Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial

Abstract

Importance: Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis.

Objective: To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion.

Design, setting, and participants: This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n = 146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included.

Interventions: Participants were randomized (1:1) to indwelling pleural catheter (n = 74) or talc pleurodesis (n = 72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia).

Main outcomes and measures: The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events.

Results: Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P = .03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P < .001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events).

Conclusions and relevance: Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion.

Trial registration: anzctr.org.au Identifier: ACTRN12611000567921.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Y. C. G. Lee reported receiving grants, nonfinancial support, personal fees, and/or other funding from the Cancer Council of Western Australia, Dust Diseases Board of New South Wales, Sir Charles Gairdner Research Advisory Committee, National Health & Medical Research Council Australia, Rocket Ltd (unrestricted educational grant), CareFusion/BD (advisory board), and Sequana Medical (advisory board). Dr Kosky reported serving on the advisory board of Teva Pharmaceutical Australia and receiving travel grants and speakers’ fees from UCB UK. Drs Thomas, Kwan, Yap, Lam, Garske, Shrestha, and Y. C. G. Lee are investigators of the AMPLE-2 trial for which Rocket Ltd provided the drainage supplies without charge. No other disclosures were reported.

Figures

Figure 1.. Participant Enrollment, Treatment, Follow-up, and Analysis

IPC indicates indwelling pleural catheter. aA total of 25 patients were screened but found ineligible for the following reasons: expected survival less than 3 months (n = 5), inability to care for IPC for logistic reasons (remote location) (n = 4), previous pleurodesis (n = 6), nonmalignant etiology (n = 7), and asymptomatic from effusion (n = 3).

Figure 2.. Time in Hospital Until Death or 12-Month Follow-up

The horizontal lines in boxes indicate medians; lower and upper edges of boxes, interquartile ranges; and whiskers above and below the box, 90th and 10th percentiles, respectively. Left panel: P = .03; right panel: P = .01.

Figure 3.. Comparison of Patient-Reported Outcomes Between Those Randomized to Receive an Indwelling Pleural Catheter (IPC) and Those Randomized to Receive Talc Pleurodesis

Points are estimated means from linear mixed models with error bars representing 95% CIs. Time 0 denotes the time of treatment intervention; sample size differs owing to missing data. A, Breathlessness score was measured with a visual analog scale, with a 100-mm line anchored with “no breathlessness” at 100 mm and “worst imaginable breathlessness” at 0 mm. B, Quality-of-life score was measured with a visual analog scale, with a 100-mm line anchored with “best quality of life” at 100 mm and “worst quality of life” at 0 mm. C, The EuroQol 5 Dimensions quality-of-life score consisted of 5 domains: mobility, self-care, usual activities, discomfort/pain, and anxiety/depression. Each domain was graded by the patient from 0 (worst imaginable) to 10 (best imaginable) and the total score out of a maximum 50 points was presented.