Randomised ambulatory management of primary pneumothorax (RAMPP): Protocol of an open-label, randomised controlled trial

Introduction Pneumothorax is a common clinical problem. Primary spontaneous pneumothorax (PSP) occurs in otherwise fit young patients, but optimal management is not clearly defined and often results in a long hospital stay. Ambulatory treatment options are available, but the existing data on their efficacy are poor. The Randomised Ambulatory Management of Primary Pneumothorax trial is a multicentre, randomised controlled trial comparing ambulatory management with standard care, specifically designed to safely and effectively reduce hospital stay. Methods and analysis 236 patients with PSP will be recruited from UK hospitals. Patients will be randomised 1:1 to treatment to either the 'Intervention' arm (ambulatory device; Rocket Pleural Vent) or the 'Control' arm (aspiration ± standard chest drain insertion). Patients will be followed up for a total of 12 months to assess recurrence rates. The primary outcome is total length of stay in hospital (including readmissions) up to 30 days postrandomisation. The secondary outcomes are pain and breathlessness scores, air leak measurement and radiological evidence (on CT scanning) of emphysema-like changes, compared with short-term and long-term outcomes, respectively, and health economic analysis. Ethics and dissemination The trial has received ethical approval from the National Research Ethics Service Committee South-Central Oxford A (15/SC/0240)

Ambulatory management of secondary spontaneous pneumothorax: a randomised controlled trial

Objective: Secondary spontaneous pneumothorax (SSP) is traditionally managed with an intercostal chest tube attached to an underwater seal. We investigated whether use of a one-way flutter valve shortened length of patients’ stay (LoS). / Methods: This open-label randomised controlled trial enrolled patients presenting with SSP and randomised to either a chest tube and underwater seal (standard care: SC) or ambulatory care (AC) with a flutter valve. The type of flutter valve used depended on whether at randomisation the patient already had a chest tube in place: in those without a chest tube a Pleural Vent (PV) was used; in those with a chest tube in situ, an Atrium Pneumostat (AP) valve was attached. The primary end-point was LoS. / Results: Between March 2017 and March 2020, 41 patients underwent randomisation: 20 to SC and 21 to AC (13=PV, 8=AP). There was no difference in LoS in the first 30 days following treatment intervention: AC (median=6 days, IQR 14.5) and SC (median=6 days, IQR 13.3). In patients treated with PV there was a high rate of early treatment failure (6/13; 46%), compared to patients receiving SC (3/20; 15%) (p=0.11) Patients treated with AP had no (0/8 0%) early treatment failures and a median LoS of 1.5 days (IQR 23.8). / Conclusion: There was no difference in LoS between ambulatory and standard care. Pleural Vents had high rates of treatment failure and should not be used in SSP. Atrium Pneumostats are a safer alternative, with a trend towards lower LOS

Role of thoracic ultrasonography in pleurodesis pathways for malignant pleural effusions (SIMPLE): an open-label, randomised controlled trial

BACKGROUND: Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75-80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. METHODS: The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. FINDINGS: Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2-4]) than in the standard care group (3 days [2-5]; difference 1 day [95% CI 1-1]; p<0·0001). In the per-protocol analysis, thoracic ultrasonography-guided care was non-inferior to standard care in terms of pleurodesis failure at 3 months, which occurred in 27 (29·7%) of 91 patients in the intervention group versus 34 (31·2%) of 109 patients in the standard care group (risk difference -1·5% [95% CI -10·2% to 7·2%]; non-inferiority margin 15%). Mean time to chest tube removal in the intervention group was 2·4 days (SD 2·5) versus 3·1 days (2·0) in the standard care group (mean difference -0·72 days [95% CI -1·22 to -0·21]; p=0·0057). There were no significant between-group differences in all-cause mortality, symptom scores, or quality-of-life scores, except on the EQ-5D visual analogue scale, which was significantly lower in the standard care group at 3 months. Although costs were similar between the groups, thoracic ultrasonography-guided care was cost-effective compared with standard care. INTERPRETATION: Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. FUNDING: Marie Curie Cancer Care Committee

Ambulatory management of primary spontaneous pneumothorax: an open-label, randomised controlled trial

BACKGROUND: Primary spontaneous pneumothorax occurs in otherwise healthy young patients. Optimal management is not defined and often results in prolonged hospitalisation. Data on efficacy of ambulatory options are poor. We aimed to describe the duration of hospitalisation and safety of ambulatory management compared with standard care. METHODS: In this open-label, randomised controlled trial, adults (aged 16-55 years) with symptomatic primary spontaneous pneumothorax were recruited from 24 UK hospitals during a period of 3 years. Patients were randomly assigned (1:1) to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion, or both). The primary outcome was total length of hospital stay including re-admission up to 30 days after randomisation. Patients with available data were included in the primary analysis and all assigned patients were included in the safety analysis. The trial was prospectively registered with the International Standard Randomised Clinical Trials Number, ISRCTN79151659. FINDINGS: Of 776 patients screened between July, 2015, and March, 2019, 236 (30%) were randomly assigned to ambulatory care (n=117) and standard care (n=119). At day 30, the median hospitalisation was significantly shorter in the 114 patients with available data who received ambulatory treatment (0 days [IQR 0-3]) than in the 113 with available data who received standard care (4 days [IQR 0-8]; p<0·0001; median difference 2 days [95% CI 1-3]). 110 (47%) of 236 patients had adverse events, including 64 (55%) of 117 patients in the ambulatory care arm and 46 (39%) of 119 in the standard care arm. All 14 serious adverse events occurred in patients who received ambulatory care, eight (57%) of which were related to the intervention, including an enlarging pneumothorax, asymptomatic pulmonary oedema, and the device malfunctioning, leaking, or dislodging. INTERPRETATION: Ambulatory management of primary spontaneous pneumothorax significantly reduced the duration of hospitalisation including re-admissions in the first 30 days, but at the expense of increased adverse events. This data suggests that primary spontaneous pneumothorax can be managed for outpatients, using ambulatory devices in those who require intervention. FUNDING: UK National Institute for Health Research

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (RAPID - Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) in adults with pleural infection. METHODS: Prospective observational cohort study recruiting patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment, and lung function at 3 months. RESULTS: Mortality data were available in 542 of 546 (99.3%) patients recruited. Overall mortality was 10% (54/542) at 3 months and 19% (102/542) at 12 months. The RAPID risk category predicted mortality at 3 months; low-risk (RAPID score 0-2) mortality 5/222 (2.3%, 95%CI 0.9 to 5.7), medium-risk (RAPID score 3-4) mortality 21/228 (9.2%, 95%CI 6.0 to 13.7), and high-risk (RAPID score 5-7) mortality 27/92 (29.3%, 95%CI 21.0 to 39.2). C-statistics for the score at 3 and 12 months were 0.78 (95%CI 0.71 to 0.83) and 0.77 (95%CI 0.72 to 0.82) respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (RAPID - Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) in adults with pleural infection. METHODS: Prospective observational cohort study recruiting patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment, and lung function at 3 months. RESULTS: Mortality data were available in 542 of 546 (99.3%) patients recruited. Overall mortality was 10% (54/542) at 3 months and 19% (102/542) at 12 months. The RAPID risk category predicted mortality at 3 months; low-risk (RAPID score 0-2) mortality 5/222 (2.3%, 95%CI 0.9 to 5.7), medium-risk (RAPID score 3-4) mortality 21/228 (9.2%, 95%CI 6.0 to 13.7), and high-risk (RAPID score 5-7) mortality 27/92 (29.3%, 95%CI 21.0 to 39.2). C-statistics for the score at 3 and 12 months were 0.78 (95%CI 0.71 to 0.83) and 0.77 (95%CI 0.72 to 0.82) respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population