PMID: 
22610520.