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

Our plain-English summary of Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial, by S. Muruganandan, M. Azzopardi, D.B. Fitzgerald, et al (The Lancet. Respiratory Medicine, 2018).

The study

• Authors: S. Muruganandan, M. Azzopardi, D.B. Fitzgerald, R. Shrestha, B.C.H. Kwan, D.C.L. Lam, C.C. De Chaneet, M.R.S. Rashid Ali, E. Yap, C.L. Tobin, L.A. Garske, P.T. Nguyen, C. Stanley, N.D. Popowicz, C. Kosky, R. Thomas, C.A. Read, C.A. Budgeon, D. Feller-Kopman, N.A. Maskell, K. Murray, Y.C.G. Lee
• Journal: The Lancet. Respiratory Medicine
• Published: 2018;6(9):671-680
• Type of article: Randomized trial
• Cited by: 167 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Indwelling pleural catheters are an established management option for malignant pleural effusion and have advantages over talc slurry pleurodesis. The optimal regimen of drainage after indwelling pleural catheter insertion is debated and ranges from aggressive (daily) drainage to drainage only when symptomatic.

Methods: AMPLE-2 was an open-label randomised trial involving 11 centres in Australia, New Zealand, Hong Kong, and Malaysia. Patients with symptomatic malignant pleural effusions were randomly assigned (1:1) to the aggressive (daily) or symptom-guided drainage groups for 60 days and minimised by cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group [ECOG] score 0-1 vs ≥2), presence of trapped lung, and prior pleurodesis. Patients were followed up for 6 months. The primary outcome was mean daily breathlessness score, measured by use of a 100 mm visual analogue scale during the first 60 days. Secondary outcomes included rates of spontaneous pleurodesis and self-reported quality-of-life measures. Results were analysed by an intention-to-treat approach. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000963527.

Findings: Between July 20, 2015, and Jan 26, 2017, 87 patients were recruited and randomly assigned to the aggressive (n=43) or symptom-guided (n=44) drainage groups. The mean daily breathlessness scores did not differ significantly between the aggressive and symptom-guided drainage groups (geometric means 13·1 mm [95% CI 9·8-17·4] vs 17·3 mm [13·0-22·0]; ratio of geometric means 1·32 [95% CI 0·88-1·97]; p=0·18). More patients in the aggressive group developed spontaneous pleurodesis than in the symptom-guided group in the first 60 days (16 [37·2%] of 43 vs five [11·4%] of 44, p=0·0049) and at 6 months (19 [44·2%] vs seven [15·9%], p=0·004; hazard ratio 3·287 [95% CI 1·396-7·740]; p=0·0065). Patient-reported quality-of-life measures, assessed with EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L), were better in the aggressive group than in the symptom-guided group (estimated means 0·713 [95% CI 0·647-0·779] vs 0·601 [0·536-0·667]). The estimated difference in means was 0·112 (95% CI 0·0198-0·204; p=0·0174). Pain scores, total days spent in hospital, and mortality did not differ significantly between groups. Serious adverse events occurred in 11 (25·6%) of 43 patients in the aggressive drainage group and in 12 (27·3%) of 44 patients in the symptom-guided drainage group, including 11 episodes of pleural infection in nine patients (five in the aggressive group and six in the symptom-guided drainage group).

Interpretation: We found no differences between the aggressive (daily) and the symptom-guided drainage regimens for indwelling pleural catheters in providing breathlessness control. These data indicate that daily indwelling pleural catheter drainage is more effective in promoting spontaneous pleurodesis and might improve quality of life.

Funding: Cancer Council of Western Australia and the Sir Charles Gairdner Research Advisory Group.

Copyright © 2018 Elsevier Ltd. All rights reserved.

In plain English

This randomised trial at 11 hospitals in Australia, New Zealand, Hong Kong and Malaysia did not study asbestos exposure. It compared two ways of draining cancer-related fluid around the lung (malignant pleural effusion) through a chest tube left in place (an indwelling pleural catheter). Between July 2015 and January 2017, 87 adults were assigned for 60 days to daily drainage (43) or to symptom-guided drainage (44), whose catheters were also checked at least fortnightly. Of the 87, 29 had mesothelioma. Average daily breathlessness scores did not differ significantly between the groups. Within 60 days, fluid stopped forming (spontaneous pleurodesis) in 16 of 43 daily-drainage patients and 5 of 44 symptom-guided patients. Quality-of-life index scores were better with daily drainage; a second quality-of-life scale showed no statistically significant difference. Pain, hospital days, deaths and serious complications did not differ significantly. The authors reported no difference in results between patients with and without mesothelioma. They concluded that both approaches controlled breathlessness, and that daily drainage promoted spontaneous pleurodesis and might improve quality of life. They noted that patient-reported measures in an open-label study could be biased.

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: Randomised, multicentre, open-label trial comparing two drainage regimens
• Who was studied: 87 adults with symptomatic malignant pleural effusion needing an indwelling pleural catheter, recruited from July 20, 2015, to Jan 26, 2017, at 11 centres in Australia, New Zealand, Hong Kong and Malaysia. Median age was 66.8 years; there were 41 men and 46 women. The most common cancers were lung cancer (34), mesothelioma (29) and ovarian carcinoma (10).
• Exposure: No asbestos exposure was studied. The trial compared two drainage regimens over the first 60 days. One group (n=43) drained daily (aggressive drainage). The other group (n=44) drained when effusion-related symptoms occurred (symptom-guided drainage). In the symptom-guided group, the catheter was also accessed at least fortnightly to check that it was open and whether fluid was still being produced.
• Main results:
  • Breathlessness, the main outcome, did not differ significantly over the first 60 days. The geometric mean score was 13.1 mm (95% CI 9.8 to 17.4) with daily drainage and 17.3 mm (13.0 to 22.0) with symptom-guided drainage. The ratio of geometric means was 1.32 (95% CI 0.88 to 1.97), p=0.18.
  • Spontaneous pleurodesis was more frequent with daily drainage. In the first 60 days, it occurred in 16 (37.2%) of 43 daily-drainage patients and 5 (11.4%) of 44 symptom-guided patients (p=0.0049). After 6 months, the figures were 19 (44.2%) and 7 (15.9%) (p=0.004).
  • In the competing-risk model, daily drainage was associated with a higher likelihood of spontaneous pleurodesis than symptom-guided drainage: hazard ratio 3.287 (95% CI 1.396 to 7.740), p=0.0065.
  • EQ-5D-5L quality-of-life index values were better in the daily-drainage group: estimated mean 0.713 (95% CI 0.647 to 0.779) versus 0.601 (0.536 to 0.667) in the symptom-guided group. The difference was 0.112 (95% CI 0.0198 to 0.204), p=0.0174.
  • On the separate visual analogue quality-of-life scale, the difference between the groups was not statistically significant: ratio of geometric means 1.220 (95% CI 0.871 to 1.709), p=0.25.
  • Mean pain score over 60 days was 10.74 mm (SD 12.80) in the daily-drainage group and 16.31 mm (SD 16.58) in the symptom-guided group. The difference was not significant: ratio of geometric means 1.28 (95% CI 0.76 to 2.18), p=0.35.
  • By 6 months, 18 (41.9%) patients in the daily-drainage group and 19 (43.2%) in the symptom-guided group had died (p=0.90).
  • Serious adverse events occurred in 11 (25.6%) of 43 daily-drainage patients and 12 (27.3%) of 44 symptom-guided patients. There were 11 episodes of pleural infection in nine patients: five episodes in the daily group and six in the symptom-guided group.
  • The authors reported that results did not differ between patients with mesothelioma and those with other cancers.
• The authors' conclusion: The authors concluded that both daily and symptom-guided drainage were adequate for controlling breathlessness. They also concluded that daily drainage enhances spontaneous pleurodesis and might improve quality of life without drawbacks in pain, infection rates or survival.
• Limitations the authors state:
  • The primary endpoint was set at 60 days to reflect the short median survival of patients with effusions from lung cancer.
  • The definition of spontaneous pleurodesis describes fluid stopping. This may reflect treatment or the natural course of the disease rather than true fusion of the pleural layers.
  • Consumable and carer costs of daily drainage vary substantially around the world.
  • Because the study was open label, the patient-reported measures could be biased.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Indwelling Pleural Catheter, Talc, Pleurodesis, Mesothelioma, Performance Status, Trapped Lung, Clinical Trial.

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)
• Indwelling pleural catheter versus talc pleurodesis for malignant pleural effusion: a meta-analysis — M. Yeung, E.W. Loh, et al. (2020)
• Interventional therapies for malignant pleural effusions: the present and the future — R. Thomas, R. Francis, et al. (2014)
• Predictors of clinical use of pleurodesis and/or indwelling pleural catheter therapy for malignant pleural effusion — E.T.H. Fysh, S. Bielsa, et al. (2015)
• 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)
• Intrapleural Fibrinolysis for the Treatment of Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter Observational Study — R. Thomas, F. Piccolo, et al. (2015)

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