Pleural infection Respiratory
Conditions
Interventions
Randomisation to one of two arms in a 1:1 ratio, utilising sealed envelope randomisation software:
1. Intrapleural Enzyme Therapy (or IET) – this involves giving six doses of IET therapy (DNase and al
follow-up activity for both arms will follow standard of care.
Sponsors
Oxford Respiratory Trials Unit
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: All patients will initially be treated with chest drain insertion for up to 24 hours, and only those with residual pleural collections will be randomised (MIST-3 demonstrated that with an identical recruitment strategy, 15% of patients required no further treatment), hence this will enrich the population for those who stand to benefit most from intervention. Pleural infection will be diagnosed on BTS guideline criteria. 1. Aged 18 years or above. 2. Clinical presentation compatible with pleural infection plus, pleural fluid requiring drainage which is: 2.1. Purulent OR 2.2. Culture positive OR 2.3. Acidic (pH 1000, glucose 6) will be excluded. Patients with significant comorbidities (e.g., renal or cardiac failure) will remain eligible. Participants randomised to surgery who are later deemed unfit will still be analysed in the intention-to-treat population, consistent with the previous feasibility trial.
Exclusion criteria
Exclusion criteria: 1. Has previously received an intrapleural fibrinolytic and/or DNase for this episode of pleural infection 2. Has previously received large volume saline flushes akin to irrigation for this episode of pleural infection* 3. Has a known sensitivity to tPA or DNase. 4. Has had a previous pneumonectomy on the side of the infection. 5. Coincidental major bleed within the last 7 days. 6. Clinically significant renal or hepatic impairment in the view of the recruiting clinician e.g. CKD 5 on dialysis or advanced cirrhosis. 7. Participant with life expectancy of less than 3 months due to other disease (for example, known malignancy with poor prognosis). 8. Female participant of childbearing age who is pregnant, lactating or planning pregnancy during the trial. 9. Scheduled elective surgery (i.e. not for this episode of pleural infection) or other procedures requiring general anaesthesia within 30 days of prospective enrolment. 10. Significant irreversible coagulopathy that in the local investigator's opinion would prevent the participant from safely receiving IET. 11. Participation in another interventional clinical trial for pleural infection. * Standard intrapleural saline flush regimens to maintain tube patency (e.g. 20 ml qds / 30 ml tds) are permitted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment failure of initial randomised intervention (either VATS or IET) over 90 days post randomisation. Treatment failure is any of the following: 1. Any further pleural intervention required after initial intended treatment: 1.1. Further chest tube insertion 1.2. Surgical intervention (further VATS debridement, thoracotomy, thoracostomy) 1.3. Any additional intrapleural therapy including IET (any dose in the VATS group, and further doses beyond 6 doses in the IET group) and saline irrigation 2. Death (all cause) 3. Re-admission post discharge for pleural infection related events 4. Re-escalation of antibiotics from oral to intravenous or re-initiation of antibiotic treatment once initial treatment course completed | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Quality of life measured using EQ-5D-5L +bolt ons at baseline, 2 weeks and 90 days 2. Length of hospital stay - randomisation to 90 days – including re-admission in relation to the initial in-patient episode at 90 days 3. Total days of antibiotics at 90 days, measured using patients’ medical records 4. Days to intervention (IET/surgical treatment) from randomisation, measured using patients’ medical records 5. Complications measured using the Comprehensive Complication Index (CCI) at 30 days 6. Days at Home up to 30 days after randomisation (DAH-30) measured using patients’ medical records 7. Adverse events(AEs) by average number of AEs and percentage of participants with at least one AE (assessed from intervention) at 90 days 8. Death (all cause) at 12 months measured using patients’ medical records 9. Pain measured using validated 100 mm Visual Analogue Scale (VAS) at baseline, Day 1 post trial intervention, discharge, weekly post randomisation from 2 weeks and 90 days 10. Spirometry (FEV1% predicted) at 2 weeks post randomisation and 90 days 11. Objective measurement of pleural shadowing on chest x-ray (CXR) or CT at baseline, 2 weeks and 90 days 12. Cost by incremental cost per quality-adjusted life year (QALY) gained at baseline to 90 days, measured using patients’ medical records | — |
Countries
England, United Kingdom
Contacts
Public ContactEllie Daly
Outcome results
None listed