ISC-TEAM (AMPLE-5) (ACTRN12624000038594)

Malignant pleural effusion (MPE) and mesothelioma are aggressive cancers with poor patient outcomes. High symptom burden of weight loss, fatigue, breathlessness, distress, and anxiety leaves many patients unable to participate in desired physical activities of daily life.  Freedom from symptoms and maintaining daily activities are the key wishes of patients and carers.

Our pleural research program is the first to incorporate dietetics, exercise, and psychology focused research in MPE. Our research has shown that functional impairment, nutritional impairment, psychological distress, and physical inactivity are common and associated with poor outcomes in MPE. Our preliminary data shows that we can improve some of these health outcomes with individual interventions (like exercise training). However, for the best outcome, accessible services aimed at  prevention and management of malnutrition, care of psychological well-being and targeted exercise prescription are required.

The proposed ISC-TEAM trial will randomise 100 patients to receive standard clinical care or integrative supportive care through a multidisciplinary program of dietetics, exercise physiology, and psychology over 12-weeks. 

ISC-TEAM will determine: 

1. if the program improves daily physical activity, measured by steps walked; 

2. if the program improves quality of life, malnutrition risk, psychopathology, and symptoms; and

3. program acceptability and compliance.

The ISC-TEAM  (Integrative Supportive Care Trial to Enhance physical Activity in Malignant pleural effusion) trial will evaluate the effects of a multidisciplinary  supportive care program aimed at improving patients ability to engage in daily physical activities.  We will also evaluate the effects on quality of life, malnutrition risk and psychopathology.  This trial provides, for the first time, the structure and feasibility of a multidisciplinary team model addressing consumer-driven priorities of care for patients with MPE.

AMPLE-4 (ACTRN12623000253606)

Malignant Pleural Effusion (MPE) can complicate most cancers and commonly causes disabling breathlessness and impairs quality of life (QoL). Therefore, the goal of management is to provide effective control of the symptoms with minimal interventions.

Indwelling pleural catheter (IPC) is an ambulatory drainage device for MPE. Randomised studies have proven that IPC is significantly superior to talc slurry pleurodesis in reducing need for invasive pleural interventions and hospital stays whilst providing equivalent benefits in QoL and breathlessness.

IPC-related infections remain a concern for clinicians, particularly in patients eligible for chemotherapy. The incidences of IPC-related infections (of the pleural fluid, catheter tract and skin) vary among series, and their management is heterogenous.¹ IPC-related infections often require hospitalisation and delay oncological treatments. Effective strategies to prevent IPC-related infection will significantly enhance IPC use worldwide.

Care of IPC shares significant similarities with that of peritoneal dialysis (PD) catheters, and infection (especially PD peritonitis) is likewise a major burden for PD programs. Topical antibiotics prophylaxis has recently been shown in several trials to significantly reduce PD catheter-related infections, informing clinical care/guidelines.      

The Australasian Malignant PLeural Effusion (AMPLE) trial-4 is a multicentre RCT that will evaluate the use of regular prophylactic topical mupirocin (vs no antibiotics) to reduce catheter-related infections in patients fitted with an IPC for malignant fluid drainage. Mupirocin is a topical antibiotic used worldwide for 25 years with a strong safety record. Primary outcome is the proportion of patients who developed a catheter-related (pleural, tract or skin) infection from catheter insertion until death (or 6-month follow up). Secondary outcomes include infection rates adjusted for days of catheter in situ, infection-related hospitalisation (episodes and days), treatment acceptability for patients, complications and survival.  

ADAPT-3

Our team showed that tPA dose de-escalation from 10mg (largest open label study of tPA/DNase) to 5mg (ADAPT-1) and 2.5mg (ADAPT-2) maintained treatment efficacy in pleural infection. ADAPT-3 aims to evaluate the safety and efficacy of a starting dosage regimen of 1mg tPA (with 5mg DNase) administered intrapleurally twice daily for pleural infection. The results from this study will inform clinicians on the lowest effective dose of tPA or form the basis of future studies to investigate an even lower dose of tPA for the treatment of pleural infection.

PLEASE-3 (ACTRN12622000465752)

Pleural effusions (excess fluid accumulation between the lung and chest wall) affect 60,000 Australians every year and can arise from a wide range of causes including cancer, heart and liver failure. Pleural effusions often cause disabling breathlessness. Drainage of the fluid (usually requires inserting tubes between the ribs) can relieve symptoms, but the benefits vary among patients. The mechanism by which pleural effusion causes breathlessness remains unclear. A reliable method of identifying the patients likely to respond to drainage may help reduce unnecessary, painful procedures and their associated complications and healthcare costs.

Bendopnoea (breathlessness on bending forward) is a common clinical complaint in patients with pleural effusion but has not been previously studied.  Our pilot data found that bendopnoea was significantly associated with the presence of pleural effusion.  

The PLEASE-3 study will aim to:

1. confirm that bendopnoea is significantly more common in patients with pleural effusion, and can predict improvement in breathlessness after fluid drainage; and
2. describe associations in respiratory physiological tests and ultrasonographic changes of the diaphragm associated with bendopnoea before and after pleural fluid drainage.

This study will evaluate the value of bendopnoea as a screening test for effusion-related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore the physiological mechanisms underlying bendopnoea.

AMPLE-3 (ACTRN12618001303257)

The Australian Malignant PLeural Effusion (AMPLE) trial-3 is a multi-centre, open-labelled, randomised controlled (trial entry) study. One hundred and sixty patients with malignant pleural effusions (MPE), who are suitable for surgical pleurodesis and have a predicted survival of greater than 6 months, will be randomised 1:1 to either video assisted thoroscoscopic surgery (VATs) or indwelling pleural catheter (IPC) insertion with talc pleurodesis, if appropriate. MPE is defined as either histocytologically proven pleural malignancy or an exudative effusion with no other cause in a patient with known primary extra-pleural malignancy. Minimisation for i) cancer type (mesothelioma vs non-mesothelioma); ii) previous pleurodesis (vs not); iii) trapped lung, if known (vs not) will be performed. The nature of the intervention means that investigators and patients cannot be blinded to the treatment arms. 

Primary endpoint: The primary outcome is the percentage of patients in each group requiring a repeat invasive pleural intervention for symptomatic recurrence of the effusion within 12 months or until death, if sooner. Pleural intervention is defined as an ipsilateral surgical procedure, chest drain insertion or thoracentesis with therapeutic intent. Clinically indicated diagnostic sampling procedures (e.g. to exclude infection) are excluded.

AIR (ACTRN12615000337572)

Abnormality of the pleura is a common clinical problem. It is usually seen in  the  setting of cancer that may arise from within the pleura (such as mesothelioma) or spread to the  pleura from other sites, most commonly from the lung or breast. More than 8000 Australians suffer from a malignant pleural effusion secondary to cancer of the pleura every year causing disabling breathlessness.

Computed tomography (CT) is the standard imaging modality for detection of pleural abnormalities such as nodules or pleural thickening in the setting of a malignant pleural effusion (MPE), and usually guides diagnostic investigations, such as pleural biopsy. CT however, is often unable to detect small pleural nodules (~1cm) even when these nodules are visible on direct inspection, e.g. during thoracoscopy. As a consequence, many patients with suspected malignant pleural disease are forced to undergo surgery such as thoracoscopy to obtain histology for a diagnosis. Surgery has its attendant morbidity and many patients are not suitable to undergo surgical procedures due to age or underlying comorbidities leading to delayed diagnosis and treatment.

Objectives: We hypothesize that a CT scan is unable to easily detect pleural nodules because the pleural abnormality and surrounding lung and/or pleural effusion have similar CT density. We hypothesize that artificially creating an air-pleura interface will reveal small pleural nodules (~1cm) and allow significantly better detection of previously undetectable pleural abnormalities nodules by CT scan.