Perioperative Respiratory Care and Outcomes for Patients Undergoing High Risk Abdominal Surgery

Study Overview
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Brief Summary
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PENGUIN is a pragmatic multi-center trial investigating the effects of pre-operative mouthwash and perioperative oxygen on the incidences of pneumonia and surgical site infection (SSI) following major abdominal surgery. Patients will be recruited from low and middle income countries and randomly assigned to a trial treatment arms: a) pre-operative chlorhexidine mouthwash and 80-100% FiO2; b) no pre-operative mouthwash and 80-100% fraction of inspired oxygen (FiO2); c) pre-operative chlorhexidine mouthwash and 21- 30% FiO2; or d) no pre-operative mouthwash and 21-30% FiO2.

Detailed Description
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PENGUIN is a pragmatic, blinded (outcome assessor), 2x2 factorial, multi-centre randomised controlled trial, with an internal pilot, to evaluate measures to reduce surgical site infection (SSI) and pneumonia rates in patients undergoing surgery with an abdominal incision. Pneumonia is one of the most serious complications to occur after surgery, accounting for up to one in four of all postoperative deaths. The incidence is greater still in high-risk populations such as those undergoing midline laparotomy where mortality rates are more than 10%. SSIs are clearly important being the most frequent healthcare-associated infection in LMICs, affecting one in three patients undergoing contaminated or dirty surgery (34, 35). SSIs cause pain, discomfort and disability. They increase the time taken to return to work, and healthcare costs The risk of postoperative mortality and complications such as surgical site infection is three times greater in low and middle-income countries (LMICs) than in high-income countries. In order to address surgical need worldwide, it is estimated that provision of a further 312 million operations would be required each year. Patients will be recruited from hospitals in Low and Middle Income Countries (LMICs) who are undergoing elective or emergency mid-line laparotomy. Eligible patients will be randomised at the level of the individual in a 1:1:1:1 ratio between: A. Preoperative chlorhexidine mouthwash and 80-100% FiO2 during surgery B. No preoperative chlorhexidine mouthwash and 80-100% FiO2 during surgery C. Preoperative chlorhexidine mouthwash and 21-30% FiO2 during surgery D. No preoperative chlorhexidine mouthwash and 21-30% FiO2 during surgery The 6 month internal pilot will assess the feasibility of recruitment, compliance with treatment allocation and patient retention and follow-up rates. The main Randomised Control Trial will recruit 12,924 participants.

Official Title
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PErioperative Respiratory Care and Outcomes for patieNts Undergoing hIgh Risk abdomiNal Surgery: A 2x2 Factorial, International Pragmatic Randomised Controlled Trial Across Low and Middle-income Countries

Conditions
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Infection, Pneumonia, Surgical Site Infection, Wound Infection, Surgical Wound Infection, Postoperative Complications, Anesthesia, Communicable Disease, Pathologic Processes, Perioperative Complication, Chlorhexidine, Laparotomy

Intervention / Treatment
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* Drug: Chlorhexidine mouthwash
* Drug: Oxygen
* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults and children aged 10 years or over Elective or emergency abdominal surgery via midline laparotomy with an anticipated abdominal incision of at least 5cm in length Written informed consent of patient (signature or a fingerprint) Exclusion Criteria: Patients undergoing caesarean section Patients with a documented or suspected allergy to chlorhexidine Patient unable to complete postoperative follow-up (not contactable after discharge) Previous enrolment in PENGUIN within the past 30 days American Society of Anesthesiologists (ASA) grade V patients (expected to die with or without surgery)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 100 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mouthwash and liberal oxygen during surgery<br>Pre-surgical mouthwash with 0.2% chlorhexidine gluconate in combination with 80-100% FiO2 during surgery. | Drug: Chlorhexidine mouthwash<br>* 0.2% Chlorhexidine digluconate<br>Drug: Oxygen<br>* Oxygen 80-100%<br>|
| Active Comparator: No mouthwash and liberal oxygen during surgery<br>No pre-surgical mouthwash in combination with 80-100% FiO2 during surgery. | Drug: Oxygen<br>* Oxygen 80-100%<br>|
| Experimental: Mouthwash and restrictive oxygen during surgery<br>Pre-surgical mouthwash with 0.2% chlorhexidine gluconate in combination with 21-30% FiO2 during surgery. | Drug: Chlorhexidine mouthwash<br>* 0.2% Chlorhexidine digluconate<br>Drug: Oxygen<br>* Oxygen 21-30 %<br>|
| Active Comparator: No mouthwash and restrictive oxygen during surgery<br>No pre-surgical mouthwash in combination with 21-30% FiO2 during surgery. | Drug: Oxygen<br>* Oxygen 21-30 %<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with pneumonia using the US Centers for Disease Control (CDC) definition of pneumonia (Mouthwash intervention only) | Pneumonia will be classified using the US Centers for Disease Control (CDC) definition of pneumonia | Within 30 days post-surgery from index operation | 
| Number of participants with surgical site infection (Oxygen therapy intervention only) | The infection must involve the skin, subcutaneous, muscular or fascial layers of the incision AND The patient must have at least one of the following: Purulent drainage from the wound Organisms are detected from a wound swab Wound opened spontaneously or by a clinician AND, fever (>38°C), OR at the surgical wound, the patient has at least one of: pain or tenderness; localised swelling; redness; heat; Diagnosis of SSI by a clinician or radiological imaging | Within 30 days post-surgery from index operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of trial participant moralities (Mouthwash and oxygen therapy intervention comparisons) | Patient mortality status | Within 30 days post-surgery from index operation | 
| Number of participants who received repeat abdominal surgery to treat complications (Oxygen therapy intervention only) | Repeat abdominal surgery to treat complications | Within 30 days post-surgery from index operation | 
| Number of participants who received repeat abdominal surgery (Mouthwash and oxygen therapy interventions) | Repeat abdominal surgery | Within 30 days post-surgery from index operation | 
| Length of hospital stay for index admission (Mouthwash and oxygen therapy interventions) | Length of hospital stay for index admission will be collected and will measure time from surgery to time of discharge. | Within 30-days post surgery from index operation | 
| Number of participants returning to normal activities (Mouthwash and oxygen therapy interventions) | Return to normal activities (e.g. work, school, or family duties) ascertained by trial specific case report forms. | Within 30 days post-surgery from index operation | 
| Number of participants admissions to a critical care unit (Mouthwash and oxygen therapy interventions) | Admission to a critical care unit will be captured on the trial case report forms. | Within 30 days post-surgery from index operation | 
| Health resource usage per patient | Resource use data will be collected as part of the economic evaluation of the different treatment combinations in a sub-group of adult patients at selected centers. Information related to post-operative cost (medicinal products, amenities and personal) will be collected on a health resource usage case report form designed by the trials health economist. | Within 30 days post-surgery from index operation |