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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pathologic Processes; Pneumonia; Postoperative Complications; Surgical Wound Infection; Surgical Site Infection; Wound Infection; Anesthesia; Infection; Laparotomy; Communicable Disease; Perioperative Complication; Chlorhexidine
• Intervention / Treatment: Drug: Chlorhexidine mouthwash; Drug: Oxygen; Drug: Oxygen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 12942
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Matthew Soden, BSc, PhD; Phone Number: 0121 414 4762; Email: penguin@trials.bham.ac.uk
• Study Contact Backup: Name: Rachel Lillywhite, BA; Phone Number: 0121 414 4762; Email: penguin@trials.bham.ac.uk

Study Locations

• South Africa
  • Cape Town, South Africa, 7925
    • Recruiting
    • Groote Schuur Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Birmingham
• Investigators: Principal Investigator: Rupert Pearse, Royal London Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Disease Attributes; Infections; Communicable Diseases; Wounds and Injuries; Surgical Wound; Postoperative Complications; Surgical Wound Infection; Wound Infection; Pathologic Processes; Anti-Infective Agents, Local; Anti-Infective Agents; Disinfectants; Chlorhexidine
• Other Study ID Numbers: RG_19-223

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared via a process of controlled access
• IPD Sharing Time Frame: 6 months post publication
• IPD Sharing Access Criteria: Formal requests must be submitted to the Data Access Group at Birmingham Clinical Trials Unit
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No