Trial of Antiseptic Irrigation for Pleural Infection

Study Overview
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Brief Summary
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Pleural antiseptic irrigation (PAI) is used in conjunction with open drainage for treating adults with chronic post-thoracotomy empyema. The antiseptic povidone-iodine can safely be instilled into the pleural cavity for the purpose of pleurodesis and has recently been described for pleural irrigation in the acute management of paediatric pleural infection with good outcomes. A recent case report demonstrated the safe use of povidone-iodine pleural irrigation in a patient with complex pleural empyema with successful medical management. In a previous pilot study, antiseptic irrigation led to less referral to surgery and shorter length of hospital stay in comparison to no irrigation. This study aims to investigate the effect of antiseptic pleural irrigation (using povidone iodine) on the inflammatory response in adults patients with pleural infection in comparison to irrigation with normal saline alone. A reduction in the systemic inflammatory response can be inferred to correlate with reduction in the infection burden in the pleural space.

Official Title
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IrRigation of the INfected Pleural Space With antiSEptic Solution (RINSE) - a Proof of Concept Study

Conditions
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Empyema, Pleural

Intervention / Treatment
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* Drug: Povidone-iodine solution
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (18 year-old or more) Pleural infection diagnosed by: the presence of pus in the pleural space, OR any of the following in the setting of acute lower-respiratory tract infection symptoms: pleural fluid PH<7.2 or pleural fluid glucose <40 mg/dL, positive gram stain or culture from pleural fluid Predominantly unilocular pleural collection treated with chest tube drainage Acute response at presentation as evidenced by fever (>37.80C) and/or blood leucocytosis (>11X103/mm3) and/or high serum C-reactive protein, CRP (>50 mg/L) Exclusion Criteria: Known or suspected thyroid disease Allergy to iodine Persistent large collection on follow-up imaging 24-48 post tube insertion that is deemed to require additional interventions (e.g., another drainage procedure, intrapleural fibrinolytic) Evidence or suspicion of broncho-pleural fistula (suspected when there is air-fluid level without previous intervention, or if the participant is coughing large volume of purulent sputum that is physically similar to drained pleural fluid) Tuberculous, post-operative or post-haemothorax pleural infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antiseptic irrigation arm<br>250 ml solution of 2% povidone-iodine (i.e. 50 ml betadine in 200 ml saline) will be attached to the chest tube via a giving set and a 3-way tap and irrigated into the pleural space with gravity. The chest tube will be clamped for 10-20 minutes after irrigation and then will be unclamped and left to drain freely. The first dose will be applied 24-48 hours after tube insertion. This will be repeated every 12 hours for a total of four to six applications. | Drug: Povidone-iodine solution<br>* Pleural irrigation with 2% povidone iodine<br>|
| Active Comparator: Saline irrigation arm<br>250 ml solution of normal saline will be attached to the chest tube via a giving set and a 3-way tap and irrigated into the pleural space with gravity. The chest tube will be clamped for 10-20 minutes after irrigation and then will be unclamped and left to drain freely. The first dose will be applied 24-48 hours after tube insertion. This will be repeated every 12 hours for a total of four to six applications. | Drug: Normal saline<br>* Pleural irrigation with normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in inflammatory markers before and after irrigation | The percentage by which inflammatory marker (CRP and/or procalcitonin) decrease after completing all irrigations in comparison to the pre-irrigation inflammatory markers level | Initial levels to be measured 12 to 48 hours post tube insertion and follow up levels 12 to 24 hours post last dose of irrigation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in days to chest tube removal | The time in days from the first irrigation to the chest tube removal | At the time of chest tube removal (up to 6 weeks) | 
| Total length of hospital stay in days | Duration of hospital stay from admission until a patient is declared medically fit for discharge | At the point of deciding a patient is medically fit for discharge (assessed up to 6 weeks) | 
| Percentage of radiological clearance between baseline and discharge chest X-rays | Percentage of radiological clearance of pleural abnormalities between baseline and discharge chest X-rays using a computer software | baseline and discharge (up to week 6) | 
| Incidence of medical treatment failure | Number of patients who fail medical treatment (referral to surgery, further pleural procedures or death) | At discharge from the hospital or referral to another department (assessed up to week 6) | 
| Incidence of adverse events | Number of patients with different types of adverse events | Adverse events will be recognised if they appear within 6 hours of a given irrigation procedure |