Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion

Our plain-English summary of Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion, by D.B. Fitzgerald, C. Sidhu, C. Budgeon, et al (Trials, 2022).

The study

• Authors: D.B. Fitzgerald, C. Sidhu, C. Budgeon, A.L. Tan, C.A. Read, B.C.H. Kwan, N.A. Smith, E.T. Fysh, S. Muruganandan, T. Saghaie, R. Shrestha, A. Badiei, P. Nguyen, A. Burke, J. Goddard, M. Windsor, J. McDonald, G. Wright, K. Czarnecka, P. Sivakumar, K. Yasufuku, D.J. Feller-Kopman, N.A. Maskell, K. Murray, Y.C.G. Lee
• Journal: Trials
• Published: 2022;23(1):530
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery.

Methods And Analysis: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months.

Ethics And Dissemination: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings.

Discussion: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms.

Trial Registration: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018.

Protocol Version: Version 3.00/4.02.19.

© 2022. The Author(s).

In plain English

This study protocol described a planned trial and reported no results. AMPLE-3 was a multi-centre, open-labelled randomised trial at hospitals in Australia, New Zealand, Canada and the UK. It compares two treatments for malignant pleural effusion, which is fluid around the lung caused by cancer. One is an indwelling pleural catheter, with talc through it if suitable. The other is VATS (video-assisted thoracoscopic surgery) pleurodesis. Eligible adults had symptomatic malignant pleural effusion, a predicted survival over 6 months and ECOG performance status 0 to 1. Patients scoring 2 or more could be included if draining the fluid was expected to improve this to 1 or better. They were to be assigned 1:1, balanced for cancer type (mesothelioma vs non-mesothelioma), previous pleurodesis, and trapped lung where known. The main outcome was needing a therapeutic same-side procedure for symptomatic return of the effusion within 12 months. The authors planned 158 patients to detect re-intervention rates of 5% with optimised catheter treatment versus 25% with VATS. These were assumptions based on previous studies. Investigators and patients could not be blinded. The authors expected the first evidence-based guidance for patients suitable for both treatments.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Study protocol for a multi-centre, open-labelled randomised trial (no results reported). The primary outcome is the need for an ipsilateral pleural intervention (surgical procedure, chest drain insertion or thoracentesis with therapeutic intent) within 12 months of randomisation for symptomatic recurrence of pleural effusion.
• Who was studied: Planned enrolment of 158 adults with symptomatic malignant pleural effusion, predicted survival of more than 6 months and ECOG performance status 0 to 1. Patients with performance status 2 or more may be included if removing the fluid is expected to improve it to 1 or better. Patients are recruited at tertiary centres in Australia, New Zealand, Canada and the UK. Recruitment began 23 April 2019, with estimated completion 31 December 2024. The sample size was calculated to detect a 5% reintervention rate in optimised IPC vs 25% in VATS, based on previous studies.
• Exposure: Not an asbestos exposure study. The trial compares two treatments: an indwelling pleural catheter (IPC), with talc slurry instilled via the catheter if suitable, versus VATS pleurodesis. Randomisation is minimised for mesothelioma vs non-mesothelioma, previous pleurodesis (vs not), and trapped lung, if known (vs not known).
• The authors' conclusion: The authors stated that the results of the trial will provide the first objective evidence-based guidance on which treatment is best for patients suitable for both interventions.
• Limitations the authors state:
  • Investigators and patients cannot be blinded to the treatment arms.
  • Complete blinding of data analysts will be difficult because the two treatments have very different outcome profiles.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Indwelling Pleural Catheter, Talc Pleurodesis, Video-Assisted Thoracoscopic Surgery (VATS), Quality of Life, Talc, Pleurodesis, Performance Status.

Related studies

• Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters — M. Azzopardi, R. Thomas, et al. (2016)
• Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial — S. Muruganandan, M. Azzopardi, et al. (2018)
• MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial — C. Matthews, C. Freeman, et al. (2019)
• Indwelling pleural catheter versus talc pleurodesis for malignant pleural effusion: a meta-analysis — M. Yeung, E.W. Loh, et al. (2020)
• Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma — E. Lim, L. Darlison, et al. (2020)
• The MesoVATS trial: is there a future for video-assisted thoracoscopic surgery partial pleurectomy? — R.C. Rintoul (2015)

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