AMPLE-3: IPC Plus Talc vs VATS in Management of Malignant Pleural Effusion (AMPLE-3)

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Respiratory Disease; Malignant Pleural Effusion
• Intervention / Treatment: Device: Indwelling pleural catheter (with talc pleurodesis if suitable); Procedure: Pleurodesis via Video-assisted thoracoscopic surgery

Detailed Description

Participants will be randomly assigned (1:1) to one of two arms:

Arm 1: Indwelling pleural catheter (with talc pleurodesis if suitable) Arm 2: Pleurodesis via Video-assisted thoracoscopic surgery

Arm 1: Indwelling pleural catheter is a long-term catheter that is tunnelled under the skin and allows ongoing drainage of pleural fluid by the patient or carer at home. It is inserted using local anaesthetic with or without sedation depending on local practice. An experienced respiratory physician inserts the catheter. Once the catheter is inserted, the pleural fluid will be evacuated as completely as possible. If the lung fully re-expands and there is no contraindication to talc pleurodesis, 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. 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. At review in clinic on day 14 (+/- 2 days), 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. All participants will remain under the care of their study doctors who are also their usual physicians, after the end of the study.

Arm 2: 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.

Participants in both arms will be reviewed at the same time points - at discharge, 14 days post-procedure, monthly to 6 months, then 3-monthly to 1 year. The reviews will include quality of life and breathlessness questionnaires.

All data will be obtained by the designated study research team who will carry out the IPC insertions and where VATs pleurodesis is undertaken, the research team will liaise directly with the study surgeon.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: YC Gary Lee, MBChB PhD; Phone Number: +61861510913; Email: gary.lee@uwa.edu.au
• Study Contact Backup: Name: Calvinjit Sidhu, MBBS; Phone Number: +61437672808; Email: calvinjit.sidhu@health.wa.gov.au

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Institute for Respiratory Health
      • Contact: YC Gary Lee, MBChB PhD; Phone Number: +61861510913; Email: gary.lee@uwa.edu.au
      • Contact: Calvinjit Sidhu, MBBS; Phone Number: +61437672808; Email: calvinjit.sidhu@health.wa.gov.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Device: 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.
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.	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Participants will be followed for a maximum of 12 months or until death if sooner.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	The study is for 12 months or until death if prior.
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.	The study is for 12 months or until death if prior.
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.	The study is for 12 months or until death if prior.
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.	Scores will be recorded daily for 28 days, then monthly to 6 months and 3-monthly until 12 months.
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.	Scores will be recorded daily for 28 days, monthly to 6 months and then 3-monthly to 12 months
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.	QoL will be measured at baseline, day 7-10 post-procedure, then monthly to 6 months then 3 monthly to 12 months.
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.	Monthly to 12 months at lead site only.
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.	Assessed continuously up to 12 months.
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.	From randomisation up to 12 months
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.	The study is for 12 months or until death if prior.

Collaborators and Investigators

• Sponsor: The University of Western Australia
• Collaborators: Johns Hopkins University; Vanderbilt University Medical Center; Guy's and St Thomas' NHS Foundation Trust; Universiti Kebangsaan Malaysia Medical Centre; St Vincent's Hospital Melbourne; The Prince Charles Hospital; Wellington Hospital; Toronto General Hospital; Auckland City Hospital; Concord Hospital; Sir Charles Gairdner Hospital; Hospital Queen Elizabeth, Malaysia; Fiona Stanley Hospital; Royal Adelaide Hospital, Australia; The Sutherland and St George Hospitals, Australia; Hollywood Private Hospital, Australia; Northern Hospital, Australia; St John of God Midland Hospital, Australia; St John of God Murdoch Hospital, Australia; Sunshine Coast Hospital and Health Service; John Hunter Hospital; Westmead Hospital, Australia; Wesley Hospital, Australia

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Respiration Disorders; Respiratory Tract Diseases; Pleural Effusion, Malignant; Pleural Effusion
• Other Study ID Numbers: AMPLE-3; ACTRN12618001013257 (Other Identifier: ANZCTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No