This feasibility study has shown that randomising patients with pleural infection to therapeutic thoracentesis or chest tube insertion is, at least in part, feasible. Over 90% of eligible patients offered entry into the trial accepted and were randomised. Additionally, the trial design and processes were acceptable to participants. The intervention has been shown to be safe in previous case series and there were no serious adverse events related to the trial, although absolute numbers were small. Whilst, the trial did not reach its desired recruitment target, the impact of the COVID-19 pandemic makes interpretation of this difficult. From the patients recruited there was a suggestion that hospital length of stay was reduced in the intervention group, a finding that should be explored in a full-scale trial. However, modifications to the intervention and trial procedures are needed before a full-scale trial is undertaken.
This is the first randomised trial comparing TT to the standard of care, chest tube insertion, in pleural infection. A literature review revealed several case series documenting its safe use in European centres (15). Storm et al. published a retrospective study comparing the outcomes of 94 patients with pleural infection (16). Over a 5-year period (1984 to 1989), 51 patients were treated with TT in a medical ward and retrospectively compared to 43 patients treated with chest tube who were admitted to a surgical ward. Although the hospital stay was longer than more recent studies (potentially due to more serious infection at baseline and/or differing medical practices), it was considerably shorter in the TT group (2.3 versus 5 weeks). A more recent case series from France retrospectively analysed patients with pleural infection who had been managed with TT over a 9-year period (2001–2010) (17). The median number of TTs required per patient was 3 (IQR 2–5) with a median hospital length of stay of 21 days. The strategy failed in 15/79 (19%) with 12 patients needing a chest tube inserted and 3 who required thoracic surgery. Importantly, TT complication rates were low despite ultrasound guidance only being used in 53% of the patients. This case series has recently been updated for the period 2011 to 2018 (18). There is no comment on patient tolerability of the approach and complications are similar to those reported in chest drain literature.
The only prospective study of TT in pleural infection was carried out in a paediatric population with ‘severe empyema’(19) between 1992 and 1999. Shoseyov and colleagues performed a non-randomised study comparing TT to chest tube, by virtue of differing practices between three regional hospitals. TT was carried out on alternate days until clinical or radiographic resolution which took on average 2.4 aspirations per patient (range 1 to 4). They found no significant difference between groups in terms of length of stay (24 days in the chest tube group versus 22 days in the TT group), duration of fever, length of antibiotic therapy, amount fluid drained, or need for thoracic surgery. Given the non-randomised nature of these studies it is impossible to directly compare the two treatment methods, but it does demonstrate that TT was safe, with a suggestion of a reduction in hospital stay.
The ACTion trial was set up to assess the feasibility of a full-scale trial of TT versus chest tube for pleural infection. Although the trial met its pre-specified criteria for feasibility, there are other elements to consider when, or if, a full-scale trial is planned. The ACTion trial shows that the concept of the intervention and other trial protocols (questionnaires, follow-ups, blood tests) are acceptable to patients hospitalised with pleural infection. 91% of patients approached accepted randomisation into the trial and there were no withdrawals post-randomisation. Data completeness was high. However, the slow recruitment is a concern for designing a full-scale trial on the intervention, even in the context of COVID-19, and we would suggest adaptions to the protocol to improve recruitment.
A considerable number of patients were excluded from participating in the trial due to lacking capacity at the time of enrolment. This is likely to be an issue for a full-scale trial and there should be a consideration as to whether deferred or personal consultee consent would be appropriate. Patients without capacity secondary to delirium or dementia are a population who are likely to suffer adverse events from chest tube insertion and therefore might benefit most from this trial.
Patient acceptability of randomisation has been demonstrated but acceptability to physicians and other healthcare professionals remains uncertain. Six potentially eligible patients were not offered randomisation on the basis of “being too unwell” without meeting the exclusion criterion of “signs of ongoing sepsis requiring support beyond basis fluid resuscitation”. Given that this trial was run in a unit with experience running interventional pleural studies it can be extrapolated that physician withdrawal would be greater at other hospital sites in a multicentre study. There is no evidence that TT is an inadequate method of source control compared to chest tube. It is crucial that the physicians carrying out the full-scale trial have equipoise and are comfortable with the intervention.
This feasibility trial has weaknesses that affect the generalisability of its findings. Firstly, just 10 patients were recruited. Had the trial met its pre-specified target of 30 patients the additional data generated would have increased confidence in the feasibility of a full-scale trial and might have raised further issues that could be addressed for future studies. The drop in community transmitted bacterial infections, especially pneumococcal, and possible change in healthcare-seeking behaviour caused a significant drop in pleural infection incidence during the trial recruitment period (20). Secondly, as a single centre trial, issues might have been missed that might have been realised in a multicentre study. However, the presentation and diagnosis of pleural infection does not differ significantly by centre, and the interventions (chest tube and therapeutic thoracentesis) are basic procedural skills for acute medical and respiratory physicians.