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

Muruganandan S 1 , Azzopardi M 2 , Fitzgerald DB 3 , Shrestha R 4 , Kwan BCH 5 , Lam DCL 6 Show all authors , De Chaneet CC 7 , Rashid Ali MRS 8 , Yap E 9 , Tobin CL 10 , Garske LA 11 , Nguyen PT 12 , Stanley C 4 , Popowicz ND 13 , Kosky C 14 , Thomas R 1 , Read CA 15 , Budgeon CA 16 , Feller-Kopman D 17 , Maskell NA 18 , Murray K 16 , Lee YCG 19

Affiliations 

  • 1 Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; Pleural Medicine Unit, Institute for Respiratory Health, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
  • 2 School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Department of Respiratory Medicine, Sunshine Coast University Hospital, Birtinya, QLD, Australia
  • 3 Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; Pleural Medicine Unit, Institute for Respiratory Health, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; School of Medicine, University College Dublin, Dublin, Ireland
  • 4 Department of Respiratory Medicine, Fiona Stanley Hospital, Perth, WA, Australia
  • 5 Department of Respiratory and Sleep Medicine, Sutherland Hospital, Sydney, NSW, Australia
  • 6 Department of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
  • 7 Saint John of God Hospital Bunbury, Bunbury, WA, Australia
  • 8 Department of Respiratory Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia; KPJ Johor Specialist Hospital, Johor Bahru, Malaysia
  • 9 Respiratory Department, Middlemore Hospital, Auckland, New Zealand
  • 10 School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Respiratory Department, Royal Perth Hospital, Perth, WA, Australia
  • 11 Wesley Hospital, Brisbane, QLD, Australia
  • 12 Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
  • 13 Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; School of Allied Health, University of Western Australia, Perth, WA, Australia
  • 14 School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Department of Pulmonary Physiology and General Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
  • 15 Pleural Medicine Unit, Institute for Respiratory Health, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
  • 16 Centre for Applied Statistics and School of Population & Global Health, University of Western Australia, Perth, WA, Australia
  • 17 Division of Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA
  • 18 Academic Respiratory Unit, Bristol Medical School, University of Bristol, Bristol, UK
  • 19 Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; Pleural Medicine Unit, Institute for Respiratory Health, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. Electronic address: gary.lee@uwa.edu.au
Lancet Respir Med, 2018 09;6(9):671-680.
PMID: 30037711 DOI: 10.1016/S2213-2600(18)30288-1

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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