Clinical trial NCT04322136: AMPLE-3: IPC Plus Talc vs VATS in Management of Malignant Pleural Effusion
Official 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Malignant Pleural Effusion
Respiratory Disease
Cancer
Lead sponsor: The University of Western Australia
Sponsor class: OTHER
Collaborators: name: Sir Charles Gairdner Hospital
name: Fiona Stanley Hospital
name: The Sutherland and St George Hospitals, Australia
name: Hollywood Private Hospital, Australia
name: Wellington Hospital
name: Northern Hospital, Australia
name: Concord Hospital
name: Royal Adelaide Hospital, Australia
name: St John of God Midland Hospital, Australia
name: St John of God Murdoch Hospital, Australia
name: Westmead Hospital, Australia
name: St Vincent's Hospital Melbourne
name: The Prince Charles Hospital
name: Sunshine Coast Hospital and Health Service
name: Guy's and St Thomas' NHS Foundation Trust
name: Toronto General Hospital
name: Universiti Kebangsaan Malaysia Medical Centre
name: Hospital Queen Elizabeth, Malaysia
name: Johns Hopkins University
name: John Hunter Hospital
name: Wesley Hospital, Australia
name: Auckland City Hospital
name: Vanderbilt University Medical Center
First posted: 2020-03-26
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Need for an ipsilateral pleural intervention
timeFrame: Participants will be followed for a maximum of 12 months or until death if sooner.
Secondary outcomes:
measure: Need for repeat ipsilateral pleural intervention including diagnostic aspiration
timeFrame: The study is for 12 months or until death if prior.
measure: Time to symptomatic effusion recurrence
timeFrame: The study is for 12 months or until death if prior.
measure: All-cause hospital days
timeFrame: The study is for 12 months or until death if prior.
measure: Degree of breathlessness
timeFrame: Scores will be recorded daily for 28 days, then monthly to 6 months and 3-monthly until 12 months.
measure: Pain scale
timeFrame: Scores will be recorded daily for 28 days, monthly to 6 months and then 3-monthly to 12 months
measure: Quality of Life (QoL)
timeFrame: QoL will be measured at baseline, day 7-10 post-procedure, then monthly to 6 months then 3 monthly to 12 months.
measure: Physical activity patterns
timeFrame: Monthly to 12 months at lead site only.
measure: Adverse events from time of enrolment
timeFrame: Assessed continuously up to 12 months.
measure: Overall survival from randomisation.
timeFrame: From randomisation up to 12 months
measure: Pleural-related hospital days.
timeFrame: The study is for 12 months or until death if prior.
Other outcomes:
Locations:
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
state: Western Australia
Study officials:
References: