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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04322136




Registration number
NCT04322136
Ethics application status
Date submitted
24/03/2020
Date registered
26/03/2020
Date last updated
26/03/2020

Titles & IDs
Public title
AMPLE-3: IPC Plus Talc vs VATS in Management of Malignant Pleural Effusion
Scientific title
The Australasian Malignant PLeural Effusion (AMPLE) Trial - 3: A Randomised Study of the Relative Benefits of Combined Indwelling Pleural Catheter (IPC) and Talc Pleurodesis Therapy or Video-Assisted Thoracoscopic Surgery (VATS) in the Management of Patients With Malignant Pleural Effusion.
Secondary ID [1] 0 0
ACTRN12618001013257
Secondary ID [2] 0 0
AMPLE-3
Universal Trial Number (UTN)
Trial acronym
AMPLE-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Effusion 0 0
Respiratory Disease 0 0
Cancer 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Pleurodesis via Video-assisted thoracoscopic surgery
Treatment: Devices - Indwelling pleural catheter (with talc pleurodesis if suitable)

Other: IPC (with talc pleurodesis if suitable) - The patients will undertake daily drainage to day 14 post insertion. The drainage will either be performed by the participant's carer or nurses in the community. A bottle or bag will be attached to the drain to allow for removal of accumulated pleural fluid. Once completed the drain will be reattached to the pleural catheter.
Participants will be taught how to perform pleural drainage by the main study doctor at the hospital or a specialist nurse. They will drain their own IPCs at home with the either the help of a family member or friend or have access to community nursing support systems.

Other: Pleurodesis via VATS - Participants will undergo VATS within two weeks of randomisation. VATS is usually performed in an operating theatre, using either general anaesthesia or local anaesthesia with sedation. The pleural fluid will be removed and adhesions can be divided (adhesiolysis). Assessment of lung re-expansion will be performed intra-operatively. If lung re-expansion is adequate (as judged by the operating surgeon), a variety of techniques may be employed to induce a pleurodesis, including, but not limited to, talc poudrage and mechanical abrasion. Decortication may be performed if deemed appropriate and feasible by the operating surgeon. A chest drain will be left in situ after the surgery. Post-operative care will be administered as per local practice.


Treatment: Surgery: Pleurodesis via Video-assisted thoracoscopic surgery
Video-assisted thoracoscopic surgery is a type of key-hole surgery performed under general anaesthetic and usually single lung ventilation by a cardio-thoracic surgeon. This is expected to take about 1 hour. Between one and three ports are used to insert a camera and instruments into the chest cavity. Adhesions can be broken down if present and the lining of the lung (visceral pleura) can sometimes be removed (decortication) to facilitate lung re-expansion. The surgeon can then perform either mechanical abrasion or talc poudrage to induce inflammation and subsequent pleurodesis. A chest drain is left in situ post-operatively and is removed when the fluid draining is below a certain volume depending on local practice.

Treatment: Devices: Indwelling pleural catheter (with talc pleurodesis if suitable)
Once the indwelling pleural catheter is inserted, the pleural fluid will be evacuated as completely as possible. If the lung fully re-expands, 4-5g of sterile graded talc will be instilled via the IPC. The participant will then be discharged on a daily drainage regimen for 14 days. At review in clinic on day 14, the participant will be assessed for spontaneous pleurodesis (<50ml drainage on 3 consecutive drainage attempts). If pleurodesis has occurred and there is no residual symptomatic effusion, arrangements will be made for IPC removal. Otherwise the participant will switch to a symptom-guided drainage regimen. If the lung does not fully re-expand following complete fluid evacuation, they will be discharged on a symptom-guided regimen without instillation of talc. The drainage regimen will continue for the duration of the study and beyond if pleurodesis has not occurred and pleural fluid continues to accumulate.

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Need for an ipsilateral pleural intervention - Proportion of participants requiring an ipsilateral (on the same side) pleural procedure for management of symptomatic re-accumulation of pleural fluid including surgical procedure, chest drain insertion, attempted therapeutic thoracentesis. This is a composite outcome.
Data will be obtained from the participants and the hospital record.
Timepoint [1] 0 0
Participants will be followed for a maximum of 12 months or until death if sooner.
Secondary outcome [1] 0 0
Need for repeat ipsilateral pleural intervention including diagnostic aspiration - Proportion of participants requiring an ipsilateral pleural procedure including diagnostic aspirate.
Data will be obtained from the participants and the hospital record.
Timepoint [1] 0 0
The study is for 12 months or until death if prior.
Secondary outcome [2] 0 0
Time to symptomatic effusion recurrence - Time to effusion recurrence - will be assessed using chest x-ray and ultrasound at each visit. Recurrent effusion is defined as greater than 25% opacity on chest x-ray on the side of the intervention as judged by two independent clinicians and evidence of pleural fluid on ultrasound.
Timepoint [2] 0 0
The study is for 12 months or until death if prior.
Secondary outcome [3] 0 0
All-cause hospital days - Length of stay post-procedure and hospitalization for any cause (except for elective admissions for chemotherapy) will be recorded for all patients post randomisation. Admissions will be analysed as total admission days and also pleural-related admission days.
The data will be collected from participants and the hospital records.
Timepoint [3] 0 0
The study is for 12 months or until death if prior.
Secondary outcome [4] 0 0
Degree of breathlessness - Degree of breathlessness will be measured by a 100mm Visual Analogue Scale (VAS). The VAS is a 100mm line anchored with "no breathlessness" at 0mm and "worst breathlessness imaginable" at 100mm.
Timepoint [4] 0 0
Scores will be recorded daily for 28 days, then monthly to 6 months and 3-monthly until 12 months.
Secondary outcome [5] 0 0
Pain scale - Pain will be assessed using a 100mm visual analogue scale. The 100mm horizontal line will be anchored with "no pain" at 0mm and "worst pain imaginable" at 100mm.
Timepoint [5] 0 0
Scores will be recorded daily for 28 days, monthly to 6 months and then 3-monthly to 12 months
Secondary outcome [6] 0 0
Quality of Life (QoL) - Quality of Life (QoL) will be measured using two instruments: EQ-5D-5L is a standardised measure of HRQoL that comprises five dimensions including mobility, self-care, usual activities, pain//discomfort and anxiety/depression. VAS QoL records self-rated health on a 100mm line anchored with "best imaginable health state" at 0mm and "worst imaginable health state" at 100mm.
Timepoint [6] 0 0
QoL will be measured at baseline, day 7-10 post-procedure, then monthly to 6 months then 3 monthly to 12 months.
Secondary outcome [7] 0 0
Physical activity patterns - Actigraphy is one part of the study and is an outcome comprising a few different factors. Physical activity patterns, vigorous activity and periods of sedentary behaviour, will be evaluated by a well validated triaxial accelerometer (ActiGraph GT3X+, Pensacola, FL, USA). Objective physical activity patterns will be assessed by 7-day triaxial accelerometer assessment providing an indication of functional status. The Actigraph device is reliable, with excellent test-retest reproducibility in cancer research and rated as 'user friendly' by both healthy and patient populations.
Timepoint [7] 0 0
Monthly to 12 months at lead site only.
Secondary outcome [8] 0 0
Adverse events from time of enrolment - Adverse events from randomization until end of follow-up or death. An adverse event is defined as any participant-reported or medical records complications associated with the IPC or VATS pleurodesis, such as pleural infection, cellulitis, pain, symptomatic loculation, tube blockage, catheter tract metastases, parenchymal air leak etc., and any peri/post-procedural complications such as prolonged air-leak, atelectasis, pneumonia, cardiovascular complications, acute kidney injury or drop in haemoglobin requiring transfusion.
Timepoint [8] 0 0
Assessed continuously up to 12 months.
Secondary outcome [9] 0 0
Overall survival from randomisation. - Overall Survival will be recorded from date of enrolment to death or end of study follow-up. Survival difference between IPC and VATS management of malignant pleural effusion has not been previously studied.
Timepoint [9] 0 0
From randomisation up to 12 months
Secondary outcome [10] 0 0
Pleural-related hospital days. - Pleural-related hospital days. Length of stay post-procedure and hospitalization for any cause (except for elective admissions for chemotherapy) will be recorded for all patients post randomisation. Admissions will be analysed as total admission days and also pleural-related admission days.
The data will be collected from participants and the hospital records.
Timepoint [10] 0 0
The study is for 12 months or until death if prior.

Eligibility
Key inclusion criteria
1. Patients with a symptomatic MPE*

2. Predicted survival of more than 6 months

3. Eastern Cooperative Oncology Group (ECOG) score = Peformance status defined as a
patient's level of functioning in terms of their ability to care for themselves, daily
activity, and physical ability (walking, working, etc. ECOG 0-1 (or ECOG greater than
or equal to 2 if it is felt that removal of pleural fluid would improve their status
to 0 or 1).

- MPE is defined as histologically/cytologically proven pleural malignancy or an
otherwise unexplained pleural effusion in the context of clinically proven cancer
elsewhere.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age <18yrs;

2. Unfit to undergo a surgical procedure (American Society of Anaesthesiologists Score
>/=4); 3. Pleural infection;

4. Chylothorax; 5. Pregnancy or lactation; 6. Uncorrectable bleeding diathesis; 7. Previous
ipsilateral lobectomy/pneumonectomy; 8. Inability to consent or comply with protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Institute for Respiratory Health - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Western Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Sir Charles Gairdner Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Fiona Stanley Hospital, Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
The Sutherland and St George Hospitals, Australia
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Hollywood Private Hospital, Australia
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Wellington Hospital
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Northern Hospital, Australia
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Concord Hospital
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Royal Adelaide Hospital
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
St John of God Midland Hospital, Australia
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
St John of God Murdoch Hospital, Australia
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
St John of God Subiaco Hospital, Australia
Address [11] 0 0
Country [11] 0 0
Other collaborator category [12] 0 0
Other
Name [12] 0 0
St Vincent's Hospital Melbourne
Address [12] 0 0
Country [12] 0 0
Other collaborator category [13] 0 0
Other
Name [13] 0 0
The Prince Charles Hospital
Address [13] 0 0
Country [13] 0 0
Other collaborator category [14] 0 0
Other
Name [14] 0 0
Sunshine Coast Hospital and Health Service
Address [14] 0 0
Country [14] 0 0
Other collaborator category [15] 0 0
Other
Name [15] 0 0
Guy's and St Thomas' NHS Foundation Trust
Address [15] 0 0
Country [15] 0 0
Other collaborator category [16] 0 0
Other
Name [16] 0 0
Toronto General Hospital
Address [16] 0 0
Country [16] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine if an indwelling catheter is more effective than
surgical pleurodosis in treating malignant pleural effusion.

Who is it for?

You may be eligible for this study if you are an adult who is suffering from symptomatic
proven pleural malignancy or an otherwise unexplained pleural effusion.

Study details

Consenting participants will be randomised to one of two treatment arms:

- Arm 1: Indwelling pleural catheter. A long term catheter is inserted under the skin in
order to allow ongoing drainage of the pleural fluid. Participants will then be
instructed to undergo a daily drainage regimen for 14 days at home.

- Arm 2: Surgical pleurodesis. Participants under a key-hole surgery to remove fluid and
facilitate lung re-expansion.

Participants will then be followed up at discharge, 14 days, monthly for 6 months and then
every 3 months up to one year post-procedure. These visits will include completion of Quality
of Life questionnaires, a chest xray, an ultrasound (if thought necessary) and if you are at
the lead site (Sir Charles Gairdner Hospital) a review of your Actigraphy logs up to 6 months
after discharge.

It is hoped this research will help to provide effective symptom control with minimal
intervention for those with malignant pleural effusion.
Trial website
https://clinicaltrials.gov/show/NCT04322136
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
YC Gary Lee, MBChB PhD
Address 0 0
Country 0 0
Phone 0 0
+61861510913
Fax 0 0
Email 0 0
gary.lee@uwa.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04322136