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

The University of Western Australia

Status: Enrolling

Conditions: Respiratory Disease; Cancer; Malignant Pleural Effusion

Treatments: Device: Indwelling pleural catheter (with talc pleurodesis if suitable); Procedure: Pleurodesis via Video-assisted thoracoscopic surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT04322136

AMPLE-3

ACTRN12618001013257 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 2 patient groups

IPC (with talc pleurodesis if suitable)

Other group

Description:

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.

Treatment:

Device: Indwelling pleural catheter (with talc pleurodesis if suitable)

Pleurodesis via VATS

Other group

Description:

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:

Procedure: Pleurodesis via Video-assisted thoracoscopic surgery