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

Abstract

IntroductionMalignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.Methods and analysisA multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0–1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate.Ethics and disseminationThe Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberACTRN12615000963527; Pre-results.

Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single‐centre experience

“…Results of the Seal‐Mpe trial were published very recently showing safety and feasibility data on the potential use of such devices . Whether daily IPC drainage could increase IPC treatment success compared with drainage guided by symptoms is currently under assessment in the multicentre randomized AMPLE‐2 trial . Because corticosteroids are known to interfere with pleurodesis and the use of corticosteroids is frequent in malignant disease, the use of systemic corticosteroids from 48 h before until 24 h after pleurodesis was assessed.…”

Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial

“…The Australasian Malignant PLeural Effusion (AMPLE) Trial-2 was a multi-centered, openlabelled, randomized clinical trial (RCT) designed to address the equipoise between Aggressive (daily) versus Symptom-guided approaches to IPC drainage in patients with a MPE, specifically their efficacy in breathlessness control, induction of pleurodesis, improvement of QoL and the associated hospitalization and complication rates. 7…”

Inter‐observer variation in image interpretation and the prognostic importance of non‐expansile lung in malignant pleural effusion

“…Radiographic detection of NEL is therefore an important factor in the planning of MPE treatment, and is routinely used as an eligibility criterion, stratification factor and/or treatment determinant in MPE trials. However, there are limited data supporting the use of NEL in this manner, particularly with regard to inter‐observer agreement, which should be high if single observers are used…”

“…However, in this study, a significant number of patients failed screening due to radiographically defined NEL (41/339, 12%), while an additional 32 of 250 (13%) of those recruited could not receive talc due to NEL that subsequently became apparent. 3 Radiographic detection of NEL is therefore an important factor in the planning of MPE treatment, and is routinely used as an eligibility criterion, 4 stratification factor 5 and/or treatment determinant 6 in MPE trials. However, there are limited data supporting the use of NEL in this manner, particularly with regard to interobserver agreement, which should be high if single observers are used.…”