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

Sponsor

University of Birmingham (Other)

Overall Status

Recruiting

CT.gov ID

NCT04256798

Collaborator

(none)

12,942

Enrollment

Location

Arms

42.6

Anticipated Duration (Months)

304

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infection Pneumonia Surgical Site Infection Wound Infection Surgical Wound Infection Postoperative Complications Anesthesia Communicable Disease Pathologic Processes Perioperative Complication Chlorhexidine Laparotomy	Drug: Chlorhexidine mouthwash Drug: Oxygen Drug: Oxygen	Phase 3

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:

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 Design

Study Type:

Interventional

Anticipated Enrollment :

12942 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 13, 2020

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

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%
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%
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 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 21-30 %

Outcome Measures

Primary Outcome Measures

Number of participants with pneumonia using the US Centers for Disease Control (CDC) definition of pneumonia (Mouthwash intervention only) [Within 30 days post-surgery from index operation]
Pneumonia will be classified using the US Centers for Disease Control (CDC) definition of pneumonia
Number of participants with surgical site infection (Oxygen therapy intervention only) [Within 30 days post-surgery from index operation]
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

Secondary Outcome Measures

Number of trial participant moralities (Mouthwash and oxygen therapy intervention comparisons) [Within 30 days post-surgery from index operation]
Patient mortality status
Number of participants who received repeat abdominal surgery to treat complications (Oxygen therapy intervention only) [Within 30 days post-surgery from index operation]
Repeat abdominal surgery to treat complications
Number of participants who received repeat abdominal surgery (Mouthwash and oxygen therapy interventions) [Within 30 days post-surgery from index operation]
Repeat abdominal surgery
Length of hospital stay for index admission (Mouthwash and oxygen therapy interventions) [Within 30-days post surgery from index operation]
Length of hospital stay for index admission will be collected and will measure time from surgery to time of discharge.
Number of participants returning to normal activities (Mouthwash and oxygen therapy interventions) [Within 30 days post-surgery from index operation]
Return to normal activities (e.g. work, school, or family duties) ascertained by trial specific case report forms.
Number of participants admissions to a critical care unit (Mouthwash and oxygen therapy interventions) [Within 30 days post-surgery from index operation]
Admission to a critical care unit will be captured on the trial case report forms.
Health resource usage per patient [Within 30 days post-surgery from index operation]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)