Antiseptic Pleural Irrigation for Patients With Pleural Infection
Phase: PHASE1
Conditions: Pleural Infection
Sponsor: Alexandria University

 
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The Pleural Infection Cohort Study (PICS) – study protocol  
(version 2.0_10.02.2021) 
 
1.0 Background 
Pleural infection is a condition that requires hospitalization for management and is associated 
with significant in-hospital morbidity and mortality[1]. Predictors of poor outcome include 
advancing age, poor nutrition, hospital-acquired infection and impaired renal function.[2] 
Medical management is centred on appropriate antibiotic treatment and fluid drainage 
usually by the means of an intercostal tube. Up to 30% of patients fail medical treatment and 
referred for surgery.[3]  A recent systematic review of adults patient with pleural infection has 
shown that the demographics of patients with pleural infection are different in patients from 
high-income vs lower income countries; the latter being of younger age and lower 
comorbidity burden.[4] However, the results of the review did not show significant differences 
in patient outcomes. The same systematic review pointed to the need for more data from 
patients residing in lower income countries given that the majority of data is contributed by 
studies from higher income countries.[4] 
This study aims to prospectively investigate the incidence of pleural infection in a large 
tertiary centre gathering demographic and clinical data about patients recruited. In addition, 
the study will examine the different treatment offered and how this related to in-hospital 
outcomes (length of hospital stay, rate of referral to surgery and mortality). 
2.0 Methods 
PICS STUDY 
2.1.1Setting 
The Pleural Infection Cohort Study (PICS) will aim to recruit consecutive patients admitted to 
Alexandria University Hospitals with pleural infection during a one-year period from the 
starting date of the study. 
2.1.2 Design 
The study will be designed as a modified trial within cohort (TwiC) study.[5] PICS will primarily 
aim to recruit patients prospectively to gather clinical and demographic data on patients 
admitted with pleural infection in addition to clinical data on tests performed and treatments 
received as part of the standard care. The in-patient outcomes will be recorded at the time of 
discharge data  or death, whichever is earlier. Within the TWIC design, PICS will be a platform 
for recruiting patients to interventional trials for eligible patients within the cohort (see 
‘consenting’ section) 
2.1.3 Eligibility 
All adult patients admitted with pleural infection who are willing to sign an informed consent 
will be recruited. Pleural infection will be defined by the presence of one of the following: a) 

 
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the presence of pus in the pleural space; b) positive pleural fluid gram stain or culture; or c) 
pleural fluid pH < 7.2 or pleural fluid glucose < 40 mg/dL in the setting of acute respiratory 
infection. 
2.1.4 Consenting and co-enrollment 
In the TwiC design patients are consented to take part in the cohort study with the possibility 
of being randomized in the future into trials without being specifically told if a given eligible 
participant is randomized into a control arm of a trial[5]. 
The consenting process for PICS will involve obtaining consent for the core observational part 
of the study. There will be a separate clause asking for permission to enroll a participant into 
an interventional trial if the participant meets the eligibility criteria. Participants will have the 
opportunity to accept taking part in PICS and reject taking part in interventional trials. The 
consent form will be modified to include clauses for any new trial anchored to the PICS 
platform. Participants will be given clear written information about PICS and any additional 
trials and will be given enough time consider taking part. 
All consenting eligible participants for an interventional trial will be informed in case they are 
randomized to a given trial regardless of the arm they are randomized to. In all cases, a single 
participant will not be enrolled into more than one interventional trial at the same time. 
2.1.5 Study assessments 
PICS is a strictly observational study and all data gathered will be related to the patient’s 
clinical care. The following data will be collected: 
- 
Average age and gender proportion of patients admitted (from screening log) 
- 
Comorbidities 
- 
RAPID score 
- 
Baseline blood tests and follow up inpatient tests (minimum urea and electrolytes, full 
blood count, C-reactive protein, and serum albumin) 
- 
Pleural fluid results 
- 
Microbiological results (pleural fluid and blood) 
- 
Ultrasound findings 
- 
CT findings if available 
- 
Baseline and follow up CXRs 
- 
Treatments received for pleural infection 
- 
Length of hospital stay (LOS) 
- 
Outcome at discharge (medical, surgical, dead) 
Medical treatment will include: thoracentesis, chest drain, fibrinolytic, medical thoracoscopy 
2.1.6 Outcomes 
- 
Examining the incidence of pleural infection admissions locally, the demographics of 
this cohort and range of medical treatments offered. 
- 
Correlating inpatient outcomes with baseline clinical, biochemical, microbiological 
and radiological parameters 

 
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- 
Percent of eligible patients randomized to interventional trials 
 
‘Antiseptic irrigation for patients with pleural infection’ sub-study 
2.2.1 Rationale and design 
The antiseptic povidone-iodine can safely be instilled into the pleural for the purpose of 
pleurodesis[6]. Pleural irrigation with  antiseptics is used in adults with open drainage for 
chronic empyema[7] and has been described in the acute management of paediatric pleural 
infection[8]. 
This sub-study will investigate the safety and usefulness of povione-iodine pleural irrigation 
in 15 eligible patients recruited to PICS. A matched control group will be used and will be 
composed of 15 patients previously recruited to PICS without receiving povione-iodine pleural 
irrigation. 
2.2.2 Additional eligibility criteria 
- Inclusion criteria: 
- Unilocular pleural collection 
- Exclusion criteria: 
- Known or suspected thyroid disease 
- Allergy to iodine 
- Persistent large collection on follow up imaging 24-48 of post tube insertion that is 
deemed to require another drainage procedure  
2.2.3 Specific assessments 
- Two applications of 100-250 ml solution of 2% povidone-iodine will be irrigated into the 
pleural space of eligible patients 12 hours apart. The tube will be clamped for 15 minutes after 
irrigation and the patient will be asked to change position frequently during this period. The 
first dose will be applied 24-72 hours after tube insertion. 
2.2.4 Outcomes 
- Safety: incidence of adverse events (new chest pain, fever, dyspnoea or desaturtion) within 
24 hours from the first irrigation 
- Efficacy 
- Time to defervescence 
- Time to chest tube removal 
- Length of hospital stay 
- Need for additional aspiration/tubes 

 
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_ Failure of medical treatment  
 
3.0 Data management 
A screening log will be kept electronically on a spreadsheet that is password protected on a 
secure computer. This log will have the name and demographics of potential participants 
approached for the study. Separate study numbers for PICS and the interventional trial(s) will 
be assigned and in case of non-enrolment to either, reasons will be recorded. 
 
Data will be collected directly into paper case report forms that will bear the study number 
of the participants but no other identifiable information. No data sources (e.g. lab results, 
etc.) will be stored within the trial files to maintain confidentiality of patients’ medical data. 
4.0 Statistics 
Continuous variables will be compared between the study arms using t-test or Mann Whitney 
test according to the normality of the study data. Categorical variables (including primary 
outcome measure) will be compared using the Chi squared test or Fisher exact test as 
appropriate. 
 
 
 

 
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5.0 References 
1.  Davies HE, Davies RJO, Davies CWH, on behalf of the BTS Pleural Disease Guideline 
Group. Management of pleural infection in adults: British Thoracic Society pleural 
disease guideline 2010. Thorax 2010;65(Suppl 2):ii41–53.  
2.  Corcoran JP, Psallidas I, Gerry S, Piccolo F, Koegelenberg CF, Saba T, et al. Prospective 
validation of the RAPID clinical risk prediction score in adult patients with pleural 
infection: the PILOT study. Eur Respir J 2020; 
3.  Maskell NA, Davies CWH, Nunn AJ, Hedley EL, Gleeson FV, Miller R, et al. U.K. Controlled 
Trial of Intrapleural Streptokinase for Pleural Infection. New England Journal of 
Medicine 2005;352(9):865–74.  
4.  Cargill TN, Hassan M, Corcoran JP, Harriss E, Asciak R, Mercer RM, et al. A systematic 
review of comorbidities and outcomes of adult patients with pleural infection. Eur 
Respir J 2019; 
5.  Kim SY, Flory J, Relton C. Ethics and practice of Trials within Cohorts: An emerging 
pragmatic trial design. Clinical Trials 2018;15(1):9–16.  
6.  Agarwal R, Khan A, Aggarwal AN, Gupta D. Efficacy & safety of iodopovidone 
pleurodesis: a systematic review & meta-analysis. Indian J Med Res 2012;135:297–304.  
7.  Light RW. Parapneumonic effusions and empyema. Proc Am Thorac Soc 2006;3(1):75–
80.  
8.  Togo S, Ouattara MA, Sangaré I, Saye J, Touré CAS, Maiga IB, et al. Management for 
Pediatric Pleural Empyema in Resource-Poor Country: Is Chest Tube Drainage with 
Antiseptic Lavage-Irrigation Better than Tube Thoracostomy Alone? SS 2015;06(12):541–
8.