Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

Importance: Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective: To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions: Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures: The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results: Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance: Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

A Pilot Feasibility Study in Establishing the Role of Ultrasound-Guided Pleural Biopsies in Pleural Infection (The AUDIO Study).

BACKGROUND: Pleural infection is a common complication of pneumonia associated with high mortality and poor clinical outcome. Treatment of pleural infection relies on the use of broad-spectrum antibiotics because reliable pathogen identification occurs infrequently. We performed a feasibility interventional clinical study assessing the safety and significance of ultrasound (US)-guided pleural biopsy culture to increase microbiological yield. In an exploratory investigation, the 16S ribosomal RNA technique was applied to assess its utility on increasing speed and accuracy vs standard microbiological diagnosis. METHODS: Twenty patients with clinically established pleural infection were recruited. Participants underwent a detailed US scan and US-guided pleural biopsies before chest drain insertion, alongside standard clinical management. Pleural biopsies and routine clinical samples (pleural fluid and blood) were submitted for microbiological analysis. RESULTS: US-guided pleural biopsies were safe with no adverse events. US-guided pleural biopsies increased microbiological yield by 25% in addition to pleural fluid and blood samples. The technique provided a substantially higher microbiological yield compared with pleural fluid and blood culture samples (45% compared with 20% and 10%, respectively). The 16S ribosomal RNA technique was successfully applied to pleural biopsy samples, demonstrating high sensitivity (93%) and specificity (89.5%). CONCLUSIONS: Our findings demonstrate the safety of US-guided pleural biopsies in patients with pleural infection and a substantial increase in microbiological diagnosis, suggesting potential niche of infection in this disease. Quantitative polymerase chain reaction primer assessment of pleural fluid and biopsy appears to have excellent sensitivity and specificity.

Efficacy of sonographic and biological pleurodesis indicators of malignant pleural effusion (SIMPLE): protocol of a randomised controlled trial.

INTRODUCTION: Malignant pleural effusion (MPE) is common and currently in UK there are an estimated 50 000 new cases of MPE per year. Talc pleurodesis remains one of the most popular methods for fluid control. The value of thoracic ultrasound (TUS) imaging, before and after pleurodesis, in improving the quality and efficacy of care for patients with MPE remains unknown. Additionally, biomarkers of successful pleurodesis including measurement of pleural fluid proteins have not been validated in prospective studies.The SIMPLE trial is an appropriately powered, multicentre, randomised controlled trial designed to assess 'by the patient bedside' use of TUS imaging and pleural fluid analysis in improving management of MPE. METHODS AND ANALYSIS: 262 participants with a confirmed MPE requiring intervention will be recruited from hospitals in UK and The Netherlands. Participants will be randomised (1:1) to undergo either chest drain insertion followed by instillation of sterile talc, or medical thoracoscopy and simultaneous poudrage. The allocated procedure will be done while the patient is hospitalised, and within 3 days of randomisation. Following hospital discharge, participants will be followed up at 1, 3 and 12 months. The primary outcome measure is the length of hospital stay during initial hospitalisation. ETHICS AND DISSEMINATION: The trial has received ethical approval from the South Central-Oxford C Research Ethics Committee (Reference number 15/SC/0600). The Trial Steering Committee includes an independent chair and members, and a patient representative. The trial results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN: 16441661.

Evaluating the efficacy of thoracoscopy and talc poudrage versus pleurodesis using talc slurry (TAPPS trial): protocol of an open-label randomised controlled trial.

INTRODUCTION: The management of recurrent malignant pleural effusions (MPE) can be challenging. Various options are available, with the most efficacious and widely used being talc pleurodesis. Talc can either be applied via a chest drain in the form of slurry, or at medical thoracoscopy using poudrage. Current evidence regarding which method is most effective is conflicting and often methodologically flawed. The TAPPS trial is a suitably powered, multicentre, open-label, randomised controlled trial designed to compare the pleurodesis success rate of medical thoracoscopy and talc poudrage with chest drain insertion and talc slurry. METHODS AND ANALYSIS: 330 patients with a confirmed MPE requiring intervention will be recruited from UK hospitals. Patients will be randomised (1:1) to undergo either small bore (<14 Fr) Seldinger chest drain insertion followed by instillation of sterile talc (4 g), or to undergo medical thoracoscopy and simultaneous poudrage (4 g). The allocated procedure will be performed as an inpatient within 3 days of randomisation taking place. Following discharge, patients will be followed up at regular intervals for 6 months. The primary outcome measure is pleurodesis failure rates at 3 months. Pleurodesis failure is defined as the need for further pleural intervention for fluid management on the side of the trial intervention. ETHICS AND DISSEMINATION: The trial has received ethical approval from the National Research Ethics Service Committee North West-Preston (12/NW/0467). There is a trial steering committee which includes independent members and a patient and public representative. The trial results will be published in a peer-reviewed journal and presented at international conferences, as well as being disseminated via local and national charities and patient groups. All participants who wish to know the study results will also be contacted directly on their publication. TRIAL REGISTRATION NUMBER: ISRCTN47845793.